WorldWideScience

Sample records for neural genome integrity

  1. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

    Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with DNA...

  2. Statistical Methods in Integrative Genomics

    OpenAIRE

    Richardson, Sylvia; Tseng, George C.; Sun, Wei

    2016-01-01

    Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and f...

  3. Histones and genome integrity.

    Science.gov (United States)

    Williamson, Wes D; Pinto, Ines

    2012-01-01

    Chromosomes undergo extensive structural rearrangements during the cell cycle, from the most open chromatin state required for DNA replication to the highest level of compaction and condensation essential for mitotic segregation of sister chromatids. It is now widely accepted that chromatin is a highly dynamic structure that participates in all DNA-related functions, including transcription, DNA replication, repair, and mitosis; hence, histones have emerged as key players in these cellular processes. We review here the studies that implicate histones in functions that affect the chromosome cycle, defined as the cellular processes involved in the maintenance, replication, and segregation of chromosomal DNA. Disruption of the chromosome cycle affects the integrity of the cellular genome, leading to aneuploidy, polyploidy or cell death. Histone stoichiometry, mutations that affect the structure of the nucleosome core particle, and mutations that affect the structure and/or modifications of the histone tails, all have a direct impact on the fidelity of chromosome transmission and the integrity of the genome.

  4. Probability landscapes for integrative genomics

    Directory of Open Access Journals (Sweden)

    Benecke Arndt

    2008-05-01

    Full Text Available Abstract Background The comprehension of the gene regulatory code in eukaryotes is one of the major challenges of systems biology, and is a requirement for the development of novel therapeutic strategies for multifactorial diseases. Its bi-fold degeneration precludes brute force and statistical approaches based on the genomic sequence alone. Rather, recursive integration of systematic, whole-genome experimental data with advanced statistical regulatory sequence predictions needs to be developed. Such experimental approaches as well as the prediction tools are only starting to become available and increasing numbers of genome sequences and empirical sequence annotations are under continual discovery-driven change. Furthermore, given the complexity of the question, a decade(s long multi-laboratory effort needs to be envisioned. These constraints need to be considered in the creation of a framework that can pave a road to successful comprehension of the gene regulatory code. Results We introduce here a concept for such a framework, based entirely on systematic annotation in terms of probability profiles of genomic sequence using any type of relevant experimental and theoretical information and subsequent cross-correlation analysis in hypothesis-driven model building and testing. Conclusion Probability landscapes, which include as reference set the probabilistic representation of the genomic sequence, can be used efficiently to discover and analyze correlations amongst initially heterogeneous and un-relatable descriptions and genome-wide measurements. Furthermore, this structure is usable as a support for automatically generating and testing hypotheses for alternative gene regulatory grammars and the evaluation of those through statistical analysis of the high-dimensional correlations between genomic sequence, sequence annotations, and experimental data. Finally, this structure provides a concrete and tangible basis for attempting to formulate a

  5. Impulsive Neural Networks Algorithm Based on the Artificial Genome Model

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2014-05-01

    Full Text Available To describe gene regulatory networks, this article takes the framework of the artificial genome model and proposes impulsive neural networks algorithm based on the artificial genome model. Firstly, the gene expression and the cell division tree are applied to generate spiking neurons with specific attributes, neural network structure, connection weights and specific learning rules of each neuron. Next, the gene segment duplications and divergence model are applied to design the evolutionary algorithm of impulsive neural networks at the level of the artificial genome. The dynamic changes of developmental gene regulatory networks are controlled during the whole evolutionary process. Finally, the behavior of collecting food for autonomous intelligent agent is simulated, which is driven by nerves. Experimental results demonstrate that the algorithm in this article has the evolutionary ability on large-scale impulsive neural networks

  6. The integrated microbial genome resource of analysis.

    Science.gov (United States)

    Checcucci, Alice; Mengoni, Alessio

    2015-01-01

    Integrated Microbial Genomes and Metagenomes (IMG) is a biocomputational system that allows to provide information and support for annotation and comparative analysis of microbial genomes and metagenomes. IMG has been developed by the US Department of Energy (DOE)-Joint Genome Institute (JGI). IMG platform contains both draft and complete genomes, sequenced by Joint Genome Institute and other public and available genomes. Genomes of strains belonging to Archaea, Bacteria, and Eukarya domains are present as well as those of viruses and plasmids. Here, we provide some essential features of IMG system and case study for pangenome analysis.

  7. Integrated Neural Flight and Propulsion Control System

    Science.gov (United States)

    Kaneshige, John; Gundy-Burlet, Karen; Norvig, Peter (Technical Monitor)

    2001-01-01

    This paper describes an integrated neural flight and propulsion control system. which uses a neural network based approach for applying alternate sources of control power in the presence of damage or failures. Under normal operating conditions, the system utilizes conventional flight control surfaces. Neural networks are used to provide consistent handling qualities across flight conditions and for different aircraft configurations. Under damage or failure conditions, the system may utilize unconventional flight control surface allocations, along with integrated propulsion control, when additional control power is necessary for achieving desired flight control performance. In this case, neural networks are used to adapt to changes in aircraft dynamics and control allocation schemes. Of significant importance here is the fact that this system can operate without emergency or backup flight control mode operations. An additional advantage is that this system can utilize, but does not require, fault detection and isolation information or explicit parameter identification. Piloted simulation studies were performed on a commercial transport aircraft simulator. Subjects included both NASA test pilots and commercial airline crews. Results demonstrate the potential for improving handing qualities and significantly increasing survivability rates under various simulated failure conditions.

  8. Integrated genome browser: visual analytics platform for genomics

    OpenAIRE

    2016-01-01

    Motivation: Genome browsers that support fast navigation through vast datasets and provide interactive visual analytics functions can help scientists achieve deeper insight into biological systems. Toward this end, we developed Integrated Genome Browser (IGB), a highly configurable, interactive and fast open source desktop genome browser. Results: Here we describe multiple updates to IGB, including all-new capabilities to display and interact with data from high-throughput sequencing experime...

  9. Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

    Science.gov (United States)

    Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

  10. Integrating genome assemblies with MAIA

    NARCIS (Netherlands)

    Nijkamp, J.F.; Winterbach, W.; Van den Broek, M.; Daran, J.M.; Reinders, M.J.T.; De Ridder, D.

    2010-01-01

    De novo assembly of a eukaryotic genome with next-generation sequencing data is still a challenging task. Over the past few years several assemblers have been developed, often suitable for one specific type of sequencing data. The number of known genomes is expanding rapidly, therefore it becomes po

  11. Identification of neural outgrowth genes using genome-wide RNAi.

    Directory of Open Access Journals (Sweden)

    Katharine J Sepp

    2008-07-01

    Full Text Available While genetic screens have identified many genes essential for neurite outgrowth, they have been limited in their ability to identify neural genes that also have earlier critical roles in the gastrula, or neural genes for which maternally contributed RNA compensates for gene mutations in the zygote. To address this, we developed methods to screen the Drosophila genome using RNA-interference (RNAi on primary neural cells and present the results of the first full-genome RNAi screen in neurons. We used live-cell imaging and quantitative image analysis to characterize the morphological phenotypes of fluorescently labelled primary neurons and glia in response to RNAi-mediated gene knockdown. From the full genome screen, we focused our analysis on 104 evolutionarily conserved genes that when downregulated by RNAi, have morphological defects such as reduced axon extension, excessive branching, loss of fasciculation, and blebbing. To assist in the phenotypic analysis of the large data sets, we generated image analysis algorithms that could assess the statistical significance of the mutant phenotypes. The algorithms were essential for the analysis of the thousands of images generated by the screening process and will become a valuable tool for future genome-wide screens in primary neurons. Our analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signalling molecules, enzymes, channels, receptors, and cytoskeletal proteins. We also found that genes known to be involved in protein and vesicle trafficking showed similar RNAi phenotypes. We confirmed phenotypes of the protein trafficking genes Sec61alpha and Ran GTPase using Drosophila embryo and mouse embryonic cerebral cortical neurons, respectively. Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new

  12. Neural and Cognitive Modeling with Networks of Leaky Integrator Units

    Science.gov (United States)

    Graben, Peter beim; Liebscher, Thomas; Kurths, Jürgen

    After reviewing several physiological findings on oscillations in the electroencephalogram (EEG) and their possible explanations by dynamical modeling, we present neural networks consisting of leaky integrator units as a universal paradigm for neural and cognitive modeling. In contrast to standard recurrent neural networks, leaky integrator units are described by ordinary differential equations living in continuous time. We present an algorithm to train the temporal behavior of leaky integrator networks by generalized back-propagation and discuss their physiological relevance. Eventually, we show how leaky integrator units can be used to build oscillators that may serve as models of brain oscillations and cognitive processes.

  13. Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Chen Jiun-Ching

    2007-05-01

    Full Text Available Abstract Background Genome-wide identification of specific oligonucleotides (oligos is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. Results We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes. Conclusion The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through

  14. Integrative bayesian network analysis of genomic data.

    Science.gov (United States)

    Ni, Yang; Stingo, Francesco C; Baladandayuthapani, Veerabhadran

    2014-01-01

    Rapid development of genome-wide profiling technologies has made it possible to conduct integrative analysis on genomic data from multiple platforms. In this study, we develop a novel integrative Bayesian network approach to investigate the relationships between genetic and epigenetic alterations as well as how these mutations affect a patient's clinical outcome. We take a Bayesian network approach that admits a convenient decomposition of the joint distribution into local distributions. Exploiting the prior biological knowledge about regulatory mechanisms, we model each local distribution as linear regressions. This allows us to analyze multi-platform genome-wide data in a computationally efficient manner. We illustrate the performance of our approach through simulation studies. Our methods are motivated by and applied to a multi-platform glioblastoma dataset, from which we reveal several biologically relevant relationships that have been validated in the literature as well as new genes that could potentially be novel biomarkers for cancer progression.

  15. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    Preserving genome integrity is essential for cell survival. To this end, mechanisms that supervise DNA replication and respond to replication perturbations have evolved. One such mechanism is the replication checkpoint, which responds to DNA replication stress and acts to ensure replication pausing...

  16. FUZZY NEURAL NETWORK FOR OBJECT IDENTIFICATION ON INTEGRATED CIRCUIT LAYOUTS

    Directory of Open Access Journals (Sweden)

    A. A. Doudkin

    2015-01-01

    Full Text Available Fuzzy neural network model based on neocognitron is proposed to identify layout objects on images of topological layers of integrated circuits. Testing of the model on images of real chip layouts was showed a highеr degree of identification of the proposed neural network in comparison to base neocognitron.

  17. Integr8 and Genome Reviews: integrated views of complete genomes and proteomes.

    Science.gov (United States)

    Kersey, Paul; Bower, Lawrence; Morris, Lorna; Horne, Alan; Petryszak, Robert; Kanz, Carola; Kanapin, Alexander; Das, Ujjwal; Michoud, Karine; Phan, Isabelle; Gattiker, Alexandre; Kulikova, Tamara; Faruque, Nadeem; Duggan, Karyn; Mclaren, Peter; Reimholz, Britt; Duret, Laurent; Penel, Simon; Reuter, Ingmar; Apweiler, Rolf

    2005-01-01

    Integr8 is a new web portal for exploring the biology of organisms with completely deciphered genomes. For over 190 species, Integr8 provides access to general information, recent publications, and a detailed statistical overview of the genome and proteome of the organism. The preparation of this analysis is supported through Genome Reviews, a new database of bacterial and archaeal DNA sequences in which annotation has been upgraded (compared to the original submission) through the integration of data from many sources, including the EMBL Nucleotide Sequence Database, the UniProt Knowledgebase, InterPro, CluSTr, GOA and HOGENOM. Integr8 also allows the users to customize their own interactive analysis, and to download both customized and prepared datasets for their own use. Integr8 is available at http://www.ebi.ac.uk/integr8.

  18. Integrative Genomics and Computational Systems Medicine

    Energy Technology Data Exchange (ETDEWEB)

    McDermott, Jason E.; Huang, Yufei; Zhang, Bing; Xu, Hua; Zhao, Zhongming

    2014-01-01

    The exponential growth in generation of large amounts of genomic data from biological samples has driven the emerging field of systems medicine. This field is promising because it improves our understanding of disease processes at the systems level. However, the field is still in its young stage. There exists a great need for novel computational methods and approaches to effectively utilize and integrate various omics data.

  19. Integrated Model of DNA Sequence Numerical Representation and Artificial Neural Network for Human Donor and Acceptor Sites Prediction

    Directory of Open Access Journals (Sweden)

    Mohammed Abo-Zahhad

    2014-07-01

    Full Text Available Human Genome Project has led to a huge inflow of genomic data. After the completion of human genome sequencing, more and more effort is being put into identification of splicing sites of exons and introns (donor and acceptor sites. These invite bioinformatics to analysis the genome sequences and identify the location of exon and intron boundaries or in other words prediction of splicing sites. Prediction of splice sites in genic regions of DNA sequence is one of the most challenging aspects of gene structure recognition. Over the last two decades, artificial neural networks gradually became one of the essential tools in bioinformatics. In this paper artificial neural networks with different numerical mapping techniques have been employed for building integrated model for splice site prediction in genes. An artificial neural network is trained and then used to find splice sites in human genes. A comparison between different mapping methods using trained neural network in terms of their precision in prediction of donor and acceptor sites will be presented in this paper. Training and measuring performance of neural network are carried out using sequences of the human genome (GRch37/hg19- chr21. Simulation results indicate that using Electron-Ion Interaction Potential numerical mapping method with neural network yields to the best performance in prediction.

  20. Event-driven neural integration and synchronicity in analog VLSI.

    Science.gov (United States)

    Yu, Theodore; Park, Jongkil; Joshi, Siddharth; Maier, Christoph; Cauwenberghs, Gert

    2012-01-01

    Synchrony and temporal coding in the central nervous system, as the source of local field potentials and complex neural dynamics, arises from precise timing relationships between spike action population events across neuronal assemblies. Recently it has been shown that coincidence detection based on spike event timing also presents a robust neural code invariant to additive incoherent noise from desynchronized and unrelated inputs. We present spike-based coincidence detection using integrate-and-fire neural membrane dynamics along with pooled conductance-based synaptic dynamics in a hierarchical address-event architecture. Within this architecture, we encode each synaptic event with parameters that govern synaptic connectivity, synaptic strength, and axonal delay with additional global configurable parameters that govern neural and synaptic temporal dynamics. Spike-based coincidence detection is observed and analyzed in measurements on a log-domain analog VLSI implementation of the integrate-and-fire neuron and conductance-based synapse dynamics.

  1. Integration of perception and reasoning in fast neural modules

    Science.gov (United States)

    Fritz, David G.

    1989-01-01

    Artificial neural systems promise to integrate symbolic and sub-symbolic processing to achieve real time control of physical systems. Two potential alternatives exist. In one, neural nets can be used to front-end expert systems. The expert systems, in turn, are developed with varying degrees of parallelism, including their implementation in neural nets. In the other, rule-based reasoning and sensor data can be integrated within a single hybrid neural system. The hybrid system reacts as a unit to provide decisions (problem solutions) based on the simultaneous evaluation of data and rules. Discussed here is a model hybrid system based on the fuzzy cognitive map (FCM). The operation of the model is illustrated with the control of a hypothetical satellite that intelligently alters its attitude in space in response to an intersecting micrometeorite shower.

  2. Flexible neural interfaces with integrated stiffening shank

    Science.gov (United States)

    Tooker, Angela C.; Felix, Sarah H.; Pannu, Satinderpall S.; Shah, Kedar G.; Sheth, Heeral; Tolosa, Vanessa

    2016-07-26

    A neural interface includes a first dielectric material having at least one first opening for a first electrical conducting material, a first electrical conducting material in the first opening, and at least one first interconnection trace electrical conducting material connected to the first electrical conducting material. A stiffening shank material is located adjacent the first dielectric material, the first electrical conducting material, and the first interconnection trace electrical conducting material.

  3. Integration of Unascertained Method with Neural Networks and Its Application

    Directory of Open Access Journals (Sweden)

    Huawang Shi

    2011-11-01

    Full Text Available This paper presents the adoption of artificial neural network (ANN model and Unascertained system to assist decision-makers in forecasting the early warning of financial in China. Artificial neural network (ANN has outstanding characteristics in machine learning, fault, tolerant, parallel reasoning and processing nonlinear problem abilities. Unascertained system that imitates the human brain's thinking logical is a kind of mathematical tools used to deal with imprecise and uncertain knowledge. Integrating unascertained method with neural network technology, the reasoning process of network coding can be tracked, and the output of the network can be given a physical explanation. Application case shows that combines unascertained systems with feedforward artificial neural networks can obtain more reasonable and more advantage of nonlinear mapping that can handle more complete type of data.

  4. Concept of neural genoarchitecture and its genomic fundament.

    Directory of Open Access Journals (Sweden)

    Luis ePuelles

    2012-11-01

    Full Text Available The recent concept of neural genoarchitecture (or genoarchitectonics is examined from several angles, aiming to clarify the rationale for this new approach in causal and descriptive neuroanatomy. Gene expression patterns can be used as topographic stains revealing architectonic borders that may clarify, dispute or complicate existing brain anatomical subdivisions based on other methods, while increasing our understanding of how they arise in ontogenesis and evolution. A section of the text deals with differential regulation of gene expression in an ontogenetic causal network, attending to the structure of the genome and the functional peculiarities of enhancer and repressor regulatory regions that modulate gene transcription. The emergence of regionally characteristic sets of active transcription factors represents a critical concept, molecular identity, which can be applied to discrete brain territories and neuronal populations. Gene regulation is tied to positional effects, that is, topologically invariant domains of gene expression and natural boundaries, which can be correlated with anatomic ones. The large-scale stability of these patterns among vertebrates underpins molecularly the structural brain Bauplan, and is the fundament of field homology. The study of genoarchitectonic boundaries is presented as a crucial objective of modern neuroanatomic research. At most brain regions, new neuronal populations are being detected thanks to their differential genoarchitectonic features.

  5. MycoCosm, an Integrated Fungal Genomics Resource

    Energy Technology Data Exchange (ETDEWEB)

    Shabalov, Igor; Grigoriev, Igor

    2012-03-16

    MycoCosm is a web-based interactive fungal genomics resource, which was first released in March 2010, in response to an urgent call from the fungal community for integration of all fungal genomes and analytical tools in one place (Pan-fungal data resources meeting, Feb 21-22, 2010, Alexandria, VA). MycoCosm integrates genomics data and analysis tools to navigate through over 100 fungal genomes sequenced at JGI and elsewhere. This resource allows users to explore fungal genomes in the context of both genome-centric analysis and comparative genomics, and promotes user community participation in data submission, annotation and analysis. MycoCosm has over 4500 unique visitors/month or 35000+ visitors/year as well as hundreds of registered users contributing their data and expertise to this resource. Its scalable architecture allows significant expansion of the data expected from JGI Fungal Genomics Program, its users, and integration with external resources used by fungal community.

  6. Classical Conditioning with Pulsed Integrated Neural Networks: Circuits and System

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    In this paper we investigate on-chip learning for pulsed, integrated neural networks. We discuss the implementational problems the technology imposes on learning systems and we find that abiologically inspired approach using simple circuit structures is most likely to bring success. We develop...... a suitable learning algorithm -- a continuous-time version of a temporal differential Hebbian learning algorithm for pulsed neural systems with non-linear synapses -- as well as circuits for the electronic implementation. Measurements from an experimental CMOS chip are presented. Finally, we use our test...

  7. Thermal photovoltaic solar integrated system analysis using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ashhab, S. [Hashemite Univ., Zarqa (Jordan). Dept. of Mechanical Engineering

    2007-07-01

    The energy demand in Jordan is primarily met by petroleum products. As such, the development of renewable energy systems is quite attractive. In particular, solar energy is a promising renewable energy source in Jordan and has been used for food canning, paper production, air-conditioning and sterilization. Artificial neural networks (ANNs) have received significant attention due to their capabilities in forecasting, modelling of complex nonlinear systems and control. ANNs have been used for forecasting solar energy. This paper presented a study that examined a thermal photovoltaic solar integrated system that was built in Jordan. Historical input-output system data that was collected experimentally was used to train an ANN that predicted the collector, PV module, pump and total efficiencies. The model predicted the efficiencies well and can therefore be utilized to find the operating conditions of the system that will produce the maximum system efficiencies. The paper provided a description of the photovoltaic solar system including equations for PV module efficiency; pump efficiency; and total efficiency. The paper also presented data relevant to the system performance and neural networks. The results of a neural net model were also presented based on the thermal PV solar integrated system data that was collected. It was concluded that the neural net model of the thermal photovoltaic solar integrated system set the background for achieving the best system performance. 10 refs., 6 figs.

  8. A model of interval timing by neural integration.

    Science.gov (United States)

    Simen, Patrick; Balci, Fuat; de Souza, Laura; Cohen, Jonathan D; Holmes, Philip

    2011-06-22

    We show that simple assumptions about neural processing lead to a model of interval timing as a temporal integration process, in which a noisy firing-rate representation of time rises linearly on average toward a response threshold over the course of an interval. Our assumptions include: that neural spike trains are approximately independent Poisson processes, that correlations among them can be largely cancelled by balancing excitation and inhibition, that neural populations can act as integrators, and that the objective of timed behavior is maximal accuracy and minimal variance. The model accounts for a variety of physiological and behavioral findings in rodents, monkeys, and humans, including ramping firing rates between the onset of reward-predicting cues and the receipt of delayed rewards, and universally scale-invariant response time distributions in interval timing tasks. It furthermore makes specific, well-supported predictions about the skewness of these distributions, a feature of timing data that is usually ignored. The model also incorporates a rapid (potentially one-shot) duration-learning procedure. Human behavioral data support the learning rule's predictions regarding learning speed in sequences of timed responses. These results suggest that simple, integration-based models should play as prominent a role in interval timing theory as they do in theories of perceptual decision making, and that a common neural mechanism may underlie both types of behavior.

  9. Analog VLSI neural network integrated circuits

    Science.gov (United States)

    Kub, F. J.; Moon, K. K.; Just, E. A.

    1991-01-01

    Two analog very large scale integration (VLSI) vector matrix multiplier integrated circuit chips were designed, fabricated, and partially tested. They can perform both vector-matrix and matrix-matrix multiplication operations at high speeds. The 32 by 32 vector-matrix multiplier chip and the 128 by 64 vector-matrix multiplier chip were designed to perform 300 million and 3 billion multiplications per second, respectively. An additional circuit that has been developed is a continuous-time adaptive learning circuit. The performance achieved thus far for this circuit is an adaptivity of 28 dB at 300 KHz and 11 dB at 15 MHz. This circuit has demonstrated greater than two orders of magnitude higher frequency of operation than any previous adaptive learning circuit.

  10. Comparative Genome Analysis in the Integrated Microbial Genomes(IMG) System

    Energy Technology Data Exchange (ETDEWEB)

    Kyrpides, Nikos C.; Markowitz, Victor M.

    2006-03-01

    Comparative genome analysis is critical for the effectiveexploration of a rapidly growing number of complete and draft sequencesfor microbial genomes. The Integrated Microbial Genomes (IMG) system(img.jgi.doe.gov) has been developed as a community resource thatprovides support for comparative analysis of microbial genomes in anintegrated context. IMG allows users to navigate the multidimensionalmicrobial genome data space and focus their analysis on a subset ofgenes, genomes, and functions of interest. IMG provides graphicalviewers, summaries and occurrence profile tools for comparing genes,pathways and functions (terms) across specific genomes. Genes can befurther examined using gene neighborhoods and compared with sequencealignment tools.

  11. Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch

    Directory of Open Access Journals (Sweden)

    London Sarah E

    2010-04-01

    Full Text Available Abstract Background Steroids are small molecule hormones derived from cholesterol. Steroids affect many tissues, including the brain. In the zebra finch, estrogenic steroids are particularly interesting because they masculinize the neural circuit that controls singing and their synthesis in the brain is modulated by experience. Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors. Based on these analyses, we also investigated neural expression of a cholesterol transport protein gene in the context of song neurobiology. Results We present sequence-based analysis of twenty steroid-related genes using the genome assembly and other resources. Generally, zebra finch genes showed high homology to genes in other species. The diversity of steroidogenic enzymes and receptors may be lower in songbirds than in mammals; we were unable to identify all known mammalian isoforms of the 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase families in the zebra finch genome assembly, and not all splice sites described in mammals were identified in the corresponding zebra finch genes. We did identify two factors, Nobox and NR1H2-RXR, that may be important for coordinated transcription of multiple steroid-related genes. We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO and steroidogenic acute regulatory protein (StAR. We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed. Also, transcription of TSPO, but not StAR, may be regulated by the experience of hearing song. Conclusions The genes required for estradiol synthesis and

  12. Herpesvirus Genome Integration into Telomeric Repeats of Host Cell Chromosomes.

    Science.gov (United States)

    Osterrieder, Nikolaus; Wallaschek, Nina; Kaufer, Benedikt B

    2014-11-01

    It is well known that numerous viruses integrate their genetic material into host cell chromosomes. Human herpesvirus 6 (HHV-6) and oncogenic Marek's disease virus (MDV) have been shown to integrate their genomes into host telomeres of latently infected cells. This is unusual for herpesviruses as most maintain their genomes as circular episomes during the quiescent stage of infection. The genomic DNA of HHV-6, MDV, and several other herpesviruses harbors telomeric repeats (TMRs) that are identical to host telomere sequences (TTAGGG). At least in the case of MDV, viral TMRs facilitate integration into host telomeres. Integration of HHV-6 occurs not only in lymphocytes but also in the germline of some individuals, allowing vertical virus transmission. Although the molecular mechanism of telomere integration is poorly understood, the presence of TMRs in a number of herpesviruses suggests it is their default program for genome maintenance during latency and also allows efficient reactivation.

  13. Wireless Neural Recording With Single Low-Power Integrated Circuit

    Science.gov (United States)

    Harrison, Reid R.; Kier, Ryan J.; Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V.

    2010-01-01

    We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6-μm 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902–928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor. PMID:19497825

  14. Wireless neural recording with single low-power integrated circuit.

    Science.gov (United States)

    Harrison, Reid R; Kier, Ryan J; Chestek, Cynthia A; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V

    2009-08-01

    We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902-928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor.

  15. Soft computing integrating evolutionary, neural, and fuzzy systems

    CERN Document Server

    Tettamanzi, Andrea

    2001-01-01

    Soft computing encompasses various computational methodologies, which, unlike conventional algorithms, are tolerant of imprecision, uncertainty, and partial truth. Soft computing technologies offer adaptability as a characteristic feature and thus permit the tracking of a problem through a changing environment. Besides some recent developments in areas like rough sets and probabilistic networks, fuzzy logic, evolutionary algorithms, and artificial neural networks are core ingredients of soft computing, which are all bio-inspired and can easily be combined synergetically. This book presents a well-balanced integration of fuzzy logic, evolutionary computing, and neural information processing. The three constituents are introduced to the reader systematically and brought together in differentiated combinations step by step. The text was developed from courses given by the authors and offers numerous illustrations as

  16. A System for Predicting Subcellular Localization of Yeast Genome Using Neural Network

    CERN Document Server

    Thampi, Sabu M

    2007-01-01

    The subcellular location of a protein can provide valuable information about its function. With the rapid increase of sequenced genomic data, the need for an automated and accurate tool to predict subcellular localization becomes increasingly important. Many efforts have been made to predict protein subcellular localization. This paper aims to merge the artificial neural networks and bioinformatics to predict the location of protein in yeast genome. We introduce a new subcellular prediction method based on a backpropagation neural network. The results show that the prediction within an error limit of 5 to 10 percentage can be achieved with the system.

  17. Perspectives of Integrative Cancer Genomics in Next Generation Sequencing Era

    Directory of Open Access Journals (Sweden)

    So Mee Kwon

    2012-06-01

    Full Text Available The explosive development of genomics technologies including microarrays and next generation sequencing (NGS has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

  18. Microbes Online: an integrated portal for comparative functional genomics

    OpenAIRE

    Arkin, Adam P.

    2014-01-01

    Since 2003, MicrobesOnline (http://www.microbesonline.org) has been providing a community resource for comparative and functional genome analysis. The portal includes over 1000 complete genomes of bacteria, archaea and fungi, as well as 1000s of viruses and plasmids. In addition to standard comparative genomic analysis, including gene prediction, sequence homology, domain identification, gene family assignments and functional annotations from E.C. and GO, MicrobesOnline integrates data from ...

  19. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

    Energy Technology Data Exchange (ETDEWEB)

    Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth; Wang, Victoria; Qi, Yuan; Wilkerson, Matthew D; Miller, C Ryan; Ding, Li; Golub, Todd; Mesirov, Jill P; Alexe, Gabriele; Lawrence, Michael; O' Kelly, Michael; Tamayo, Pablo; Weir, Barbara A; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Jakkula, Lakshmi; Feiler, Heidi S; Hodgson, J Graeme; James, C David; Sarkaria, Jann N; Brennan, Cameron; Kahn, Ari; Spellman, Paul T; Wilson, Richard K; Speed, Terence P; Gray, Joe W; Meyerson, Matthew; Getz, Gad; Perou, Charles M; Hayes, D Neil; Network, The Cancer Genome Atlas Research

    2009-09-03

    The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

  20. G-InforBIO: integrated system for microbial genomics

    Directory of Open Access Journals (Sweden)

    Abe Takashi

    2006-08-01

    Full Text Available Abstract Background Genome databases contain diverse kinds of information, including gene annotations and nucleotide and amino acid sequences. It is not easy to integrate such information for genomic study. There are few tools for integrated analyses of genomic data, therefore, we developed software that enables users to handle, manipulate, and analyze genome data with a variety of sequence analysis programs. Results The G-InforBIO system is a novel tool for genome data management and sequence analysis. The system can import genome data encoded as eXtensible Markup Language documents as formatted text documents, including annotations and sequences, from DNA Data Bank of Japan and GenBank encoded as flat files. The genome database is constructed automatically after importing, and the database can be exported as documents formatted with eXtensible Markup Language or tab-deliminated text. Users can retrieve data from the database by keyword searches, edit annotation data of genes, and process data with G-InforBIO. In addition, information in the G-InforBIO database can be analyzed seamlessly with nine different software programs, including programs for clustering and homology analyses. Conclusion The G-InforBIO system simplifies genome analyses by integrating several available software programs to allow efficient handling and manipulation of genome data. G-InforBIO is freely available from the download site.

  1. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jizhong; He, Zhili

    2014-04-08

    As a part of the Shewanella Federation project, we have used integrated genomic, proteomic and computational technologies to study various aspects of energy metabolism of two Shewanella strains from a systems-level perspective.

  2. Integrated proteomic and genomic analysis of colorectal cancer

    Science.gov (United States)

    Investigators who analyzed 95 human colorectal tumor samples have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, pro

  3. Neural correlates of audiovisual integration in music reading.

    Science.gov (United States)

    Nichols, Emily S; Grahn, Jessica A

    2016-10-01

    Integration of auditory and visual information is important to both language and music. In the linguistic domain, audiovisual integration alters event-related potentials (ERPs) at early stages of processing (the mismatch negativity (MMN)) as well as later stages (P300(Andres et al., 2011)). However, the role of experience in audiovisual integration is unclear, as reading experience is generally confounded with developmental stage. Here we tested whether audiovisual integration of music appears similar to reading, and how musical experience altered integration. We compared brain responses in musicians and non-musicians on an auditory pitch-interval oddball task that evoked the MMN and P300, while manipulating whether visual pitch-interval information was congruent or incongruent with the auditory information. We predicted that the MMN and P300 would be largest when both auditory and visual stimuli deviated, because audiovisual integration would increase the neural response when the deviants were congruent. The results indicated that scalp topography differed between musicians and non-musicians for both the MMN and P300 response to deviants. Interestingly, musicians' musical training modulated integration of congruent deviants at both early and late stages of processing. We propose that early in the processing stream, visual information may guide interpretation of auditory information, leading to a larger MMN when auditory and visual information mismatch. At later attentional stages, integration of the auditory and visual stimuli leads to a larger P300 amplitude. Thus, experience with musical visual notation shapes the way the brain integrates abstract sound-symbol pairings, suggesting that musicians can indeed inform us about the role of experience in audiovisual integration. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. From behavior to neural dynamics: An integrated theory of attention

    Science.gov (United States)

    Buschman, Timothy J.; Kastner, Sabine

    2015-01-01

    The brain has a limited capacity and therefore needs mechanisms to selectively enhance the information most relevant to one’s current behavior. We refer to these mechanisms as ‘attention’. Attention acts by increasing the strength of selected neural representations and preferentially routing them through the brain’s large-scale network. This is a critical component of cognition and therefore has been a central topic in cognitive neuroscience. Here we review a diverse literature that has studied attention at the level of behavior, networks, circuits and neurons. We then integrate these disparate results into a unified theory of attention. PMID:26447577

  5. An integrated modelling framework for neural circuits with multiple neuromodulators

    Science.gov (United States)

    Vemana, Vinith

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

  6. Using fuzzy logic to integrate neural networks and knowledge-based systems

    Science.gov (United States)

    Yen, John

    1991-01-01

    Outlined here is a novel hybrid architecture that uses fuzzy logic to integrate neural networks and knowledge-based systems. The author's approach offers important synergistic benefits to neural nets, approximate reasoning, and symbolic processing. Fuzzy inference rules extend symbolic systems with approximate reasoning capabilities, which are used for integrating and interpreting the outputs of neural networks. The symbolic system captures meta-level information about neural networks and defines its interaction with neural networks through a set of control tasks. Fuzzy action rules provide a robust mechanism for recognizing the situations in which neural networks require certain control actions. The neural nets, on the other hand, offer flexible classification and adaptive learning capabilities, which are crucial for dynamic and noisy environments. By combining neural nets and symbolic systems at their system levels through the use of fuzzy logic, the author's approach alleviates current difficulties in reconciling differences between low-level data processing mechanisms of neural nets and artificial intelligence systems.

  7. [Investigation on the integrative course of genetics and genomics].

    Science.gov (United States)

    Liu, Zhi-Xiang; Xu, Gang-Biao; Zeng, Chao-Zhen; Wang, Ai-Yun; Wu, Ruo-Yan

    2011-07-01

    Genomics is an important subdiscipline of genetics, and it forms a complete research system based on novel theories and techniques. Incorporating genomics in undergraduate curriculum is a response to the need of the development of genetics. The teaching of genomics has significant advantages on developing scientific thinking, enhances bioethics accomplishment, and professional interests in undergraduate students. The integration of genomics into genetics is in accordance with the principles of subject development and education. Related textbooks for undergraduate education are currently available in China, and it is feasible to set up a genetics and genomics integrative course by modifying teaching contents of the genetics course, selecting appropriate teaching approaches, and optimal application of the computer-assisted instruction.

  8. Genome-wide gene amplification during differentiation of neural progenitor cells in vitro.

    Science.gov (United States)

    Fischer, Ulrike; Keller, Andreas; Voss, Meike; Backes, Christina; Welter, Cornelius; Meese, Eckart

    2012-01-01

    DNA sequence amplification is a phenomenon that occurs predictably at defined stages during normal development in some organisms. Developmental gene amplification was first described in amphibians during gametogenesis and has not yet been described in humans. To date gene amplification in humans is a hallmark of many tumors. We used array-CGH (comparative genomic hybridization) and FISH (fluorescence in situ hybridization) to discover gene amplifications during in vitro differentiation of human neural progenitor cells. Here we report a complex gene amplification pattern two and five days after induction of differentiation of human neural progenitor cells. We identified several amplified genes in neural progenitor cells that are known to be amplified in malignant tumors. There is also a striking overlap of amplified chromosomal regions between differentiating neural progenitor cells and malignant tumor cells derived from astrocytes. Gene amplifications in normal human cells as physiological process has not been reported yet and may bear resemblance to developmental gene amplifications in amphibians and insects.

  9. Genome-wide screen for differential DNA methylation associated with neural cell differentiation in mouse.

    Directory of Open Access Journals (Sweden)

    Rene Cortese

    Full Text Available Cellular differentiation involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Using Differential Methylation Hybridization (DMH in combination with a custom DMH array containing 51,243 features covering more than 16,000 murine genes, we carried out a genome-wide screen for cell- and tissue-specific differentially methylated regions (tDMRs in undifferentiated embryonic stem cells (ESCs, in in-vitro induced neural stem cells (NSCs and 8 differentiated embryonic and adult tissues. Unsupervised clustering of the generated data showed distinct cell- and tissue-specific DNA methylation profiles, revealing 202 significant tDMRs (p1.96 enrichment for genes involved in neural differentiation, including, for example, Jag1 and Tcf4. Our results provide robust evidence for the relevance of DNA methylation in early neural development and identify novel marker candidates for neural cell differentiation.

  10. Integration of genomics in cancer care

    DEFF Research Database (Denmark)

    Santos, Erika Maria Monteiro; Edwards, Quannetta T; Floria-Santos, Milena

    2013-01-01

    cancer syndromes, epigenetics factors, and management of care considerations. METHODS: Peer-reviewed literature and expert professional guidelines were reviewed to address concepts of genetics-genomics in cancer care. FINDINGS: Cancer is now known to be heterogeneous at the molecular level, with genetic...

  11. Integrated genomic analyses of ovarian carcinoma

    NARCIS (Netherlands)

    Bell, D.; Berchuck, A.; Birrer, M.; Chien, J.; Dao, F.; Dhir, R.; DiSaia, P.; Gabra, H.; Glenn, P.; Godwin, A. K.; Gross, J.; Hartmann, L.; Huang, M.; Huntsman, D. G.; Iacocca, M.; Imielinski, M.; Kalloger, S.; Karlan, B. Y.; Levine, D. A.; Mills, G. B.; Morrison, C.; Mutch, D.; Olvera, N.; Orsulic, S.; Park, K.; Petrelli, N.; Rabeno, B.; Rader, J. S.; Sikic, B. I.; Smith-McCune, K.; Sood, A. K.; Bowtell, D.; Penny, R.; Testa, J. R.; Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Gunaratne, P.; Hawes, A. C.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Santibanez, J.; Reid, J. G.; Trevino, L. R.; Wu, Y. -Q.; Wang, M.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.; Getz, G.; Lawrence, M. S.; Cibulskis, K.; Sivachenko, A. Y.; Sougnez, C.; Voet, D.; Wilkinson, J.; Bloom, T.; Ardlie, K.; Fennell, T.; Baldwin, J.; Gabriel, S.; Lander, E. S.; Ding, L.; Fulton, R. S.; Koboldt, D. C.; McLellan, M. D.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D. J.; Fulton, L.; Abbott, R.; Dees, N. D.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C. C.; Schmidt, H.; Kalicki, J.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Cook, L.; Wallis, J. W.; Lin, L.; Magrini, V. J.; Hodges, J. S.; Eldred, J. M.; Smith, S. M.; Pohl, C. S.; Vandin, F.; Raphael, B. J.; Weinstock, G. M.; Mardis, R.; Wilson, R. K.; Meyerson, M.; Winckler, W.; Getz, G.; Verhaak, R. G. W.; Carter, S. L.; Mermel, C. H.; Saksena, G.; Nguyen, H.; Onofrio, R. C.; Lawrence, M. S.; Hubbard, D.; Gupta, S.; Crenshaw, A.; Ramos, A. H.; Ardlie, K.; Chin, L.; Protopopov, A.; Zhang, Juinhua; Kim, T. M.; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Sathiamoorthy, N.; Park, R. W.; Lee, E.; Park, P. J.; Kucherlapati, R.; Absher, D. M.; Waite, L.; Sherlock, G.; Brooks, J. D.; Li, J. Z.; Xu, J.; Myers, R. M.; Laird, P. W.; Cope, L.; Herman, J. G.; Shen, H.; Weisenberger, D. J.; Noushmehr, H.; Pan, F.; Triche, T.; Berman, B. P.; Van den Berg, D. J.; Buckley, J.; Baylin, S. B.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Jakkula, L. R.; Durinck, S.; Han, J.; Dorton, S.; Marr, H.; Choi, Y. G.; Wang, V.; Wang, N. J.; Ngai, J.; Conboy, J. G.; Parvin, B.; Feiler, H. S.; Speed, T. P.; Gray, J. W.; Levine, D. A.; Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Borsu, L.; Lash, A. E.; Brennan, C.; Viale, A.; Sander, C.; Ladanyi, M.; Hoadley, K. A.; Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y. J.; Zang, D.; Helms, E. B.; Balu, S.; Zhou, X.; Wu, J.; Topal, M. D.; Hayes, D. N.; Perou, C. M.; Getz, G.; Voet, D.; Saksena, G.; Zhang, Junihua; Zhang, H.; Wu, C. J.; Shukla, S.; Cibulskis, K.; Lawrence, M. S.; Sivachenko, A.; Jing, R.; Park, R. W.; Liu, Y.; Park, P. J.; Noble, M.; Chin, L.; Carter, H.; Kim, D.; Karchin, R.; Spellman, P. T.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Durinck, S.; Han, J.; Korkola, J. E.; Heiser, L. M.; Cho, R. J.; Hu, Z.; Parvin, B.; Speed, T. P.; Gray, J. W.; Schultz, N.; Cerami, E.; Taylor, B. S.; Olshen, A.; Reva, B.; Antipin, Y.; Shen, R.; Mankoo, P.; Sheridan, R.; Ciriello, G.; Chang, W. K.; Bernanke, J. A.; Borsu, L.; Levine, D. A.; Ladanyi, M.; Sander, C.; Haussler, D.; Benz, C. C.; Stuart, J. M.; Benz, S. C.; Sanborn, J. Z.; Vaske, C. J.; Zhu, J.; Szeto, C.; Scott, G. K.; Yau, C.; Hoadley, K. A.; Du, Y.; Balu, S.; Hayes, D. N.; Perou, C. M.; Wilkerson, M. D.; Zhang, N.; Akbani, R.; Baggerly, K. A.; Yung, W. K.; Mills, G. B.; Weinstein, J. N.; Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.; Kahn, A.; Greene, J. M.; Sfeir, R.; Jensen, M. A.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.; Zhang, Jinghui; Barker, A.; Compton, C.; Eley, G.; Ferguson, M.; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Shaw, K. R. Mills; Vaught, J.; Vockley, J. B.; Good, P. J.; Guyer, M. S.; Ozenberger, B.; Peterson, J.; Thomson, E.; Cramer, D.W.

    2011-01-01

    A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade

  12. Attention Modulates the Neural Processes Underlying Multisensory Integration of Emotion

    Directory of Open Access Journals (Sweden)

    Hao Tam Ho

    2011-10-01

    Full Text Available Integrating emotional information from multiple sensory modalities is generally assumed to be a pre-attentive process (de Gelder et al., 1999. This assumption, however, presupposes that the integrative process occurs independent of attention. Using event-potentials (ERP the present study investigated whether the neural processes underlying the integration of dynamic facial expression and emotional prosody is indeed unaffected by attentional manipulations. To this end, participants were presented with congruent and incongruent face-voice combinations (eg, an angry face combined with a neutral voice and performed different two-choice tasks in four consecutive blocks. Three of the tasks directed the participants' attention to emotion expressions in the face, the voice or both. The fourth task required participants to attend to the synchronicity between voice and lip movements. The results show divergent modulations of early ERP components by the different attentional manipulations. For example, when attention was directed to the face (or the voice, incongruent stimuli elicited a reduced N1 as compared to congruent stimuli. This effect was absent, when attention was diverted away from the emotionality in both face and voice suggesting that the detection of emotional incongruence already requires attention. Based on these findings, we question whether multisensory integration of emotion occurs indeed pre-attentively.

  13. An Integrative Breakage Model of genome architecture, reshuffling and evolution: The Integrative Breakage Model of genome evolution, a novel multidisciplinary hypothesis for the study of genome plasticity.

    Science.gov (United States)

    Farré, Marta; Robinson, Terence J; Ruiz-Herrera, Aurora

    2015-05-01

    Our understanding of genomic reorganization, the mechanics of genomic transmission to offspring during germ line formation, and how these structural changes contribute to the speciation process, and genetic disease is far from complete. Earlier attempts to understand the mechanism(s) and constraints that govern genome remodeling suffered from being too narrowly focused, and failed to provide a unified and encompassing view of how genomes are organized and regulated inside cells. Here, we propose a new multidisciplinary Integrative Breakage Model for the study of genome evolution. The analysis of the high-level structural organization of genomes (nucleome), together with the functional constrains that accompany genome reshuffling, provide insights into the origin and plasticity of genome organization that may assist with the detection and isolation of therapeutic targets for the treatment of complex human disorders. © 2015 WILEY Periodicals, Inc.

  14. STINGRAY: system for integrated genomic resources and analysis

    OpenAIRE

    Wagner, Glauber; Jardim, Rodrigo; Tschoeke, Diogo A; Loureiro, Daniel R.; Ocaña, Kary ACS; Ribeiro, Antonio CB; Vanessa E. Emmel; Probst, Christian M.; Pitaluga, André N; Grisard, Edmundo C; Cavalcanti, Maria C; Campos, Maria LM; Mattoso, Marta; Dávila, Alberto MR

    2014-01-01

    Background The STINGRAY system has been conceived to ease the tasks of integrating, analyzing, annotating and presenting genomic and expression data from Sanger and Next Generation Sequencing (NGS) platforms. Findings STINGRAY includes: (a) a complete and integrated workflow (more than 20 bioinformatics tools) ranging from functional annotation to phylogeny; (b) a MySQL database schema, suitable for data integration and user access control; and (c) a user-friendly graphical web-based interfac...

  15. Defining nephrotic syndrome from an integrative genomics perspective.

    Science.gov (United States)

    Sampson, Matthew G; Hodgin, Jeffrey B; Kretzler, Matthias

    2015-01-01

    Nephrotic syndrome (NS) is a clinical condition with a high degree of morbidity and mortality, caused by failure of the glomerular filtration barrier, resulting in massive proteinuria. Our current diagnostic, prognostic and therapeutic decisions in NS are largely based upon clinical or histological patterns such as "focal segmental glomerulosclerosis" or "steroid sensitive". Yet these descriptive classifications lack the precision to explain the physiologic origins and clinical heterogeneity observed in this syndrome. A more precise definition of NS is required to identify mechanisms of disease and capture various clinical trajectories. An integrative genomics approach to NS applies bioinformatics and computational methods to comprehensive experimental, molecular and clinical data for holistic disease definition. A unique aspect is analysis of data together to discover NS-associated molecules, pathways, and networks. Integrating multidimensional datasets from the outset highlights how molecular lesions impact the entire individual. Data sets integrated range from genetic variation to gene expression, to histologic changes, to progression of chronic kidney disease (CKD). This review will introduce the tenets of integrative genomics and suggest how it can increase our understanding of NS from molecular and pathophysiological perspectives. A diverse group of genome-scale experiments are presented that have sought to define molecular signatures of NS. Finally, the Nephrotic Syndrome Study Network (NEPTUNE) will be introduced as an international, prospective cohort study of patients with NS that utilizes an integrated systems genomics approach from the outset. A major NEPTUNE goal is to achieve comprehensive disease definition from a genomics perspective and identify shared molecular drivers of disease.

  16. Integrative modules for efficient genome engineering in yeast

    Directory of Open Access Journals (Sweden)

    Triana Amen

    2017-06-01

    Full Text Available We present a set of vectors containing integrative modules for efficient genome integration into the commonly used selection marker loci of the yeast Saccharomyces cerevisiae. A fragment for genome integration is generated via PCR with a unique set of short primers and integrated into HIS3, URA3, ADE2, and TRP1 loci. The desired level of expression can be achieved by using constitutive (TEF1p, GPD1p, inducible (CUP1p, GAL1/10p, and daughter-specific (DSE4p promoters available in the modules. The reduced size of the integrative module compared to conventional integrative plasmids allows efficient integration of multiple fragments. We demonstrate the efficiency of this tool by simultaneously tagging markers of the nucleus, vacuole, actin, and peroxisomes with genomically integrated fluorophores. Improved integration of our new pDK plasmid series allows stable introduction of several genes and can be used for multi-color imaging. New bidirectional promoters (TEF1p-GPD1p, TEF1p-CUP1p, and TEF1p-DSE4p allow tractable metabolic engineering.

  17. Transgene directionally integrated into C-genome of Brassica napus

    Institute of Scientific and Technical Information of China (English)

    FANG Xiaoping; WANG Zhuan; LI Jun; LUO Lixia; HU Qiong

    2006-01-01

    Integration of a transgene into a C-genome chromosome plays an important role in reducing ecological risk of transgenic Brassica napus.To obtain C-genome transgenic B. napus, herbicide-resistant bar gene was firstly transferred into B.oleracea var. a/bog/abra mediated by Agrobacterium tumefaciens strain LBA4404. Then using the transgenic B. oleracea as paternal plants and 8 nontransgenic varieties of B. rapa as maternal plants, Cgenome transgenic B. napus with bar gene was artificially resynthesized by means of ovary culture and chromosome doubling. Among 67 lines of the resynthesized B. napus, 31 were positive, and 36 were negative according to PCR test for bar gene. At least 2 plants from each line were kept for PPT spray confirmation. The result was in consistence with the PCR test. Genomic Southern blotting of three randomly chosen lines also showed that bar gene had been integrated into the genome of resynthesized B. napus lines.

  18. Neural Networks Integrated Circuit for Biomimetics MEMS Microrobot

    Directory of Open Access Journals (Sweden)

    Ken Saito

    2014-06-01

    Full Text Available In this paper, we will propose the neural networks integrated circuit (NNIC which is the driving waveform generator of the 4.0, 2.7, 2.5 mm, width, length, height in size biomimetics microelectromechanical systems (MEMS microrobot. The microrobot was made from silicon wafer fabricated by micro fabrication technology. The mechanical system of the robot was equipped with small size rotary type actuators, link mechanisms and six legs to realize the ant-like switching behavior. The NNIC generates the driving waveform using synchronization phenomena such as biological neural networks. The driving waveform can operate the actuators of the MEMS microrobot directly. Therefore, the NNIC bare chip realizes the robot control without using any software programs or A/D converters. The microrobot performed forward and backward locomotion, and also changes direction by inputting an external single trigger pulse. The locomotion speed of the microrobot was 26.4 mm/min when the step width was 0.88 mm. The power consumption of the system was 250 mWh when the room temperature was 298 K.

  19. A neural circuit architecture for angular integration in Drosophila.

    Science.gov (United States)

    Green, Jonathan; Adachi, Atsuko; Shah, Kunal K; Hirokawa, Jonathan D; Magani, Pablo S; Maimon, Gaby

    2017-06-01

    Many animals keep track of their angular heading over time while navigating through their environment. However, a neural-circuit architecture for computing heading has not been experimentally defined in any species. Here we describe a set of clockwise- and anticlockwise-shifting neurons in the Drosophila central complex whose wiring and physiology provide a means to rotate an angular heading estimate based on the fly's angular velocity. We show that each class of shifting neurons exists in two subtypes, with spatiotemporal activity profiles that suggest different roles for each subtype at the start and end of tethered-walking turns. Shifting neurons are required for the heading system to properly track the fly's heading in the dark, and stimulation of these neurons induces predictable shifts in the heading signal. The central features of this biological circuit are analogous to those of computational models proposed for head-direction cells in rodents and may shed light on how neural systems, in general, perform integration.

  20. Overview of the Integrated Genomic Data system (IGD)

    Energy Technology Data Exchange (ETDEWEB)

    Hagstrom, R.; Overbeek, R.; Price, M. (Argonne National Lab., IL (United States)); Micheals, G.S.; Taylor, R. (National Insts. of Health, Bethesda, MD (United States). Div. of Computer Resources and Technology)

    1992-01-01

    In previous work, we developed a database system to support analysis of the E. coli genome. That system provided a pidgin-English query facility, rudimentary pattern-matching capabilities, and the ability to rapidly extract answers to a wide variety of questions about the organization of the E. coli genome. To enable the comparative analysis of the genomes from different species, we have designed and implemented a new prototype database system, called the Integrated Genomic Database (IGD). IGD extends our earlier effort by incorporating a set of curator's tools that facilitate the incorporation of physical and genetic data, together with the results of genome organization analysis, into a common database system. Additional tools for extracting, manipulating, and analyzing data are planned.

  1. Overview of the Integrated Genomic Data system (IGD)

    Energy Technology Data Exchange (ETDEWEB)

    Hagstrom, R.; Overbeek, R.; Price, M. [Argonne National Lab., IL (United States); Micheals, G.S.; Taylor, R. [National Insts. of Health, Bethesda, MD (United States). Div. of Computer Resources and Technology

    1992-12-01

    In previous work, we developed a database system to support analysis of the E. coli genome. That system provided a pidgin-English query facility, rudimentary pattern-matching capabilities, and the ability to rapidly extract answers to a wide variety of questions about the organization of the E. coli genome. To enable the comparative analysis of the genomes from different species, we have designed and implemented a new prototype database system, called the Integrated Genomic Database (IGD). IGD extends our earlier effort by incorporating a set of curator`s tools that facilitate the incorporation of physical and genetic data, together with the results of genome organization analysis, into a common database system. Additional tools for extracting, manipulating, and analyzing data are planned.

  2. Improving microbial genome annotations in an integrated database context.

    Directory of Open Access Journals (Sweden)

    I-Min A Chen

    Full Text Available Effective comparative analysis of microbial genomes requires a consistent and complete view of biological data. Consistency regards the biological coherence of annotations, while completeness regards the extent and coverage of functional characterization for genomes. We have developed tools that allow scientists to assess and improve the consistency and completeness of microbial genome annotations in the context of the Integrated Microbial Genomes (IMG family of systems. All publicly available microbial genomes are characterized in IMG using different functional annotation and pathway resources, thus providing a comprehensive framework for identifying and resolving annotation discrepancies. A rule based system for predicting phenotypes in IMG provides a powerful mechanism for validating functional annotations, whereby the phenotypic traits of an organism are inferred based on the presence of certain metabolic reactions and pathways and compared to experimentally observed phenotypes. The IMG family of systems are available at http://img.jgi.doe.gov/.

  3. MicrobesOnline: an integrated portal for comparative functional genomics

    OpenAIRE

    Joachimiak, Marcin P.

    2014-01-01

    The Virtual Institute for Microbial Stress and Survival (VIMSS, http://vimss.lbl.gov/) funded by the Dept. of Energy's Genomics:GTL Program, is dedicated to using integrated environmental, functional genomic, and comparative sequence and phylogeny data to understand mechanisms by which microbes and microbial communities survive in uncertain environments while carrying out processes of interest for bioremediation and energy generation. To support this work, VIMSS has developed a Web portal, al...

  4. IMGD: an integrated platform supporting comparative genomics and phylogenetics of insect mitochondrial genomes

    Directory of Open Access Journals (Sweden)

    Jung Kyongyong

    2009-04-01

    Full Text Available Abstract Background Sequences and organization of the mitochondrial genome have been used as markers to investigate evolutionary history and relationships in many taxonomic groups. The rapidly increasing mitochondrial genome sequences from diverse insects provide ample opportunities to explore various global evolutionary questions in the superclass Hexapoda. To adequately support such questions, it is imperative to establish an informatics platform that facilitates the retrieval and utilization of available mitochondrial genome sequence data. Results The Insect Mitochondrial Genome Database (IMGD is a new integrated platform that archives the mitochondrial genome sequences from 25,747 hexapod species, including 112 completely sequenced and 20 nearly completed genomes and 113,985 partially sequenced mitochondrial genomes. The Species-driven User Interface (SUI of IMGD supports data retrieval and diverse analyses at multi-taxon levels. The Phyloviewer implemented in IMGD provides three methods for drawing phylogenetic trees and displays the resulting trees on the web. The SNP database incorporated to IMGD presents the distribution of SNPs and INDELs in the mitochondrial genomes of multiple isolates within eight species. A newly developed comparative SNU Genome Browser supports the graphical presentation and interactive interface for the identified SNPs/INDELs. Conclusion The IMGD provides a solid foundation for the comparative mitochondrial genomics and phylogenetics of insects. All data and functions described here are available at the web site http://www.imgd.org/.

  5. Leader neurons in leaky integrate and fire neural network simulations.

    Science.gov (United States)

    Zbinden, Cyrille

    2011-10-01

    In this paper, we highlight the topological properties of leader neurons whose existence is an experimental fact. Several experimental studies show the existence of leader neurons in population bursts of activity in 2D living neural networks (Eytan and Marom, J Neurosci 26(33):8465-8476, 2006; Eckmann et al., New J Phys 10(015011), 2008). A leader neuron is defined as a neuron which fires at the beginning of a burst (respectively network spike) more often than we expect by chance considering its mean firing rate. This means that leader neurons have some burst triggering power beyond a chance-level statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate neural 2D networks. To build our simulations, we choose the leaky integrate and fire (lIF) neuron model (Gerstner and Kistler 2002; Cessac, J Math Biol 56(3):311-345, 2008), which allows fast simulations (Izhikevich, IEEE Trans Neural Netw 15(5):1063-1070, 2004; Gerstner and Naud, Science 326:379-380, 2009). The dynamics of our lIF model has got stable leader neurons in the burst population that we simulate. These leader neurons are excitatory neurons and have a low membrane potential firing threshold. Except for these two first properties, the conditions required for a neuron to be a leader neuron are difficult to identify and seem to depend on several parameters involved in the simulations themselves. However, a detailed linear analysis shows a trend of the properties required for a neuron to be a leader neuron. Our main finding is: A leader neuron sends signals to many excitatory neurons as well as to few inhibitory neurons and a leader neuron receives only signals from few other excitatory neurons. Our linear analysis exhibits five essential properties of leader neurons each with different relative importance. This means that considering a given neural network with a fixed mean number of connections per neuron, our analysis gives us a way of

  6. SIGMA: A System for Integrative Genomic Microarray Analysis of Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Davies Jonathan J

    2006-12-01

    Full Text Available Abstract Background The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. Results We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. Conclusion In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA of cancer genomes, can be accessed at http://sigma.bccrc.ca.

  7. Integrated Genomic Characterization of Papillary Thyroid Carcinoma

    Science.gov (United States)

    Agrawal, Nishant; Akbani, Rehan; Aksoy, B. Arman; Ally, Adrian; Arachchi, Harindra; Asa, Sylvia L.; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B.; Behera, Madhusmita; Bernard, Brady; Beroukhim, Rameen; Bishop, Justin A.; Black, Aaron D.; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Bowlby, Reanne; Bristow, Christopher A.; Brookens, Robin; Brooks, Denise; Bryant, Robert; Buda, Elizabeth; Butterfield, Yaron S.N.; Carling, Tobias; Carlsen, Rebecca; Carter, Scott L.; Carty, Sally E.; Chan, Timothy A.; Chen, Amy Y.; Cherniack, Andrew D.; Cheung, Dorothy; Chin, Lynda; Cho, Juok; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Ciriello, Giovanni; Clarke, Amanda; Clayman, Gary L.; Cope, Leslie; Copland, John; Covington, Kyle; Danilova, Ludmila; Davidsen, Tanja; Demchok, John A.; DiCara, Daniel; Dhalla, Noreen; Dhir, Rajiv; Dookran, Sheliann S.; Dresdner, Gideon; Eldridge, Jonathan; Eley, Greg; El-Naggar, Adel K.; Eng, Stephanie; Fagin, James A.; Fennell, Timothy; Ferris, Robert L.; Fisher, Sheila; Frazer, Scott; Frick, Jessica; Gabriel, Stacey B.; Ganly, Ian; Gao, Jianjiong; Garraway, Levi A.; Gastier-Foster, Julie M.; Getz, Gad; Gehlenborg, Nils; Ghossein, Ronald; Gibbs, Richard A.; Giordano, Thomas J.; Gomez-Hernandez, Karen; Grimsby, Jonna; Gross, Benjamin; Guin, Ranabir; Hadjipanayis, Angela; Harper, Hollie A.; Hayes, D. Neil; Heiman, David I.; Herman, James G.; Hoadley, Katherine A.; Hofree, Matan; Holt, Robert A.; Hoyle, Alan P.; Huang, Franklin W.; Huang, Mei; Hutter, Carolyn M.; Ideker, Trey; Iype, Lisa; Jacobsen, Anders; Jefferys, Stuart R.; Jones, Corbin D.; Jones, Steven J.M.; Kasaian, Katayoon; Kebebew, Electron; Khuri, Fadlo R.; Kim, Jaegil; Kramer, Roger; Kreisberg, Richard; Kucherlapati, Raju; Kwiatkowski, David J.; Ladanyi, Marc; Lai, Phillip H.; Laird, Peter W.; Lander, Eric; Lawrence, Michael S.; Lee, Darlene; Lee, Eunjung; Lee, Semin; Lee, William; Leraas, Kristen M.; Lichtenberg, Tara M.; Lichtenstein, Lee; Lin, Pei; Ling, Shiyun; Liu, Jinze; Liu, Wenbin; Liu, Yingchun; LiVolsi, Virginia A.; Lu, Yiling; Ma, Yussanne; Mahadeshwar, Harshad S.; Marra, Marco A.; Mayo, Michael; McFadden, David G.; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Miller, Michael; Mills, Gordon; Moore, Richard A.; Mose, Lisle E.; Mungall, Andrew J.; Murray, Bradley A.; Nikiforov, Yuri E.; Noble, Michael S.; Ojesina, Akinyemi I.; Owonikoko, Taofeek K.; Ozenberger, Bradley A.; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J.; Parker, Joel S.; Paull, Evan O.; Pedamallu, Chandra Sekhar; Perou, Charles M.; Prins, Jan F.; Protopopov, Alexei; Ramalingam, Suresh S.; Ramirez, Nilsa C.; Ramirez, Ricardo; Raphael, Benjamin J.; Rathmell, W. Kimryn; Ren, Xiaojia; Reynolds, Sheila M.; Rheinbay, Esther; Ringel, Matthew D.; Rivera, Michael; Roach, Jeffrey; Robertson, A. Gordon; Rosenberg, Mara W.; Rosenthall, Matthew; Sadeghi, Sara; Saksena, Gordon; Sander, Chris; Santoso, Netty; Schein, Jacqueline E.; Schultz, Nikolaus; Schumacher, Steven E.; Seethala, Raja R.; Seidman, Jonathan; Senbabaoglu, Yasin; Seth, Sahil; Sharpe, Samantha; Mills Shaw, Kenna R.; Shen, John P.; Shen, Ronglai; Sherman, Steven; Sheth, Margi; Shi, Yan; Shmulevich, Ilya; Sica, Gabriel L.; Simons, Janae V.; Sipahimalani, Payal; Smallridge, Robert C.; Sofia, Heidi J.; Soloway, Matthew G.; Song, Xingzhi; Sougnez, Carrie; Stewart, Chip; Stojanov, Petar; Stuart, Joshua M.; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Tarnuzzer, Roy; Taylor, Barry S.; Thiessen, Nina; Thorne, Leigh; Thorsson, Vésteinn; Tuttle, R. Michael; Umbricht, Christopher B.; Van Den Berg, David J.; Vandin, Fabio; Veluvolu, Umadevi; Verhaak, Roel G.W.; Vinco, Michelle; Voet, Doug; Walter, Vonn; Wang, Zhining; Waring, Scot; Weinberger, Paul M.; Weinstein, John N.; Weisenberger, Daniel J.; Wheeler, David; Wilkerson, Matthew D.; Wilson, Jocelyn; Williams, Michelle; Winer, Daniel A.; Wise, Lisa; Wu, Junyuan; Xi, Liu; Xu, Andrew W.; Yang, Liming; Yang, Lixing; Zack, Travis I.; Zeiger, Martha A.; Zeng, Dong; Zenklusen, Jean Claude; Zhao, Ni; Zhang, Hailei; Zhang, Jianhua; Zhang, Jiashan (Julia); Zhang, Wei; Zmuda, Erik; Zou., Lihua

    2014-01-01

    Summary Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease. PMID:25417114

  8. Repetitive genomic sequences as a substrate for homologous integration in the Rhizopus oryzae genome.

    Science.gov (United States)

    Yuzbashev, Tigran V; Larina, Anna S; Vybornaya, Tatiana V; Yuzbasheva, Evgeniya Y; Gvilava, Ilia T; Sineoky, Sergey P

    2015-06-01

    The vast number of repetitive genomic elements was identified in the genome of Rhizopus oryzae. Such genomic repeats can be used as homologous regions for integration of plasmids. Here, we evaluated the use of two different repeats: the short (575 bp) rptZ, widely distributed (about 34 copies per genome) and the long (2053 bp) rptH, less prevalent (about 15 copies). The plasmid carrying rptZ integrated, but did so through a 2256-bp region of homology to the pyrG locus, a unique genomic sequence. Thus, the length of rptZ was below the minimal requirements for homologous strand exchange in this fungus. In contrast, rptH was used efficiently for homologous integration. The plasmid bearing this repeat integrated in multicopy fashion, with up to 25 copies arranged in tandem. The latter vector, pPyrG-H, could be a valuable tool for integration at homologous sequences, for such purposes as high-level expression of proteins. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  9. Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace

    Science.gov (United States)

    Thorvaldsdottir, Helga; Liefeld, Ted; Ocana, Marco; Borges-Rivera, Diego; Pochet, Nathalie; Robinson, James T.; Demchak, Barry; Hull, Tim; Ben-Artzi, Gil; Blankenberg, Daniel; Barber, Galt P.; Lee, Brian T.; Kuhn, Robert M.; Nekrutenko, Anton; Segal, Eran; Ideker, Trey; Reich, Michael; Regev, Aviv; Chang, Howard Y.; Mesirov, Jill P.

    2015-01-01

    Integrative analysis of multiple data types to address complex biomedical questions requires the use of multiple software tools in concert and remains an enormous challenge for most of the biomedical research community. Here we introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource. Seeded as a collaboration of six of the most popular genomics analysis tools, GenomeSpace now supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate the ability of non-programming users’ to leverage GenomeSpace in integrative analysis, it offers a growing set of ‘recipes’, short workflows involving a few tools and steps to guide investigators through high utility analysis tasks. PMID:26780094

  10. Functional integration of human neural precursor cells in mouse cortex.

    Directory of Open Access Journals (Sweden)

    Fu-Wen Zhou

    Full Text Available This study investigates the electrophysiological properties and functional integration of different phenotypes of transplanted human neural precursor cells (hNPCs in immunodeficient NSG mice. Postnatal day 2 mice received unilateral injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks after transplantation, 1.21% of transplanted hNPCs survived. In these hNPCs, parvalbumin (PV-, calretinin (CR-, somatostatin (SS-positive inhibitory interneurons and excitatory pyramidal neurons were confirmed electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive with anti-human specific nuclear protein. The proportions of PV-, CR-, and SS-positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively; around 15% of GFP+ cells were identified as pyramidal neurons. Those electrophysiologically and histological identified GFP+ hNPCs were shown to fire action potentials with the appropriate firing patterns for different classes of neurons and to display spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs. The amplitude, frequency and kinetic properties of sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to integrate functionally into host neocortical neuronal networks. This provides promising data on the potential for hNPCs to serve as therapeutic agents in neurological diseases with abnormal neuronal circuitry such as epilepsy.

  11. Transcriptional and Genomic Targets of Neural Stem Cells for Functional Recovery after Hemorrhagic Stroke

    Directory of Open Access Journals (Sweden)

    Le Zhang

    2017-01-01

    Full Text Available Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of cerebral blood vessels, and it is widely believed that neural cell death occurs after exposure to blood metabolites or subsequently damaged cells. Neural stem cells (NSCs, which maintain neurogenesis and are found in subgranular zone and subventricular zone, are thought to be an endogenous neuroprotective mechanism for these brain injuries. However, due to the complexity of NSCs and their microenvironment, current strategies cannot satisfactorily enhance functional recovery after hemorrhagic stroke. It is well known that transcriptional and genomic pathways play important roles in ensuring the normal functions of NSCs, including proliferation, migration, differentiation, and neural reconnection. Recently, emerging evidence from the use of new technologies such as next-generation sequencing and transcriptome profiling has provided insight into our understanding of genomic function and regulation of NSCs. In the present article, we summarize and present the current data on the control of NSCs at both the transcriptional and genomic levels. Using bioinformatics methods, we sought to predict novel therapeutic targets of endogenous neurogenesis and exogenous NSC transplantation for functional recovery after hemorrhagic stroke, which could also advance our understanding of its pathophysiology.

  12. Integrative pathway genomics of lung function and airflow obstruction

    NARCIS (Netherlands)

    Gharib, Sina A.; Loth, Daan W.; Artigas, Maria Soler; Birkland, Timothy P.; Wilk, Jemma B.; Wain, Louise V.; Brody, Jennifer A.; Obeidat, Ma'en; Hancock, Dana B.; Tang, Wenbo; Rawal, Rajesh; Boezen, H. Marike; Imboden, Medea; Huffman, Jennifer E.; Lahousse, Lies; Alves, Alexessander C.; Manichaikul, Ani; Hui, Jennie; Morrison, Alanna C.; Ramasamy, Adaikalavan; Smith, Albert Vernon; Gudnason, Vilmundur; Surakka, Ida; Vitart, Veronique; Evans, David M.; Strachan, David P.; Deary, Ian J.; Hofman, Albert; Glaeser, Sven; Wilson, James F.; North, Kari E.; Zhao, Jing Hua; Heckbert, Susan R.; Jarvis, Deborah L.; Probst-Hensch, Nicole; Schulz, Holger; Barr, R. Graham; Jarvelin, Marjo-Riitta; O'Connor, George T.; Kahonen, Mika; Cassano, Patricia A.; Hysi, Pirro G.; Dupuis, Josee; Hayward, Caroline; Psaty, Bruce M.; Hall, Ian P.; Parks, William C.; Tobin, Martin D.; London, Stephanie J.

    2015-01-01

    Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating p

  13. Integrated translational genomics for analysis of complex traits in sorghum

    Science.gov (United States)

    We will report on the integration of sequencing and genotype data from natural variation (by whole genome resequencing [wgs] or genotype by sequencing [gbs]), transcriptome (RNA-seq) and mutant analysis (also by wgs) with the goal of identifying genes controlling important agronomic traits and tran...

  14. Activity in part of the neural correlates of consciousness reflects integration.

    Science.gov (United States)

    Eriksson, Johan

    2017-07-25

    Integration is commonly viewed as a key process for generating conscious experiences. Accordingly, there should be increased activity within the neural correlates of consciousness when demands on integration increase. We used fMRI and "informational masking" to isolate the neural correlates of consciousness and measured how the associated brain activity changed as a function of required integration. Integration was manipulated by comparing the experience of hearing simple reoccurring tones to hearing harmonic tone triplets. The neural correlates of auditory consciousness included superior temporal gyrus, lateral and medial frontal regions, cerebellum, and also parietal cortex. Critically, only activity in left parietal cortex increased significantly as a function of increasing demands on integration. We conclude that integration can explain part of the neural activity associated with the generation conscious experiences, but that much of associated brain activity apparently reflects other processes. Copyright © 2017. Published by Elsevier Inc.

  15. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

    In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... proposed. This thesis introduced a novel way to integrate such huge data sets in an efficient and informative procedure to dissect the comæexity of obesity related traits (e.g. body wight, body fat, feed intake, etc) and map the flow from DNA through RNA ending with individual phenotypes....

  16. KAIKObase: An integrated silkworm genome database and data mining tool

    Directory of Open Access Journals (Sweden)

    Nagaraju Javaregowda

    2009-10-01

    Full Text Available Abstract Background The silkworm, Bombyx mori, is one of the most economically important insects in many developing countries owing to its large-scale cultivation for silk production. With the development of genomic and biotechnological tools, B. mori has also become an important bioreactor for production of various recombinant proteins of biomedical interest. In 2004, two genome sequencing projects for B. mori were reported independently by Chinese and Japanese teams; however, the datasets were insufficient for building long genomic scaffolds which are essential for unambiguous annotation of the genome. Now, both the datasets have been merged and assembled through a joint collaboration between the two groups. Description Integration of the two data sets of silkworm whole-genome-shotgun sequencing by the Japanese and Chinese groups together with newly obtained fosmid- and BAC-end sequences produced the best continuity (~3.7 Mb in N50 scaffold size among the sequenced insect genomes and provided a high degree of nucleotide coverage (88% of all 28 chromosomes. In addition, a physical map of BAC contigs constructed by fingerprinting BAC clones and a SNP linkage map constructed using BAC-end sequences were available. In parallel, proteomic data from two-dimensional polyacrylamide gel electrophoresis in various tissues and developmental stages were compiled into a silkworm proteome database. Finally, a Bombyx trap database was constructed for documenting insertion positions and expression data of transposon insertion lines. Conclusion For efficient usage of genome information for functional studies, genomic sequences, physical and genetic map information and EST data were compiled into KAIKObase, an integrated silkworm genome database which consists of 4 map viewers, a gene viewer, and sequence, keyword and position search systems to display results and data at the level of nucleotide sequence, gene, scaffold and chromosome. Integration of the

  17. Integrating genomic selection into dairy cattle breeding programmes: a review.

    Science.gov (United States)

    Bouquet, A; Juga, J

    2013-05-01

    Extensive genetic progress has been achieved in dairy cattle populations on many traits of economic importance because of efficient breeding programmes. Success of these programmes has relied on progeny testing of the best young males to accurately assess their genetic merit and hence their potential for breeding. Over the last few years, the integration of dense genomic information into statistical tools used to make selection decisions, commonly referred to as genomic selection, has enabled gains in predicting accuracy of breeding values for young animals without own performance. The possibility to select animals at an early stage allows defining new breeding strategies aimed at boosting genetic progress while reducing costs. The first objective of this article was to review methods used to model and optimize breeding schemes integrating genomic selection and to discuss their relative advantages and limitations. The second objective was to summarize the main results and perspectives on the use of genomic selection in practical breeding schemes, on the basis of the example of dairy cattle populations. Two main designs of breeding programmes integrating genomic selection were studied in dairy cattle. Genomic selection can be used either for pre-selecting males to be progeny tested or for selecting males to be used as active sires in the population. The first option produces moderate genetic gains without changing the structure of breeding programmes. The second option leads to large genetic gains, up to double those of conventional schemes because of a major reduction in the mean generation interval, but it requires greater changes in breeding programme structure. The literature suggests that genomic selection becomes more attractive when it is coupled with embryo transfer technologies to further increase selection intensity on the dam-to-sire pathway. The use of genomic information also offers new opportunities to improve preservation of genetic variation. However

  18. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

    In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...... proposed. This thesis introduced a novel way to integrate such huge data sets in an efficient and informative procedure to dissect the comæexity of obesity related traits (e.g. body wight, body fat, feed intake, etc) and map the flow from DNA through RNA ending with individual phenotypes....

  19. An integrated architecture of adaptive neural network control for dynamic systems

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Liu; Tokar, R.; Mcvey, B.

    1994-07-01

    In this study, an integrated neural network control architecture for nonlinear dynamic systems is presented. Most of the recent emphasis in the neural network control field has no error feedback as the control input which rises the adaptation problem. The integrated architecture in this paper combines feed forward control and error feedback adaptive control using neural networks. The paper reveals the different internal functionality of these two kinds of neural network controllers for certain input styles, e.g., state feedback and error feedback. Feed forward neural network controllers with state feedback establish fixed control mappings which can not adapt when model uncertainties present. With error feedbacks, neural network controllers learn the slopes or the gains respecting to the error feedbacks, which are error driven adaptive control systems. The results demonstrate that the two kinds of control scheme can be combined to realize their individual advantages. Testing with disturbances added to the plant shows good tracking and adaptation.

  20. Integrating genomic resources of flatfish (Pleuronectiformes) to boost aquaculture production.

    Science.gov (United States)

    Robledo, Diego; Hermida, Miguel; Rubiolo, Juan A; Fernández, Carlos; Blanco, Andrés; Bouza, Carmen; Martínez, Paulino

    2017-03-01

    Flatfish have a high market acceptance thus representing a profitable aquaculture production. The main farmed species is the turbot (Scophthalmus maximus) followed by Japanese flounder (Paralichthys olivaceous) and tongue sole (Cynoglossus semilaevis), but other species like Atlantic halibut (Hippoglossus hippoglossus), Senegalese sole (Solea senegalensis) and common sole (Solea solea) also register an important production and are very promising for farming. Important genomic resources are available for most of these species including whole genome sequencing projects, genetic maps and transcriptomes. In this work, we integrate all available genomic information of these species within a common framework, taking as reference the whole assembled genomes of turbot and tongue sole (>210× coverage). New insights related to the genetic basis of productive traits and new data useful to understand the evolutionary origin and diversification of this group were obtained. Despite a general 1:1 chromosome syntenic relationship between species, the comparison of turbot and tongue sole genomes showed huge intrachromosomic reorganizations. The integration of available mapping information supported specific chromosome fusions along flatfish evolution and facilitated the comparison between species of previously reported genetic associations for productive traits. When comparing transcriptomic resources of the six species, a common set of ~2500 othologues and ~150 common miRNAs were identified, and specific sets of putative missing genes were detected in flatfish transcriptomes, likely reflecting their evolutionary diversification. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. DemaDb: an integrated dematiaceous fungal genomes database.

    Science.gov (United States)

    Kuan, Chee Sian; Yew, Su Mei; Chan, Chai Ling; Toh, Yue Fen; Lee, Kok Wei; Cheong, Wei-Hien; Yee, Wai-Yan; Hoh, Chee-Choong; Yap, Soon-Joo; Ng, Kee Peng

    2016-01-01

    Many species of dematiaceous fungi are associated with allergic reactions and potentially fatal diseases in human, especially in tropical climates. Over the past 10 years, we have isolated more than 400 dematiaceous fungi from various clinical samples. In this study, DemaDb, an integrated database was designed to support the integration and analysis of dematiaceous fungal genomes. A total of 92 072 putative genes and 6527 pathways that identified in eight dematiaceous fungi (Bipolaris papendorfii UM 226, Daldinia eschscholtzii UM 1400, D. eschscholtzii UM 1020, Pyrenochaeta unguis-hominis UM 256, Ochroconis mirabilis UM 578, Cladosporium sphaerospermum UM 843, Herpotrichiellaceae sp. UM 238 and Pleosporales sp. UM 1110) were deposited in DemaDb. DemaDb includes functional annotations for all predicted gene models in all genomes, such as Gene Ontology, EuKaryotic Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes (KEGG), Pfam and InterProScan. All predicted protein models were further functionally annotated to Carbohydrate-Active enzymes, peptidases, secondary metabolites and virulence factors. DemaDb Genome Browser enables users to browse and visualize entire genomes with annotation data including gene prediction, structure, orientation and custom feature tracks. The Pathway Browser based on the KEGG pathway database allows users to look into molecular interaction and reaction networks for all KEGG annotated genes. The availability of downloadable files containing assembly, nucleic acid, as well as protein data allows the direct retrieval for further downstream works. DemaDb is a useful resource for fungal research community especially those involved in genome-scale analysis, functional genomics, genetics and disease studies of dematiaceous fungi. Database URL: http://fungaldb.um.edu.my.

  2. An Integrated System for Precise Genome Modification in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Huseyin Tas

    Full Text Available We describe an optimized system for the easy, effective, and precise modification of the Escherichia coli genome. Genome changes are introduced first through the integration of a 1.3 kbp Landing Pad consisting of a gene conferring resistance to tetracycline (tetA or the ability to metabolize the sugar galactose (galK. The Landing Pad is then excised as a result of double-strand breaks by the homing endonuclease I-SceI, and replaced with DNA fragments bearing the desired change via λ-Red mediated homologous recombination. Repair of the double strand breaks and counterselection against the Landing Pad (using NiCl2 for tetA or 2-deoxy-galactose for galK allows the isolation of modified bacteria without the use of additional antibiotic selection. We demonstrate the power of this method to make a variety of genome modifications: the exact integration, without any extraneous sequence, of the lac operon (~6.5 kbp to any desired location in the genome and without the integration of antibiotic markers; the scarless deletion of ribosomal rrn operons (~6 kbp through either intrachromosomal or oligonucleotide recombination; and the in situ fusion of native genes to fluorescent reporter genes without additional perturbation.

  3. Mutation analyses of integrated HBV genome in hepatitis B patients

    Institute of Scientific and Technical Information of China (English)

    Peilin Wang; Xiuhai Wang; Shuying Cong; Hongming Ma; Xuecheng Zhang

    2008-01-01

    Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBF, and in peripheral blood mononuclear cells (PBMC) from 74 cases of HBFs and their children who were born after their fathers' HBV infection (caHBF). We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBF. It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBF. This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

  4. Hybrid neural network fraction integral terminal sliding mode control of an Inchworm robot manipulator

    Science.gov (United States)

    Rahmani, Mehran; Ghanbari, Ahmad; Ettefagh, Mir Mohammad

    2016-12-01

    This paper proposes a control scheme based on the fraction integral terminal sliding mode control and adaptive neural network. It deals with the system model uncertainties and the disturbances to improve the control performance of the Inchworm robot manipulator. A fraction integral terminal sliding mode control applies to the Inchworm robot manipulator to obtain the initial stability. Also, an adaptive neural network is designed to approximate the system uncertainties and unknown disturbances to reduce chattering phenomena. The weight matrix of the proposed adaptive neural network can be updated online, according to the current state error information. The stability of the proposed control method is proved by Lyapunov theory. The performance of the adaptive neural network fraction integral terminal sliding mode control is compared with three other conventional controllers such as sliding mode control, integral terminal sliding mode control and fraction integral terminal sliding mode control. Simulation results show the effectiveness of the proposed control method.

  5. Integrated genomic analysis of breast cancers.

    Science.gov (United States)

    Addou-Klouche, L; Adélaïde, J; Cornen, S; Bekhouche, I; Finetti, P; Guille, A; Sircoulomb, F; Raynaud, S; Bertucci, F; Birnbaum, D; Chaffanet, M

    2012-12-01

    Breast cancer is the most frequent and the most deadly cancer in women in Western countries. Different classifications of disease (anatomoclinical, pathological, prognostic, genetic) are used for guiding the management of patients. Unfortunately, they fail to reflect the whole clinical heterogeneity of the disease. Consequently, molecularly distinct diseases are grouped in similar clinical classes, likely explaining the different clinical outcome between patients in a given class, and the fact that selection of the most appropriate diagnostic or therapeutic strategy for each patient is not done accurately. Today, treatment is efficient in only 70.0-75.0% of cases overall. Our repertoire of efficient drugs is limited but is being expanded with the discovery of new molecular targets for new drugs, based on the identification of candidate oncogenes and tumor suppressor genes (TSG) functionally relevant in disease. Development of new drugs makes therapeutical decisions even more demanding of reliable classifiers and prognostic/predictive tests. Breast cancer is a complex, heterogeneous disease at the molecular level. The combinatorial molecular origin and the heterogeneity of malignant cells, and the variability of the host background, create distinct subgroups of tumors endowed with different phenotypic features such as response to therapy and clinical outcome. Cellular and molecular analyses can identify new classes biologically and clinically relevant, as well as provide new clinically relevant markers and targets. The various stages of mammary tumorigenesis are not clearly defined and the genetic and epigenetic events critical to the development and aggressiveness of breast cancer are not precisely known. Because the phenotype of tumors is dependent on many genes, a large-scale and integrated molecular characterization of the genetic and epigenetic alterations and gene expression deregulation should allow the identification of new molecular classes clinically

  6. Integration of chicken genomic resources to enable whole-genome sequencing

    NARCIS (Netherlands)

    Aerts, J.A.; Crooijmans, R.P.M.A.; Cornelissen, S.J.B.; Hemmatian, K.; Veenendaal, A.; Jaader, A.; Poel, van der J.J.; Fillon, V.; Vignal, I.; Groenen, M.A.M.

    2003-01-01

    Different genomic resources in chicken were integrated through the Wageningen chicken BAC library. First, a BAC anchor map was created by screening this library with two sets of markers: microsatellite markers from the consensus linkage map and markers created from BAC end sequencing in chromosome w

  7. T-DNA Integration Category and Mechanism in Rice Genome

    Institute of Scientific and Technical Information of China (English)

    Jiang WANG; Lin LI; Zhen-Ying SHI; Xin-Shan WAN; Lin-Sheng AN; Jing-Liu ZHANG

    2005-01-01

    T-DNA integration is a key step in the process of plant transformation, which is proven to be important for analyzing T-DNA integration mechanism. The structures of T-DNA right borders inserted into the rice (Oryza sativa L.) genome and their flanking sequences were analyzed. It was found that the integrated ends of the T-DNA right border occurred mainly on five nucleotides "TGACA" in inverse repeat (IR)sequence of 25 bp, especially on the third base "A". However, the integrated ends would sometimes lie inward of the IR sequence, which caused the IR sequence to be lost completely. Sometimes the right integrated ends appeared on the vector sequences rightward of the T-DNA right border, which made the TDNA, carrying vector sequences, integrated into the rice genome. These results seemingly suggest that the IR sequence of the right border plays an important role in the process of T-DNA integration into the rice genome, but is not an essential element. The appearance of vector sequences neighboring the T-DNA right border suggested that before being transferred into the plant cell from Agrobacterium, the entire T-DNA possibly began from the left border in synthesis and then read through at the right border. Several nucleotides in the T-DNA right border homologous with plant DNA and filler DNAs were frequently discovered in the integrated position ofT-DNA. Some small regions in the right border could match with the plant sequence, or form better matches, accompanied by the occurrence of filler DNA, through mutual twisting, and then the TDNA was integrated into plant chromosome through a partially homologous recombination mechanism. The appearance of filler DNA would facilitate T-DNA integration. The fragments flanking the T-DNA right border in transformed rice plants could derive from different parts of the inner T-DNA region; that is, disruption and recombination could occur at arbitrary positions in the entire T-DNA, in which the homologous area was comparatively

  8. Neural correlates of human somatosensory integration in tinnitus

    NARCIS (Netherlands)

    Lanting, C. P.; de Kleine, E.; Eppinga, R. N.; van Dijk, P.

    2010-01-01

    Possible neural correlates of somatosensory modulation of tinnitus were assessed. Functional magnetic resonance imaging (fMRI) was used to investigate differences in neural activity between subjects that can modulate their tinnitus by jaw protrusion and normal hearing controls. We measured responses

  9. Yeast as a touchstone in post-genomic research: strategies for integrative analysis in functional genomics.

    Science.gov (United States)

    Castrillo, Juan I; Oliver, Stephen G

    2004-01-31

    The new complexity arising from the genome sequencing projects requires new comprehensive post-genomic strategies: advanced studies in regulatory mechanisms, application of new high-throughput technologies at a genome-wide scale, at the different levels of cellular complexity (genome, transcriptome, proteome and metabolome), efficient analysis of the results, and application of new bioinformatic methods in an integrative or systems biology perspective. This can be accomplished in studies with model organisms under controlled conditions. In this review a perspective of the favourable characteristics of yeast as a touchstone model in post-genomic research is presented. The state-of-the art, latest advances in the field and bottlenecks, new strategies, new regulatory mechanisms, applications (patents) and high-throughput technologies, most of them being developed and validated in yeast, are presented. The optimal characteristics of yeast as a well-defined system for comprehensive studies under controlled conditions makes it a perfect model to be used in integrative, "systems biology" studies to get new insights into the mechanisms of regulation (regulatory networks) responsible of specific phenotypes under particular environmental conditions, to be applied to more complex organisms (e.g. plants, human).

  10. Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks

    Science.gov (United States)

    Kelley, David R.; Snoek, Jasper; Rinn, John L.

    2016-01-01

    The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance—deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome. PMID:27197224

  11. Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks.

    Science.gov (United States)

    Kelley, David R; Snoek, Jasper; Rinn, John L

    2016-07-01

    The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome.

  12. Lukasiewicz-Topos Models of Neural Networks, Cell Genome and Interactome Nonlinear Dynamic Models

    CERN Document Server

    Baianu, I C

    2004-01-01

    A categorical and Lukasiewicz-Topos framework for Lukasiewicz Algebraic Logic models of nonlinear dynamics in complex functional systems such as neural networks, genomes and cell interactomes is proposed. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous logical models of both genetic activities and neural networks. An algebraic formulation of variable 'next-state functions' is extended to a Lukasiewicz Topos with an n-valued Lukasiewicz Algebraic Logic subobject classifier description that represents non-random and nonlinear network activities as well as their transformations in developmental processes and carcinogenesis.

  13. Hardware implementation of a neural vision system based on a neural network using integrated and fire neurons

    Science.gov (United States)

    González, M.; Lamela, H.; Jiménez, M.; Gimeno, J.; Ruiz-Llata, M.

    2007-04-01

    In this paper we present the scheme for a control circuit used in an image processing system which is to be implemented in a neural network which has a high level of connectivity and reconfiguration of neurons for integration and trigger based on the Address-Event Representation. This scheme will be employed as a pre-processing stage for a vision system which employs as its core processing an Optical Broadcast Neural Network (OBNN). [Optical Engineering letters 42 (9), 2488(2003)]. The proposed vision system allows the possibility to introduce patterns from any acquisition system of images, for posterior processing.

  14. Integrative neural networks models for stream assessment in restoration projects

    Science.gov (United States)

    Gazendam, Ed; Gharabaghi, Bahram; Ackerman, Josef D.; Whiteley, Hugh

    2016-05-01

    Stream-habitat assessment for evaluation of restoration projects requires the examination of many parameters, both watershed-scale and reach-scale, to incorporate the complex non-linear effects of geomorphic, riparian, watershed and hydrologic factors on aquatic ecosystems. Rapid geomorphic assessment tools used by many jurisdictions to assess natural channel design projects seldom include watershed-level parameters, which have been shown to have a significant effect on benthic habitat in stream systems. In this study, Artificial Neural Network (ANN) models were developed to integrate complex non-linear relationships between the aquatic ecosystem health indices and key watershed-scale and reach-scale parameters. Physical stream parameters, based on QHEI parameters, and watershed characteristics data were collected at 112 sites on 62 stream systems located in Southern Ontario. Benthic data were collected separately and benthic invertebrate summary indices, specifically Hilsenhoff's Biotic Index (HBI) and Richness, were determined. The ANN models were trained on the randomly selected 3/4 of the dataset of 112 streams in Ontario, Canada and validated on the remaining 1/4. The R2 values for the developed ANN model predictions were 0.86 for HBI and 0.92 for Richness. Sensitivity analysis of the trained ANN models revealed that Richness was directly proportional to Erosion and Riparian Width and inversely proportional to Floodplain Quality and Substrate parameters. HBI was directly proportional to Velocity Types and Erosion and inversely proportional to Substrate, % Treed and 1:2 Year Flood Flow parameters. The ANN models can be useful tools for watershed managers in stream assessment and restoration projects by allowing consideration of watershed properties in the stream assessment.

  15. Construction of an integrated database to support genomic sequence analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, W.; Overbeek, R.

    1994-11-01

    The central goal of this project is to develop an integrated database to support comparative analysis of genomes including DNA sequence data, protein sequence data, gene expression data and metabolism data. In developing the logic-based system GenoBase, a broader integration of available data was achieved due to assistance from collaborators. Current goals are to easily include new forms of data as they become available and to easily navigate through the ensemble of objects described within the database. This report comments on progress made in these areas.

  16. Integrative activity of neural networks may code virtual spaces with internal representations.

    Science.gov (United States)

    Strelnikov, Kuzma

    2014-10-01

    It was shown recently in neuroimaging that spatial differentiation of brain activity provides novel information about brain function. This confirms the integrative organisation of brain activity, but given present technical limitations of neuroimaging approaches, the exact role of integrative activity remains unclear. We trained a neural network to integrate information using random numbers so as to imitate the "centre-periphery" pattern of brain activity in neuroimaging. Only the hierarchical organisation of the network permitted the learning of fast and reliable integration. We presented images to the trained network and, by spatial differentiation of the network activity, obtained virtual spaces with the presented images. Thus, our study established the necessity of the hierarchical organisation of neural networks for integration and demonstrated that the role of neural integration in the brain may be to create virtual spaces with internal representations of the objects.

  17. Identification of TSS in the Human Genome Based on a RBF Neural Network

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Peng; Jie Chen; Li-Jun Cao; Ting-Ting Gao

    2006-01-01

    The identification of functional motifs in a DNA sequence is fundamentally a statistical pattern recognition problem. This paper introduces a new algorithm for the recognition of functional transcription start sites (TSSs) in human genome sequences, in which a RBF neural network is adopted, and an improved heuristic method for a 5-tuple feature viable construction, is proposed and implemented in two RBFPromoter and ImpRBFPromoter packages developed in Visual C++6.0. The algorithm is evaluated on several different test sequence sets. Compared with several other promoter recognition programs, this algorithm is proved to be more flexible, with stronger learning ability and higher accuracy.

  18. GDR (Genome Database for Rosaceae: integrated web resources for Rosaceae genomics and genetics research

    Directory of Open Access Journals (Sweden)

    Ficklin Stephen

    2004-09-01

    Full Text Available Abstract Background Peach is being developed as a model organism for Rosaceae, an economically important family that includes fruits and ornamental plants such as apple, pear, strawberry, cherry, almond and rose. The genomics and genetics data of peach can play a significant role in the gene discovery and the genetic understanding of related species. The effective utilization of these peach resources, however, requires the development of an integrated and centralized database with associated analysis tools. Description The Genome Database for Rosaceae (GDR is a curated and integrated web-based relational database. GDR contains comprehensive data of the genetically anchored peach physical map, an annotated peach EST database, Rosaceae maps and markers and all publicly available Rosaceae sequences. Annotations of ESTs include contig assembly, putative function, simple sequence repeats, and anchored position to the peach physical map where applicable. Our integrated map viewer provides graphical interface to the genetic, transcriptome and physical mapping information. ESTs, BACs and markers can be queried by various categories and the search result sites are linked to the integrated map viewer or to the WebFPC physical map sites. In addition to browsing and querying the database, users can compare their sequences with the annotated GDR sequences via a dedicated sequence similarity server running either the BLAST or FASTA algorithm. To demonstrate the utility of the integrated and fully annotated database and analysis tools, we describe a case study where we anchored Rosaceae sequences to the peach physical and genetic map by sequence similarity. Conclusions The GDR has been initiated to meet the major deficiency in Rosaceae genomics and genetics research, namely a centralized web database and bioinformatics tools for data storage, analysis and exchange. GDR can be accessed at http://www.genome.clemson.edu/gdr/.

  19. Leader neurons in leaky integrate and fire neural network simulations

    OpenAIRE

    Zbinden, Cyrille

    2010-01-01

    Several experimental studies show the existence of leader neurons in population bursts of 2D living neural networks. A leader neuron is, basically, a neuron which fires at the beginning of a burst (respectively network spike) more often that we expect by looking at its whole mean neural activity. This means that leader neurons have some burst triggering power beyond a simple statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate ...

  20. Genome-wide copy number profiling to detect gene amplifications in neural progenitor cells

    Directory of Open Access Journals (Sweden)

    U. Fischer

    2014-12-01

    Full Text Available DNA sequence amplification occurs at defined stages during normal development in amphibians and flies and seems to be restricted in humans to drug-resistant and tumor cells only. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of human neural progenitor cells. Here, we describe cell culture features, DNA extraction, and comparative genomic hybridization (CGH analysis tailored towards the identification of genomic copy number changes. Further detailed analysis of amplified chromosome regions associated with this experiment, was published by Fischer and colleagues in PLOS One in 2012 (Fischer et al., 2012. We provide detailed information on deleted chromosome regions during differentiation and give an overview on copy number changes during differentiation induction for two representative chromosome regions.

  1. A hybrid neural network system for prediction and recognition of promoter regions in human genome

    Institute of Scientific and Technical Information of China (English)

    CHEN Chuan-bo; LI Tao

    2005-01-01

    This paper proposes a high specificity and sensitivity algorithm called PromPredictor for recognizing promoter regions in the human genome. PromPredictor extracts compositional features and CpG islands information from genomic sequence,feeding these features as input for a hybrid neural network system (HNN) and then applies the HNN for prediction. It combines a novel promoter recognition model, coding theory, feature selection and dimensionality reduction with machine learning algorithm.Evaluation on Human chromosome 22 was ~66% in sensitivity and ~48% in specificity. Comparison with two other systems revealed that our method had superior sensitivity and specificity in predicting promoter regions. PromPredictor is written in MATLAB and requires Matlab to run. PromPredictor is freely available at http://www.whtelecom.com/Prompredictor.htm.

  2. Ultrasoft microwire neural electrodes improve chronic tissue integration.

    Science.gov (United States)

    Du, Zhanhong Jeff; Kolarcik, Christi L; Kozai, Takashi D Y; Luebben, Silvia D; Sapp, Shawn A; Zheng, Xin Sally; Nabity, James A; Cui, X Tracy

    2017-02-06

    Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants.

  3. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Andrei L. Osterman, Ph.D.

    2012-12-17

    Integration of bioinformatics and experimental techniques was applied to mapping and characterization of the key components (pathways, enzymes, transporters, regulators) of the core metabolic machinery in Shewanella oneidensis and related species with main focus was on metabolic and regulatory pathways involved in utilization of various carbon and energy sources. Among the main accomplishments reflected in ten joint publications with other participants of Shewanella Federation are: (i) A systems-level reconstruction of carbohydrate utilization pathways in the genus of Shewanella (19 species). This analysis yielded reconstruction of 18 sugar utilization pathways including 10 novel pathway variants and prediction of > 60 novel protein families of enzymes, transporters and regulators involved in these pathways. Selected functional predictions were verified by focused biochemical and genetic experiments. Observed growth phenotypes were consistent with bioinformatic predictions providing strong validation of the technology and (ii) Global genomic reconstruction of transcriptional regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors, 8 riboswitches and 6 translational attenuators. Of those, 45 regulons were inferred directly from the genome context analysis, whereas others were propagated from previously characterized regulons in other species. Selected regulatory predictions were experimentally tested. Integration of this analysis with microarray data revealed overall consistency and provided additional layer of interactions between regulons. All the results were captured in the new database RegPrecise, which is a joint development with the LBNL team. A more detailed analysis of the individual subsystems, pathways and regulons in Shewanella spp included bioinfiormatics-based prediction and experimental characterization of: (i) N-Acetylglucosamine catabolic pathway; (ii)Lactate utilization machinery; (iii) Novel Nrt

  4. [Building artificial neural networks model on portable NIR integrity wheat component measuring apparatus].

    Science.gov (United States)

    Ji, Hai-yan; Wen, Ming; Hao, Bin

    2006-01-01

    The quantitative analysis model of protein in integrity wheat was built by three layers back propagation artificial neural networks for portable near infrared (NIR) integrity wheat component measuring apparatus. The structure diagram of integrity wheat component measuring apparatus, light route structure of apparatus and the spectrum of integrity wheat were given in the present paper. The theory of artificial neural network was briefly introduced and the results of quantitative analysis model of protein were given. For calibration set and prediction set, the correlation coefficient was 0.90 and 0.96 respectively; the relative standard deviation is 3.77% and 4.46% respectively. Because of the influence of light route structure, electrical circuit, and integrity sample forms on the measuring apparatus, some nonlinearity exists between the spectral parameters and chemical values. The results of artificial neural networks nonlinear model were superior to linear model.

  5. Is integration and survival of newborn neurons the bottleneck for effective neural repair by endogenous neural precursor cells?

    Directory of Open Access Journals (Sweden)

    Ann eTurnley

    2014-02-01

    Full Text Available After two decades of research the existence of adult neural precursor cells and the phenomenon of adult neurogenesis is well established. However, there has been little or no effective harnessing of these endogenous cells to promote functional neuronal replacement following neural injury or disease. Neural precursor cells can respond to neural damage by proliferating, migrating to the site of injury and differentiating into neuronal or glial lineages. However, after a month or so, very few or no newborn neurons can be detected, suggesting that even though neuroblasts are generated, they generally fail to survive as mature neurons and contribute to the local circuitry. Is this lack of survival and integration one of the major bottlenecks that inhibits effective neuronal replacement and subsequent repair of the nervous system following injury or disease? In this perspective article the possibility that this bottleneck can be targeted to enhance the integration and subsequent survival of newborn neurons will be explored and will suggest some possible mechanisms that may need to be modulated for this to occur.

  6. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis.

    Science.gov (United States)

    Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M; Li, Yang; Brown, Eric J; Russell, Helen R; McKinnon, Peter J

    2017-01-25

    The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G2/M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system.

  7. An integrated semiconductor device enabling non-optical genome sequencing.

    Science.gov (United States)

    Rothberg, Jonathan M; Hinz, Wolfgang; Rearick, Todd M; Schultz, Jonathan; Mileski, William; Davey, Mel; Leamon, John H; Johnson, Kim; Milgrew, Mark J; Edwards, Matthew; Hoon, Jeremy; Simons, Jan F; Marran, David; Myers, Jason W; Davidson, John F; Branting, Annika; Nobile, John R; Puc, Bernard P; Light, David; Clark, Travis A; Huber, Martin; Branciforte, Jeffrey T; Stoner, Isaac B; Cawley, Simon E; Lyons, Michael; Fu, Yutao; Homer, Nils; Sedova, Marina; Miao, Xin; Reed, Brian; Sabina, Jeffrey; Feierstein, Erika; Schorn, Michelle; Alanjary, Mohammad; Dimalanta, Eileen; Dressman, Devin; Kasinskas, Rachel; Sokolsky, Tanya; Fidanza, Jacqueline A; Namsaraev, Eugeni; McKernan, Kevin J; Williams, Alan; Roth, G Thomas; Bustillo, James

    2011-07-20

    The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.

  8. Genomic DNA hypomethylation is associated with neural tube defects induced by methotrexate inhibition of folate metabolism.

    Directory of Open Access Journals (Sweden)

    Xiuwei Wang

    Full Text Available DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs. However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS, liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS, microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005, 5-formyltetrahydrofolate (5-FoTHF, P = 0.040, S-adenosylmethionine (SAM, P = 0.004 and higher concentrations of folic acid (P = 0.041, homocysteine (Hcy, P = 0.006 and S-adenosylhomocysteine (SAH, P = 0.045 compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions were selected by microarray. Two genes (Siah1b, Prkx in Wnt signal pathway demonstrated lower methylated regions (peak and higher expression in NTDs (P<0.05; P<0.05. Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs.

  9. Genomic DNA hypomethylation is associated with neural tube defects induced by methotrexate inhibition of folate metabolism.

    Science.gov (United States)

    Wang, Xiuwei; Guan, Zhen; Chen, Yan; Dong, Yanting; Niu, Yuhu; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-01-01

    DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs). However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS), liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS), microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005), 5-formyltetrahydrofolate (5-FoTHF, P = 0.040), S-adenosylmethionine (SAM, P = 0.004) and higher concentrations of folic acid (P = 0.041), homocysteine (Hcy, P = 0.006) and S-adenosylhomocysteine (SAH, P = 0.045) compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions) were selected by microarray. Two genes (Siah1b, Prkx) in Wnt signal pathway demonstrated lower methylated regions (peak) and higher expression in NTDs (P<0.05; P<0.05). Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs.

  10. Varying Timescales of Stimulus Integration Unite Neural Adaptation and Prototype Formation.

    Science.gov (United States)

    Mattar, Marcelo G; Kahn, David A; Thompson-Schill, Sharon L; Aguirre, Geoffrey K

    2016-07-11

    Human visual perception is both stable and adaptive. Perception of complex objects, such as faces, is shaped by the long-term average of experience as well as immediate, comparative context. Measurements of brain activity have demonstrated corresponding neural mechanisms, including norm-based responses reflective of stored prototype representations, and adaptation induced by the immediately preceding stimulus. Here, we consider the possibility that these apparently separate phenomena can arise from a single mechanism of sensory integration operating over varying timescales. We used fMRI to measure neural responses from the fusiform gyrus while subjects observed a rapid stream of face stimuli. Neural activity at this cortical site was best explained by the integration of sensory experience over multiple sequential stimuli, following a decaying-exponential weighting function. Although this neural activity could be mistaken for immediate neural adaptation or long-term, norm-based responses, it in fact reflected a timescale of integration intermediate to both. We then examined the timescale of sensory integration across the cortex. We found a gradient that ranged from rapid sensory integration in early visual areas, to long-term, stable representations in higher-level, ventral-temporal cortex. These findings were replicated with a new set of face stimuli and subjects. Our results suggest that a cascade of visual areas integrate sensory experience, transforming highly adaptable responses at early stages to stable representations at higher levels.

  11. Neural networks for structural design - An integrated system implementation

    Science.gov (United States)

    Berke, Laszlo; Hafez, Wassim; Pao, Yoh-Han

    1992-01-01

    The development of powerful automated procedures to aid the creative designer is becoming increasingly critical for complex design tasks. In the work described here Artificial Neural Nets are applied to acquire structural analysis and optimization domain expertise. Based on initial instructions from the user an automated procedure generates random instances of structural analysis and/or optimization 'experiences' that cover a desired domain. It extracts training patterns from the created instances, constructs and trains an appropriate network architecture and checks the accuracy of net predictions. The final product is a trained neural net that can estimate analysis and/or optimization results instantaneously.

  12. INTEGRATING ARTIFICIAL NEURAL NETWORKS FOR DEVELOPING TELEMEDICINE SOLUTION

    Directory of Open Access Journals (Sweden)

    Mihaela GHEORGHE

    2015-06-01

    Full Text Available Artificial intelligence is assuming an increasing important role in the telemedicine field, especially neural networks with their ability to achieve meaning from large sets of data characterized by lacking exactness and accuracy. These can be used for assisting physicians or other clinical staff in the process of taking decisions under uncertainty. Thus, machine learning methods which are specific to this technology are offering an approach for prediction based on pattern classification. This paper aims to present the importance of neural networks in detecting trends and extracting patterns which can be used within telemedicine domains, particularly for taking medical diagnosis decisions.

  13. An integrative computational approach for prioritization of genomic variants.

    Directory of Open Access Journals (Sweden)

    Inna Dubchak

    Full Text Available An essential step in the discovery of molecular mechanisms contributing to disease phenotypes and efficient experimental planning is the development of weighted hypotheses that estimate the functional effects of sequence variants discovered by high-throughput genomics. With the increasing specialization of the bioinformatics resources, creating analytical workflows that seamlessly integrate data and bioinformatics tools developed by multiple groups becomes inevitable. Here we present a case study of a use of the distributed analytical environment integrating four complementary specialized resources, namely the Lynx platform, VISTA RViewer, the Developmental Brain Disorders Database (DBDB, and the RaptorX server, for the identification of high-confidence candidate genes contributing to pathogenesis of spina bifida. The analysis resulted in prediction and validation of deleterious mutations in the SLC19A placental transporter in mothers of the affected children that causes narrowing of the outlet channel and therefore leads to the reduced folate permeation rate. The described approach also enabled correct identification of several genes, previously shown to contribute to pathogenesis of spina bifida, and suggestion of additional genes for experimental validations. The study demonstrates that the seamless integration of bioinformatics resources enables fast and efficient prioritization and characterization of genomic factors and molecular networks contributing to the phenotypes of interest.

  14. An Integrative Computational Approach for Prioritization of Genomic Variants

    Science.gov (United States)

    Wang, Sheng; Meyden, Cem; Sulakhe, Dinanath; Poliakov, Alexander; Börnigen, Daniela; Xie, Bingqing; Taylor, Andrew; Ma, Jianzhu; Paciorkowski, Alex R.; Mirzaa, Ghayda M.; Dave, Paul; Agam, Gady; Xu, Jinbo; Al-Gazali, Lihadh; Mason, Christopher E.; Ross, M. Elizabeth; Maltsev, Natalia; Gilliam, T. Conrad

    2014-01-01

    An essential step in the discovery of molecular mechanisms contributing to disease phenotypes and efficient experimental planning is the development of weighted hypotheses that estimate the functional effects of sequence variants discovered by high-throughput genomics. With the increasing specialization of the bioinformatics resources, creating analytical workflows that seamlessly integrate data and bioinformatics tools developed by multiple groups becomes inevitable. Here we present a case study of a use of the distributed analytical environment integrating four complementary specialized resources, namely the Lynx platform, VISTA RViewer, the Developmental Brain Disorders Database (DBDB), and the RaptorX server, for the identification of high-confidence candidate genes contributing to pathogenesis of spina bifida. The analysis resulted in prediction and validation of deleterious mutations in the SLC19A placental transporter in mothers of the affected children that causes narrowing of the outlet channel and therefore leads to the reduced folate permeation rate. The described approach also enabled correct identification of several genes, previously shown to contribute to pathogenesis of spina bifida, and suggestion of additional genes for experimental validations. The study demonstrates that the seamless integration of bioinformatics resources enables fast and efficient prioritization and characterization of genomic factors and molecular networks contributing to the phenotypes of interest. PMID:25506935

  15. Integrative Genomics with Mediation Analysis in a Survival Context

    Directory of Open Access Journals (Sweden)

    Szilárd Nemes

    2013-01-01

    Full Text Available DNA copy number aberrations (DCNA and subsequent altered gene expression profiles may have a major impact on tumor initiation, on development, and eventually on recurrence and cancer-specific mortality. However, most methods employed in integrative genomic analysis of the two biological levels, DNA and RNA, do not consider survival time. In the present note, we propose the adoption of a survival analysis-based framework for the integrative analysis of DCNA and mRNA levels to reveal their implication on patient clinical outcome with the prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA-survival pathway. We provide statistical inference algorithms for mediation based on asymptotic results. Furthermore, we illustrate the applicability of the method in an integrative genomic analysis setting by using a breast cancer data set consisting of 141 invasive breast tumors. In addition, we provide implementation in R.

  16. Integrated Genome-Based Studies of Shewanella Echophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Margrethe H. Serres

    2012-06-29

    Shewanella oneidensis MR-1 is a motile, facultative {gamma}-Proteobacterium with remarkable respiratory versatility; it can utilize a range of organic and inorganic compounds as terminal electronacceptors for anaerobic metabolism. The ability to effectively reduce nitrate, S0, polyvalent metals andradionuclides has established MR-1 as an important model dissimilatory metal-reducing microorganism for genome-based investigations of biogeochemical transformation of metals and radionuclides that are of concern to the U.S. Department of Energy (DOE) sites nationwide. Metal-reducing bacteria such as Shewanella also have a highly developed capacity for extracellular transfer of respiratory electrons to solid phase Fe and Mn oxides as well as directly to anode surfaces in microbial fuel cells. More broadly, Shewanellae are recognized free-living microorganisms and members of microbial communities involved in the decomposition of organic matter and the cycling of elements in aquatic and sedimentary systems. To function and compete in environments that are subject to spatial and temporal environmental change, Shewanella must be able to sense and respond to such changes and therefore require relatively robust sensing and regulation systems. The overall goal of this project is to apply the tools of genomics, leveraging the availability of genome sequence for 18 additional strains of Shewanella, to better understand the ecophysiology and speciation of respiratory-versatile members of this important genus. To understand these systems we propose to use genome-based approaches to investigate Shewanella as a system of integrated networks; first describing key cellular subsystems - those involved in signal transduction, regulation, and metabolism - then building towards understanding the function of whole cells and, eventually, cells within populations. As a general approach, this project will employ complimentary "top-down" - bioinformatics-based genome functional predictions, high

  17. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.

    Directory of Open Access Journals (Sweden)

    Yuichi Shiraishi

    Full Text Available Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs and their matched controls. Comparison of whole genome sequence (WGS and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3, and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.

  18. QUADRATIC PROGRAMMING NEURAL NETWORK BASED INTEGRATED SPACE-TIME INTERFERENCE SUPPRESSION IN CDMA SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Song Rongfang; Bi Guangguo

    2001-01-01

    Quadratic programming models for integrated space-time interference suppression in CDMA systems are proposed in this paper. The models integrate the advantages of smart antenna and RAKE receiver, mitigate multiuser access interference (MAI) and interchip interference (ICI),and combine multipath components. The zero-forcing conditions are derived. Neural network implementation of the models is also studied.

  19. Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration.

    Science.gov (United States)

    Kuo, Jonathan T W; Kim, Brian J; Hara, Seth A; Lee, Curtis D; Gutierrez, Christian A; Hoang, Tuan Q; Meng, Ellis

    2013-02-21

    A Parylene C neural probe with a three dimensional sheath structure was designed, fabricated, and characterized. Multiple platinum (Pt) electrodes for recording neural signals were fabricated on both inner and outer surfaces of the sheath structure. Thermoforming of Parylene was used to create the three dimensional sheath structures from flat surface micromachined microchannels using solid microwires as molds. Benchtop electrochemical characterization was performed on the thin film Pt electrodes using cyclic voltammetry and electrochemical impedance spectroscopy and showed that electrodes possessed low impedances suitable for neuronal recordings. A procedure for implantation of the neural probe was developed and successfully demonstrated in vitro into an agarose brain tissue model. The electrode-lined sheath will be decorated with eluting neurotrophic factors to promote in vivo neural tissue ingrowth post-implantation. These features will enhance tissue integration and improve recording quality towards realizing reliable chronic neural interfaces.

  20. A Study on Integrated Wavelet Neural Networks in Fault Diagnosis Based on Information Fusion

    Institute of Scientific and Technical Information of China (English)

    ANG Xue-ye

    2007-01-01

    The tight wavelet neural network was constituted by taking the nonlinear Morlet wavelet radices as the excitation function. The idiographic algorithm was presented. It combined the advantages of wavelet analysis and neural networks. The integrated wavelet neural network fault diagnosis system was set up based on both the information fusion technology and actual fault diagnosis, which took the sub-wavelet neural network as primary diagnosis from different sides, then came to the conclusions through decision-making fusion. The realizable policy of the diagnosis system and established principle of the sub-wavelet neural networks were given . It can be deduced from the examples that it takes full advantage of diversified characteristic information, and improves the diagnosis rate.

  1. Genomic factors that shape craniofacial outcome and neural crest vulnerability in FASD

    Directory of Open Access Journals (Sweden)

    Susan M. Smith

    2014-08-01

    Full Text Available Prenatal alcohol exposure (PAE causes distinctive facial characteristics in some pregnancies and not others; genetic factors may contribute to this differential vulnerability. Ethanol disrupts multiple events of neural crest development including induction, survival, migration, and differentiation. Animal models and genomic approaches have substantially advanced our understanding of the mechanisms underlying these facial changes. PAE during gastrulation produces craniofacial changes corresponding with human fetal alcohol syndrome. These result because PAE reduces prechordal plate extension and suppresses sonic hedgehog, leading to holoprosencephaly and malpositioned facial primordia. Haploinsufficiency in sonic hedgehog signaling increases vulnerability to facial deficits and may influence some PAE pregnancies. In contrast, PAE during early neurogenesis produces facial hypoplasia, preceded by neural crest reductions due to significant apoptosis. Factors mediating this apoptosis include intracellular calcium mobilization, elevated reactive oxygen species, and loss of trophic support from β-catenin/calcium, sonic hedgehog, and mTOR signaling. Genomewide SNP analysis links PDGF receptor genes with facial outcomes in human PAE. Multiple genomic-level comparisons of ethanol-sensitive and –resistant early embryos, in both mouse and chick, independently identify common candidate genes that may potentially modify craniofacial vulnerability, including ribosomal proteins, proteosome, RNA splicing, and focal adhesion. In summary, research using animal models with genome-level differences in ethanol vulnerability, as well as targeted loss- and gain-of-function mutants, has clarified the mechanisms mediating craniofacial change in PAE. The findings additionally suggest that craniofacial deficits may represent a gene-ethanol interaction for some affected individuals. Genetic-level changes may prime individuals toward greater sensitivity or resistance to

  2. Artificial Neural Network Based State Estimators Integrated into Kalmtool

    DEFF Research Database (Denmark)

    Bayramoglu, Enis; Ravn, Ole; Poulsen, Niels Kjølstad

    2012-01-01

    In this paper we present a toolbox enabling easy evaluation and comparison of dierent ltering algorithms. The toolbox is called Kalmtool and is a set of MATLAB tools for state estimation of nonlinear systems. The toolbox now contains functions for Articial Neural Network Based State Estimation...

  3. Forecasting SPEI and SPI Drought Indices Using the Integrated Artificial Neural Networks.

    Science.gov (United States)

    Maca, Petr; Pech, Pavel

    2016-01-01

    The presented paper compares forecast of drought indices based on two different models of artificial neural networks. The first model is based on feedforward multilayer perceptron, sANN, and the second one is the integrated neural network model, hANN. The analyzed drought indices are the standardized precipitation index (SPI) and the standardized precipitation evaporation index (SPEI) and were derived for the period of 1948-2002 on two US catchments. The meteorological and hydrological data were obtained from MOPEX experiment. The training of both neural network models was made by the adaptive version of differential evolution, JADE. The comparison of models was based on six model performance measures. The results of drought indices forecast, explained by the values of four model performance indices, show that the integrated neural network model was superior to the feedforward multilayer perceptron with one hidden layer of neurons.

  4. Forecasting SPEI and SPI Drought Indices Using the Integrated Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Petr Maca

    2016-01-01

    Full Text Available The presented paper compares forecast of drought indices based on two different models of artificial neural networks. The first model is based on feedforward multilayer perceptron, sANN, and the second one is the integrated neural network model, hANN. The analyzed drought indices are the standardized precipitation index (SPI and the standardized precipitation evaporation index (SPEI and were derived for the period of 1948–2002 on two US catchments. The meteorological and hydrological data were obtained from MOPEX experiment. The training of both neural network models was made by the adaptive version of differential evolution, JADE. The comparison of models was based on six model performance measures. The results of drought indices forecast, explained by the values of four model performance indices, show that the integrated neural network model was superior to the feedforward multilayer perceptron with one hidden layer of neurons.

  5. Ionic mechanisms subserving mechanosensory transduction and neural integration in statocyst hair cells of Hermissenda

    Science.gov (United States)

    Farley, Joseph

    1988-01-01

    The neural processing of gravitational-produced sensory stimulation of statocyst hair cells in the nudibranch mollusk Hermissenda was studied. The goal in these studies was to understand how: gravireceptor neurons sense or transduce gravitational forces, gravitational stimulation is integrated so as to produce a graded receptor potential, and ultimately the generation of an action potential, and various neural adaptation phenomena which hair cells exhibit arise. The approach to these problems was primarily electrophysical.

  6. Optimal multiple-information integration inherent in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-02-01

    Although several behavioral experiments have suggested that our neural system integrates multiple sources of information based on the certainty of each type of information in the manner of maximum-likelihood estimation, it is unclear how the maximum-likelihood estimation is implemented in our neural system. Here, I investigate the relationship between maximum-likelihood estimation and a widely used ring-type neural network model that is used as a model of visual, motor, or prefrontal cortices. Without any approximation or ansatz, I analytically demonstrate that the equilibrium of an order parameter in the neural network model exactly corresponds to the maximum-likelihood estimation when the strength of the symmetrical recurrent synaptic connectivity within a neural population is appropriately stronger than that of asymmetrical connectivity, that of local and external inputs, and that of symmetrical or asymmetrical connectivity between different neural populations. In this case, strengths of local and external inputs or those of symmetrical connectivity between different neural populations exactly correspond to the input certainty in maximum-likelihood estimation. Thus, my analysis suggests appropriately strong symmetrical recurrent connectivity as a possible candidate for implementing the maximum-likelihood estimation within our neural system.

  7. Integrative genome-wide approaches in embryonic stem cell research.

    Science.gov (United States)

    Zhang, Xinyue; Huang, Jing

    2010-10-01

    Embryonic stem (ES) cells are derived from blastocysts. They can differentiate into the three embryonic germ layers and essentially any type of somatic cells. They therefore hold great potential in tissue regeneration therapy. The ethical issues associated with the use of human embryonic stem cells are resolved by the technical break-through of generating induced pluripotent stem (iPS) cells from various types of somatic cells. However, how ES and iPS cells self-renew and maintain their pluripotency is still largely unknown in spite of the great progress that has been made in the last two decades. Integrative genome-wide approaches, such as the gene expression microarray, chromatin immunoprecipitation based microarray (ChIP-chip) and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) offer unprecedented opportunities to elucidate the mechanism of the pluripotency, reprogramming and DNA damage response of ES and iPS cells. This frontier article summarizes the fundamental biological questions about ES and iPS cells and reviews the recent advances in ES and iPS cell research using genome-wide technologies. To this end, we offer our perspectives on the future of genome-wide studies on stem cells.

  8. An integrated genetic and cytogenetic map of the cucumber genome.

    Directory of Open Access Journals (Sweden)

    Yi Ren

    Full Text Available The Cucurbitaceae includes important crops such as cucumber, melon, watermelon, squash and pumpkin. However, few genetic and genomic resources are available for plant improvement. Some cucurbit species such as cucumber have a narrow genetic base, which impedes construction of saturated molecular linkage maps. We report herein the development of highly polymorphic simple sequence repeat (SSR markers originated from whole genome shotgun sequencing and the subsequent construction of a high-density genetic linkage map. This map includes 995 SSRs in seven linkage groups which spans in total 573 cM, and defines approximately 680 recombination breakpoints with an average of 0.58 cM between two markers. These linkage groups were then assigned to seven corresponding chromosomes using fluorescent in situ hybridization (FISH. FISH assays also revealed a chromosomal inversion between Cucumis subspecies [C. sativus var. sativus L. and var. hardwickii (R. Alef], which resulted in marker clustering on the genetic map. A quarter of the mapped markers showed relatively high polymorphism levels among 11 inbred lines of cucumber. Among the 995 markers, 49%, 26% and 22% were conserved in melon, watermelon and pumpkin, respectively. This map will facilitate whole genome sequencing, positional cloning, and molecular breeding in cucumber, and enable the integration of knowledge of gene and trait in cucurbits.

  9. The Proteins API: accessing key integrated protein and genome information.

    Science.gov (United States)

    Nightingale, Andrew; Antunes, Ricardo; Alpi, Emanuele; Bursteinas, Borisas; Gonzales, Leonardo; Liu, Wudong; Luo, Jie; Qi, Guoying; Turner, Edd; Martin, Maria

    2017-04-05

    The Proteins API provides searching and programmatic access to protein and associated genomics data such as curated protein sequence positional annotations from UniProtKB, as well as mapped variation and proteomics data from large scale data sources (LSS). Using the coordinates service, researchers are able to retrieve the genomic sequence coordinates for proteins in UniProtKB. This, the LSS genomics and proteomics data for UniProt proteins is programmatically only available through this service. A Swagger UI has been implemented to provide documentation, an interface for users, with little or no programming experience, to 'talk' to the services to quickly and easily formulate queries with the services and obtain dynamically generated source code for popular programming languages, such as Java, Perl, Python and Ruby. Search results are returned as standard JSON, XML or GFF data objects. The Proteins API is a scalable, reliable, fast, easy to use RESTful services that provides a broad protein information resource for users to ask questions based upon their field of expertise and allowing them to gain an integrated overview of protein annotations available to aid their knowledge gain on proteins in biological processes. The Proteins API is available at (http://www.ebi.ac.uk/proteins/api/doc).

  10. Improving GPS/INS Integration through Neural Networks

    CERN Document Server

    Nguyen-H, M

    2010-01-01

    The Global Positioning Systems (GPS) and Inertial Navigation System (INS) technology have attracted a considerable importance recently because of its large number of solutions serving both military as well as civilian applications. This paper aims to develop a more efficient and especially a faster method for processing the GPS signal in case of INS signal loss without losing the accuracy of the data. The conventional or usual method consists of processing data through a neural network and obtaining accurate positioning output data. The new or improved method adds selective filtering at the low-band frequency, the mid-band frequency and the high band frquency, before processing the GPS data through the neural network, so that the processing time is decreased significantly while the accuracy remains the same.

  11. Integration of Neural Networks and Cellular Automata for Urban Planning

    Institute of Scientific and Technical Information of China (English)

    Anthony Gar-on Yeh; LI Xia

    2004-01-01

    This paper presents a new type of cellular automata (CA) model for the simulation of alternative land development using neural networks for urban planning. CA models can be regarded as a planning tool because they can generate alternative urban growth. Alternative development patterns can be formed by using different sets of parameter values in CA simulation. A critical issue is how to define parameter values for realistic and idealized simulation. This paper demonstrates that neural networks can simplify CA models but generate more plausible results. The simulation is based on a simple three-layer network with an output neuron to generate conversion probability. No transition rules are required for the simulation. Parameter values are automatically obtained from the training of network by using satellite remote sensing data. Original training data can be assessed and modified according to planning objectives. Alternative urban patterns can be easily formulated by using the modified training data sets rather than changing the model.

  12. Design of Experimentation, Artificial Neural Network Simulation and Optimization for Integrated Bamboo Processing Machine

    OpenAIRE

    P. G. Mehar; Dr.A.V.Vanalkar

    2015-01-01

    In this research work experimentation on integrated bamboo processing machine for splitting and slicing of bamboo has been carried out. This paper presents the experimental investigation of some parameters of integrated bamboo processing machine. In this research paper simulation of experimental data using artificial neural network is carried out. An attempt of minimum-maximum principle has been made to optimize by range bound process for maximizing production rate of integrated b...

  13. Design of Experimentation, Artificial Neural Network Simulation and Optimization for Integrated Bamboo Processing Machine

    Directory of Open Access Journals (Sweden)

    P. G. Mehar

    2015-11-01

    Full Text Available In this research work experimentation on integrated bamboo processing machine for splitting and slicing of bamboo has been carried out. This paper presents the experimental investigation of some parameters of integrated bamboo processing machine. In this research paper simulation of experimental data using artificial neural network is carried out. An attempt of minimum-maximum principle has been made to optimize by range bound process for maximizing production rate of integrated bamboo processing machine.

  14. INDIGO - INtegrated data warehouse of microbial genomes with examples from the red sea extremophiles.

    KAUST Repository

    Alam, Intikhab

    2013-12-06

    The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes.

  15. An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization.

    Science.gov (United States)

    Szałaj, Przemysław; Tang, Zhonghui; Michalski, Paul; Pietal, Michal J; Luo, Oscar J; Sadowski, Michał; Li, Xingwang; Radew, Kamen; Ruan, Yijun; Plewczynski, Dariusz

    2016-12-01

    ChIA-PET is a high-throughput mapping technology that reveals long-range chromatin interactions and provides insights into the basic principles of spatial genome organization and gene regulation mediated by specific protein factors. Recently, we showed that a single ChIA-PET experiment provides information at all genomic scales of interest, from the high-resolution locations of binding sites and enriched chromatin interactions mediated by specific protein factors, to the low resolution of nonenriched interactions that reflect topological neighborhoods of higher-order chromosome folding. This multilevel nature of ChIA-PET data offers an opportunity to use multiscale 3D models to study structural-functional relationships at multiple length scales, but doing so requires a structural modeling platform. Here, we report the development of 3D-GNOME (3-Dimensional Genome Modeling Engine), a complete computational pipeline for 3D simulation using ChIA-PET data. 3D-GNOME consists of three integrated components: a graph-distance-based heat map normalization tool, a 3D modeling platform, and an interactive 3D visualization tool. Using ChIA-PET and Hi-C data derived from human B-lymphocytes, we demonstrate the effectiveness of 3D-GNOME in building 3D genome models at multiple levels, including the entire genome, individual chromosomes, and specific segments at megabase (Mb) and kilobase (kb) resolutions of single average and ensemble structures. Further incorporation of CTCF-motif orientation and high-resolution looping patterns in 3D simulation provided additional reliability of potential biologically plausible topological structures.

  16. The octopus genome and the evolution of cephalopod neural and morphological novelties

    Science.gov (United States)

    Albertin, Caroline B.; Simakov, Oleg; Mitros, Therese; Wang, Z. Yan; Pungor, Judit R.; Edsinger-Gonzalez, Eric; Brenner, Sydney; Ragsdale, Clifton W.; Rokhsar, Daniel S.

    2016-01-01

    Coleoid cephalopods (octopus, squid, and cuttlefish) are active, resourceful predators with a rich behavioral repertoire1. They have the largest nervous systems among the invertebrates2 and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis, and the most sophisticated adaptive coloration system among all animals1,3. To investigate the molecular bases of cephalopod brain and body innovations we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole genome duplications in the octopus lineage4–6. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families formerly thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc finger transcription factors. Extensive mRNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described7, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers, and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodeling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems. PMID:26268193

  17. The octopus genome and the evolution of cephalopod neural and morphological novelties.

    Science.gov (United States)

    Albertin, Caroline B; Simakov, Oleg; Mitros, Therese; Wang, Z Yan; Pungor, Judit R; Edsinger-Gonzales, Eric; Brenner, Sydney; Ragsdale, Clifton W; Rokhsar, Daniel S

    2015-08-13

    Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire. They have the largest nervous systems among the invertebrates and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis and a remarkably sophisticated adaptive colouration system. To investigate the molecular bases of cephalopod brain and body innovations, we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole-genome duplications in the octopus lineage. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families previously thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc-finger transcription factors. Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.

  18. The integrated microbial genomes (IMG) system in 2007: datacontent and analysis tool extensions

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, Victor M.; Szeto, Ernest; Palaniappan, Krishna; Grechkin, Yuri; Chu, Ken; Chen, I-Min A.; Dubchak, Inna; Anderson, Iain; Lykidis, Athanasios; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2007-08-01

    The Integrated Microbial Genomes (IMG) system is a data management, analysis and annotation platform for all publicly available genomes. IMG contains both draft and complete JGI microbial genomes integrated with all other publicly available genomes from all three domains of life, together with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and annotating genomes, genes and functions, individually or in a comparative context. Since its first release in 2005, IMG's data content and analytical capabilities have been constantly expanded through quarterly releases. IMG is provided by the DOE-Joint Genome Institute (JGI) and is available from http://img.jgi.doe.gov.

  19. Integrated cytogenetics and genomics analysis of transposable elements in the Nile tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Valente, Guilherme; Kocher, Thomas; Eickbush, Thomas; Simões, Rafael P; Martins, Cesar

    2016-06-01

    Integration of cytogenetics and genomics has become essential to a better view of architecture and function of genomes. Although the advances on genomic sequencing have contributed to study genes and genomes, the repetitive DNA fraction of the genome is still enigmatic and poorly understood. Among repeated DNAs, transposable elements (TEs) are major components of eukaryotic chromatin and their investigation has been hindered even after the availability of whole sequenced genomes. The cytogenetic mapping of TEs in chromosomes has proved to be of high value to integrate information from the micro level of nucleotide sequence to a cytological view of chromosomes. Different TEs have been cytogenetically mapped in cichlids; however, neither details about their genomic arrangement nor appropriated copy number are well defined by these approaches. The current study integrates TEs distribution in Nile tilapia Oreochromis niloticus genome based on cytogenetic and genomics/bioinformatics approach. The results showed that some elements are not randomly distributed and that some are genomic dependent on each other. Moreover, we found extensive overlap between genomics and cytogenetics data and that tandem duplication may be the major mechanism responsible for the genomic dynamics of TEs here analyzed. This paper provides insights in the genomic organization of TEs under an integrated view based on cytogenetics and genomics.

  20. Neural Network Prediction of Translation Initiation Sites in Eukaryotes: Perspectives for EST and Genome analysis

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Nielsen, Henrik

    1997-01-01

    Translation in eukaryotes does not always start at the first AUG in an mRNA, implying that context information also plays a role.This makes prediction of translation initiation sites a non-trivial task, especially when analysing EST and genome data where the entire mature mRNA sequence is not known...... and global sequence information. Furthermore, analysis of false predictions shows that AUGs in frame with the actual start codon are more frequently selected than out-of-frame AUGs, suggesting that our nteworks use reading frame detection. A number of conflicts between neural network predictions and database...... annotations are analysed in detail, leading to identification of possible database errors....

  1. A self-organized artificial neural network architecture for sensory integration with applications to letter-phoneme integration.

    Science.gov (United States)

    Jantvik, Tamas; Gustafsson, Lennart; Papliński, Andrew P

    2011-08-01

    The multimodal self-organizing network (MMSON), an artificial neural network architecture carrying out sensory integration, is presented here. The architecture is designed using neurophysiological findings and imaging studies that pertain to sensory integration and consists of interconnected lattices of artificial neurons. In this artificial neural architecture, the degree of recognition of stimuli, that is, the perceived reliability of stimuli in the various subnetworks, is included in the computation. The MMSON's behavior is compared to aspects of brain function that deal with sensory integration. According to human behavioral studies, integration of signals from sensory receptors of different modalities enhances perception of objects and events and also reduces time to detection. In neocortex, integration takes place in bimodal and multimodal association areas and result, not only in feedback-mediated enhanced unimodal perception and shortened reaction time, but also in robust bimodal or multimodal percepts. Simulation data from the presented artificial neural network architecture show that it replicates these important psychological and neuroscientific characteristics of sensory integration.

  2. A New Era of Genome Integration-Simply Cut and Paste!

    Science.gov (United States)

    Liu, Zihe; Liang, Youyun; Ang, Ee Lui; Zhao, Huimin

    2017-01-24

    Genome integration is a powerful tool in both basic and applied biological research. However, traditional genome integration, which is typically mediated by homologous recombination, has been constrained by low efficiencies and limited host range. In recent years, the emergence of homing endonucleases and programmable nucleases has greatly enhanced integration efficiencies and allowed alternative integration mechanisms such as nonhomologous end joining and microhomology-mediated end joining, enabling integration in hosts deficient in homologous recombination. In this review, we will highlight recent advances and breakthroughs in genome integration methods made possible by programmable nucleases, and their new applications in synthetic biology and metabolic engineering.

  3. IMG 4 version of the integrated microbial genomes comparative analysis system

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, Victor M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Chen, I-Min A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Palaniappan, Krishna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Chu, Ken [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Szeto, Ernest [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Pillay, Manoj [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Ratner, Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Huang, Jinghua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Data Management and Technology Center. Computational Research Division; Woyke, Tanja [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Huntemann, Marcel [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Anderson, Iain [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Billis, Konstantinos [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Varghese, Neha [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Mavromatis, Konstantinos [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Pati, Amrita [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Ivanova, Natalia N. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program; Kyrpides, Nikos C. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States). Microbial Genome and Metagenome Program

    2013-10-27

    The Integrated Microbial Genomes (IMG) data warehouse integrates genomes from all three domains of life, as well as plasmids, viruses and genome fragments. IMG provides tools for analyzing and reviewing the structural and functional annotations of genomes in a comparative context. IMG’s data content and analytical capabilities have increased continuously since its first version released in 2005. Since the last report published in the 2012 NAR Database Issue, IMG’s annotation and data integration pipelines have evolved while new tools have been added for recording and analyzing single cell genomes, RNA Seq and biosynthetic cluster data. Finally, different IMG datamarts provide support for the analysis of publicly available genomes (IMG/W: http://img.jgi.doe.gov/w), expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er) and teaching and training in the area of microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu).

  4. IMG 4 version of the integrated microbial genomes comparative analysis system.

    Science.gov (United States)

    Markowitz, Victor M; Chen, I-Min A; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Pillay, Manoj; Ratner, Anna; Huang, Jinghua; Woyke, Tanja; Huntemann, Marcel; Anderson, Iain; Billis, Konstantinos; Varghese, Neha; Mavromatis, Konstantinos; Pati, Amrita; Ivanova, Natalia N; Kyrpides, Nikos C

    2014-01-01

    The Integrated Microbial Genomes (IMG) data warehouse integrates genomes from all three domains of life, as well as plasmids, viruses and genome fragments. IMG provides tools for analyzing and reviewing the structural and functional annotations of genomes in a comparative context. IMG's data content and analytical capabilities have increased continuously since its first version released in 2005. Since the last report published in the 2012 NAR Database Issue, IMG's annotation and data integration pipelines have evolved while new tools have been added for recording and analyzing single cell genomes, RNA Seq and biosynthetic cluster data. Different IMG datamarts provide support for the analysis of publicly available genomes (IMG/W: http://img.jgi.doe.gov/w), expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er) and teaching and training in the area of microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu).

  5. Crossmodal integration enhances neural representation of task-relevant features in audiovisual face perception.

    Science.gov (United States)

    Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Liu, Yongjian; Liang, Changhong; Sun, Pei

    2015-02-01

    Previous studies have shown that audiovisual integration improves identification performance and enhances neural activity in heteromodal brain areas, for example, the posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG). Furthermore, it has also been demonstrated that attention plays an important role in crossmodal integration. In this study, we considered crossmodal integration in audiovisual facial perception and explored its effect on the neural representation of features. The audiovisual stimuli in the experiment consisted of facial movie clips that could be classified into 2 gender categories (male vs. female) or 2 emotion categories (crying vs. laughing). The visual/auditory-only stimuli were created from these movie clips by removing the auditory/visual contents. The subjects needed to make a judgment about the gender/emotion category for each movie clip in the audiovisual, visual-only, or auditory-only stimulus condition as functional magnetic resonance imaging (fMRI) signals were recorded. The neural representation of the gender/emotion feature was assessed using the decoding accuracy and the brain pattern-related reproducibility indices, obtained by a multivariate pattern analysis method from the fMRI data. In comparison to the visual-only and auditory-only stimulus conditions, we found that audiovisual integration enhanced the neural representation of task-relevant features and that feature-selective attention might play a role of modulation in the audiovisual integration.

  6. Path integration and the neural basis of the 'cognitive map'.

    NARCIS (Netherlands)

    McNaughton, B.L.; Battaglia, F.P.; Jensen, O.; Moser, E.I.; Moser, M.B

    2006-01-01

    The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might pe

  7. Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism

    DEFF Research Database (Denmark)

    Hu, Zheng; Zhu, Da; Wang, Wei

    2015-01-01

    Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis1. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas...

  8. GDR (Genome Database for Rosaceae): integrated web-database for Rosaceae genomics and genetics data.

    Science.gov (United States)

    Jung, Sook; Staton, Margaret; Lee, Taein; Blenda, Anna; Svancara, Randall; Abbott, Albert; Main, Dorrie

    2008-01-01

    The Genome Database for Rosaceae (GDR) is a central repository of curated and integrated genetics and genomics data of Rosaceae, an economically important family which includes apple, cherry, peach, pear, raspberry, rose and strawberry. GDR contains annotated databases of all publicly available Rosaceae ESTs, the genetically anchored peach physical map, Rosaceae genetic maps and comprehensively annotated markers and traits. The ESTs are assembled to produce unigene sets of each genus and the entire Rosaceae. Other annotations include putative function, microsatellites, open reading frames, single nucleotide polymorphisms, gene ontology terms and anchored map position where applicable. Most of the published Rosaceae genetic maps can be viewed and compared through CMap, the comparative map viewer. The peach physical map can be viewed using WebFPC/WebChrom, and also through our integrated GDR map viewer, which serves as a portal to the combined genetic, transcriptome and physical mapping information. ESTs, BACs, markers and traits can be queried by various categories and the search result sites are linked to the mapping visualization tools. GDR also provides online analysis tools such as a batch BLAST/FASTA server for the GDR datasets, a sequence assembly server and microsatellite and primer detection tools. GDR is available at http://www.rosaceae.org.

  9. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Directory of Open Access Journals (Sweden)

    Bodour Salhia

    Full Text Available The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  10. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Science.gov (United States)

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T D; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N; DiPerna, Danielle M; Paquette, Kimberly M; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F; Liotta, Lance A; Ramanathan, Ramesh K; Berens, Michael E; Tran, Nhan L

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  11. Sensorimotor Integration in Speech Processing: Computational Basis and Neural Organization

    National Research Council Canada - National Science Library

    Hickok, Gregory; Houde, John; Rong, Feng

    2011-01-01

    .... We propose an integrative model of the speech-related "dorsal stream" in which sensorimotor interaction primarily supports speech production, in the form of a state feedback control architecture...

  12. Modeling electrocortical activity through improved local approximations of integral neural field equations.

    NARCIS (Netherlands)

    Coombes, S.; Venkov, N.A.; Shiau, L.; Bojak, I.; Liley, D.T.; Laing, C.R.

    2007-01-01

    Neural field models of firing rate activity typically take the form of integral equations with space-dependent axonal delays. Under natural assumptions on the synaptic connectivity we show how one can derive an equivalent partial differential equation (PDE) model that properly treats the axonal dela

  13. Crossmodal deficit in dyslexic children : practice affects the neural timing of letter-speech sound integration

    NARCIS (Netherlands)

    Žarić, G.; Fraga González, G.; Tijms, J.; van der Molen, M.W.; Blomert, L.; Bonte, M.

    2015-01-01

    A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills

  14. Neural basis of limb ownership in individuals with body integrity identity disorder

    NARCIS (Netherlands)

    van Dijk, M.T.; van Wingen, G.A.; van Lammeren, A.; Blom, R.M.; de Kwaasteniet, B.P.; Scholte, H.S.; Denys, D.

    2013-01-01

    Our body feels like it is ours. However, individuals with body integrity identity disorder (BIID) lack this feeling of ownership for distinct limbs and desire amputation of perfectly healthy body parts. This extremely rare condition provides us with an opportunity to study the neural basis underlyin

  15. Molecular Assemblies, Genes and Genomics Integrated Efficiently (MAGGIE)

    Energy Technology Data Exchange (ETDEWEB)

    Baliga, Nitin S

    2011-05-26

    when applied to the manually curated training set. Applying this method to the data representing around a quarter of the fraction space for water soluble proteins in D. vulgaris, we obtained 854 reliable pair wise interactions. Further, we have developed algorithms to analyze and assign significance to protein interaction data from bait pull-down experiments and integrate these data with other systems biology data through associative biclustering in a parallel computing environment. We will 'fill-in' missing information in these interaction data using a 'Transitive Closure' algorithm and subsequently use 'Between Commonality Decomposition' algorithm to discover complexes within these large graphs of protein interactions. To characterize the metabolic activities of proteins and their complexes we are developing algorithms to deconvolute pure mass spectra, estimate chemical formula for m/z values, and fit isotopic fine structure to metabolomics data. We have discovered that in comparison to isotopic pattern fitting methods restricting the chemical formula by these two dimensions actually facilitates unique solutions for chemical formula generators. To understand how microbial functions are regulated we have developed complementary algorithms for reconstructing gene regulatory networks (GRNs). Whereas the network inference algorithms cMonkey and Inferelator developed enable de novo reconstruction of predictive models for GRNs from diverse systems biology data, the RegPrecise and RegPredict framework developed uses evolutionary comparisons of genomes from closely related organisms to reconstruct conserved regulons. We have integrated the two complementary algorithms to rapidly generate comprehensive models for gene regulation of understudied organisms. Our preliminary analyses of these reconstructed GRNs have revealed novel regulatory mechanisms and cis-regulatory motifs, as well asothers that are conserved across species. Finally, we are

  16. The integrated web service and genome database for agricultural plants with biotechnology information

    Science.gov (United States)

    Kim, ChangKug; Park, DongSuk; Seol, YoungJoo; Hahn, JangHo

    2011-01-01

    The National Agricultural Biotechnology Information Center (NABIC) constructed an agricultural biology-based infrastructure and developed a Web based relational database for agricultural plants with biotechnology information. The NABIC has concentrated on functional genomics of major agricultural plants, building an integrated biotechnology database for agro-biotech information that focuses on genomics of major agricultural resources. This genome database provides annotated genome information from 1,039,823 records mapped to rice, Arabidopsis, and Chinese cabbage. PMID:21887015

  17. Integrating multiple sensory systems to modulate neural networks controlling posture.

    Science.gov (United States)

    Lavrov, I; Gerasimenko, Y; Burdick, J; Zhong, H; Roy, R R; Edgerton, V R

    2015-12-01

    In this study we investigated the ability of sensory input to produce tonic responses in hindlimb muscles to facilitate standing in adult spinal rats and tested two hypotheses: 1) whether the spinal neural networks below a complete spinal cord transection can produce tonic reactions by activating different sensory inputs and 2) whether facilitation of tonic and rhythmic responses via activation of afferents and with spinal cord stimulation could engage similar neuronal mechanisms. We used a dynamically controlled platform to generate vibration during weight bearing, epidural stimulation (at spinal cord level S1), and/or tail pinching to determine the postural control responses that can be generated by the lumbosacral spinal cord. We observed that a combination of platform displacement, epidural stimulation, and tail pinching produces a cumulative effect that progressively enhances tonic responses in the hindlimbs. Tonic responses produced by epidural stimulation alone during standing were represented mainly by monosynaptic responses, whereas the combination of epidural stimulation and tail pinching during standing or epidural stimulation during stepping on a treadmill facilitated bilaterally both monosynaptic and polysynaptic responses. The results demonstrate that tonic muscle activity after complete spinal cord injury can be facilitated by activation of specific combinations of afferent inputs associated with load-bearing proprioception and cutaneous input in the presence of epidural stimulation and indicate that whether activation of tonic or rhythmic responses is generated depends on the specific combinations of sources and types of afferents activated in the hindlimb muscles.

  18. An integrative neural model of social perception, action observation, and theory of mind.

    Science.gov (United States)

    Yang, Daniel Y-J; Rosenblau, Gabriela; Keifer, Cara; Pelphrey, Kevin A

    2015-04-01

    In the field of social neuroscience, major branches of research have been instrumental in describing independent components of typical and aberrant social information processing, but the field as a whole lacks a comprehensive model that integrates different branches. We review existing research related to the neural basis of three key neural systems underlying social information processing: social perception, action observation, and theory of mind. We propose an integrative model that unites these three processes and highlights the posterior superior temporal sulcus (pSTS), which plays a central role in all three systems. Furthermore, we integrate these neural systems with the dual system account of implicit and explicit social information processing. Large-scale meta-analyses based on Neurosynth confirmed that the pSTS is at the intersection of the three neural systems. Resting-state functional connectivity analysis with 1000 subjects confirmed that the pSTS is connected to all other regions in these systems. The findings presented in this review are specifically relevant for psychiatric research especially disorders characterized by social deficits such as autism spectrum disorder.

  19. An integrative neural model of social perception, action observation, and theory of mind

    Science.gov (United States)

    Yang, Daniel Y.-J.; Rosenblau, Gabriela; Keifer, Cara; Pelphrey, Kevin A.

    2016-01-01

    In the field of social neuroscience, major branches of research have been instrumental in describing independent components of typical and aberrant social information processing, but the field as a whole lacks a comprehensive model that integrates different branches. We review existing research related to the neural basis of three key neural systems underlying social information processing: social perception, action observation, and theory of mind. We propose an integrative model that unites these three processes and highlights the posterior superior temporal sulcus (pSTS), which plays a central role in all three systems. Furthermore, we integrate these neural systems with the dual system account of implicit and explicit social information processing. Large-scale meta-analyses based on Neurosynth confirmed that the pSTS is at the intersection of the three neural systems. Resting-state functional connectivity analysis with 1000 subjects confirmed that the pSTS is connected to all other regions in these systems. The findings presented in this review are specifically relevant for psychiatric research especially disorders characterized by social deficits such as autism spectrum disorder. PMID:25660957

  20. A tale of two species: Neural integration in zebrafish and monkeys.

    Science.gov (United States)

    Joshua, M; Lisberger, S G

    2015-06-18

    Selection of a model organism creates tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called "neural integration" that occurs in the brainstems of larval zebrafish, primates, and species "in between". We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone.

  1. Information maintenance in working memory: an integrated presentation of cognitive and neural concepts.

    Science.gov (United States)

    Martini, Markus; Furtner, Marco R; Maran, Thomas; Sachse, Pierre

    2015-01-01

    Working memory (WM) maintains information in a state that it is available for processing. A host of various concepts exist which define this core function at different levels of abstraction. The present article intended to bring together existing cognitive and neural explanatory approaches about the architecture and neural mechanisms of information maintenance in WM. For this, we highlight how existing WM concepts define information retention and present different methodological approaches which led to the assumption that information can exist in various components and states. This view is broadened by neural concepts focussing on various forms of phase synchronization and molecular biological mechanisms relevant for retaining information in an active state. An integrated presentation of different concepts and methodological approaches can deepen our understanding of this central WM function.

  2. The Integrated Microbial Genomes (IMG) System: An Expanding Comparative Analysis Resource

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Grechkin, Yuri; Ratner, Anna; Anderson, Iain; Lykidis, Athanasios; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2009-09-13

    The integrated microbial genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG contains both draft and complete microbial genomes integrated with other publicly available genomes from all three domains of life, together with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. Since its first release in 2005, IMG's data content and analytical capabilities have been constantly expanded through regular releases. Several companion IMG systems have been set up in order to serve domain specific needs, such as expert review of genome annotations. IMG is available at .

  3. Compromised genomic integrity impedes muscle growth after Atrx inactivation.

    Science.gov (United States)

    Huh, Michael S; Price O'Dea, Tina; Ouazia, Dahmane; McKay, Bruce C; Parise, Gianni; Parks, Robin J; Rudnicki, Michael A; Picketts, David J

    2012-12-01

    ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle-specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late-replicating chromatin, and its loss resulted in rampant signs of genomic instability. These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue.

  4. Neural Network Emulation of the Integral Equation Model with Multiple Scattering

    Directory of Open Access Journals (Sweden)

    Luca Pulvirenti

    2009-10-01

    Full Text Available The Integral Equation Model with multiple scattering (IEMM represents a well-established method that provides a theoretical framework for the scattering of electromagnetic waves from rough surfaces. A critical aspect is the long computational time required to run such a complex model. To deal with this problem, a neural network technique is proposed in this work. In particular, we have adopted neural networks to reproduce the backscattering coefficients predicted by IEMM at L- and C-bands, thus making reference to presently operative satellite radar sensors, i.e., that aboard ERS-2, ASAR on board ENVISAT (C-band, and PALSAR aboard ALOS (L-band. The neural network-based model has been designed for radar observations of both flat and tilted surfaces, in order to make it applicable for hilly terrains too. The assessment of the proposed approach has been carried out by comparing neural network-derived backscattering coefficients with IEMM-derived ones. Different databases with respect to those employed to train the networks have been used for this purpose. The outcomes seem to prove the feasibility of relying on a neural network approach to efficiently and reliably approximate an electromagnetic model of surface scattering.

  5. A multi-channel fully differential programmable integrated circuit for neural recording application

    Science.gov (United States)

    Yun, Gui; Xu, Zhang; Yuan, Wang; Ming, Liu; Weihua, Pei; Kai, Liang; Suibiao, Huang; Bin, Li; Hongda, Chen

    2013-10-01

    A multi-channel, fully differential programmable chip for neural recording application is presented. The integrated circuit incorporates eight neural recording amplifiers with tunable bandwidth and gain, eight 4th-order Bessel switch capacitor filters, an 8-to-1 analog time-division multiplexer, a fully differential successive approximation register analog-to-digital converter (SAR ADC), and a serial peripheral interface for communication. The neural recording amplifier presents a programmable gain from 53 dB to 68 dB, a tunable low cut-off frequency from 0.1 Hz to 300 Hz, and 3.77 μVrms input-referred noise over a 5 kHz bandwidth. The SAR ADC digitizes signals at maximum sampling rate of 20 kS/s per channel and achieves an ENOB of 7.4. The integrated circuit is designed and fabricated in 0.18-μm CMOS mix-signal process. We successfully performed a multi-channel in-vivo recording experiment from a rat cortex using the neural recording chip.

  6. Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson's Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations

    DEFF Research Database (Denmark)

    Momcilovic, Olga; Sivapatham, Renuka; Oron, Tal Ronnen

    2016-01-01

    We report generation of induced pluripotent stem cell (iPSC) lines from ten Parkinson's disease (PD) patients carrying SNCA, PARK2, LRRK2, and GBA mutations, and one age-matched control. After validation of pluripotency, long-term genome stability, and integration-free reprogramming, eight...... of these lines (one of each SNCA, LRRK2 and GBA, four PARK2 lines, and the control) were differentiated into neural stem cells (NSC) and subsequently to dopaminergic cultures. We did not observe significant differences in the timeline of neural induction and NSC derivation between the patient and control line...... to identify alterations by large-scale evaluation. While gene expression profiling clearly distinguished cells at different stages of differentiation, no mutation-specific clustering or difference was observed, though consistent changes in patient lines were detected in genes associated mitochondrial biology...

  7. Integrating genetics and genomics into nursing curricula: you can do it too!

    Science.gov (United States)

    Daack-Hirsch, Sandra; Jackson, Barbara; Belchez, Chito A; Elder, Betty; Hurley, Roxanne; Kerr, Peg; Nissen, Mary Kay

    2013-12-01

    Rapid advances in knowledge and technology related to genomics cross health care disciplines and touch almost every aspect of patient care. The ability to sequence a genome holds the promise that health care can be personalized. Health care professionals are faced with a gap in the ability to use the rapidly expanding technology and knowledge related to genomics in practice. Yet, nurses are key to bridging the gap between genomic discoveries and the human experience of illness. This article presents a case study documenting the experience of five nursing schools/colleges of nursing as they work to integrate genetics and genomics into their curricula.

  8. Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation.

    Science.gov (United States)

    Kaufer, Benedikt B; Jarosinski, Keith W; Osterrieder, Nikolaus

    2011-03-14

    Some herpesviruses, particularly lymphotropic viruses such as Marek's disease virus (MDV) and human herpesvirus 6 (HHV-6), integrate their DNA into host chromosomes. MDV and HHV-6, among other herpesviruses, harbor telomeric repeats (TMRs) identical to host telomeres at either end of their linear genomes. Using MDV as a natural virus-host model, we show that herpesvirus TMRs facilitate viral genome integration into host telomeres and that integration is important for establishment of latency and lymphoma formation. Integration into host telomeres also aids in reactivation from the quiescent state of infection. Our results and the presence of TMRs in many herpesviruses suggest that integration mediated by viral TMRs is a conserved mechanism, which ensures faithful virus genome maintenance in host cells during cell division and allows efficient mobilization of dormant viral genomes. This finding is of particular importance as reactivation is critical for virus spread between susceptible individuals and is necessary for continued herpesvirus evolution and survival.

  9. Stakeholder engagement: a key component of integrating genomic information into electronic health records.

    Science.gov (United States)

    Hartzler, Andrea; McCarty, Catherine A; Rasmussen, Luke V; Williams, Marc S; Brilliant, Murray; Bowton, Erica A; Clayton, Ellen Wright; Faucett, William A; Ferryman, Kadija; Field, Julie R; Fullerton, Stephanie M; Horowitz, Carol R; Koenig, Barbara A; McCormick, Jennifer B; Ralston, James D; Sanderson, Saskia C; Smith, Maureen E; Trinidad, Susan Brown

    2013-10-01

    Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.

  10. Neural mechanisms underlying the integration of situational information into attribution outcomes

    OpenAIRE

    Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S.; Phelps, Elizabeth A.

    2013-01-01

    When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e. personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately...

  11. Neural mechanisms underlying the integration of situational information into attribution outcomes

    OpenAIRE

    Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S.; Phelps, Elizabeth A.

    2013-01-01

    When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e. personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately...

  12. Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2015-06-01

    Full Text Available Human immunodeficiency virus (HIV-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS, which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

  13. Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome.

    Science.gov (United States)

    Liu, Qiang; Wang, Xue-Feng; Ma, Jian; He, Xi-Jun; Wang, Xiao-Jun; Zhou, Jian-Hua

    2015-06-19

    Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

  14. Sinbase: an integrated database to study genomics, genetics and comparative genomics in Sesamum indicum.

    Science.gov (United States)

    Wang, Linhai; Yu, Jingyin; Li, Donghua; Zhang, Xiurong

    2015-01-01

    Sesame (Sesamum indicum L.) is an ancient and important oilseed crop grown widely in tropical and subtropical areas. It belongs to the gigantic order Lamiales, which includes many well-known or economically important species, such as olive (Olea europaea), leonurus (Leonurus japonicus) and lavender (Lavandula spica), many of which have important pharmacological properties. Despite their importance, genetic and genomic analyses on these species have been insufficient due to a lack of reference genome information. The now available S. indicum genome will provide an unprecedented opportunity for studying both S. indicum genetic traits and comparative genomics. To deliver S. indicum genomic information to the worldwide research community, we designed Sinbase, a web-based database with comprehensive sesame genomic, genetic and comparative genomic information. Sinbase includes sequences of assembled sesame pseudomolecular chromosomes, protein-coding genes (27,148), transposable elements (372,167) and non-coding RNAs (1,748). In particular, Sinbase provides unique and valuable information on colinear regions with various plant genomes, including Arabidopsis thaliana, Glycine max, Vitis vinifera and Solanum lycopersicum. Sinbase also provides a useful search function and data mining tools, including a keyword search and local BLAST service. Sinbase will be updated regularly with new features, improvements to genome annotation and new genomic sequences, and is freely accessible at http://ocri-genomics.org/Sinbase/.

  15. A model for integrating elementary neural functions into delayed-response behavior.

    Directory of Open Access Journals (Sweden)

    Thomas Gisiger

    2006-04-01

    Full Text Available It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning, and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task, or recalling from this image another one that has been associated with it during training (delayed-pair association task. The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  16. The Populus Genome Integrative Explorer (PopGenIE): a new resource for exploring the Populus genome.

    Science.gov (United States)

    Sjödin, Andreas; Street, Nathaniel Robert; Sandberg, Göran; Gustafsson, Petter; Jansson, Stefan

    2009-06-01

    Populus has become an important model plant system. However, utilization of the increasingly extensive collection of genetics and genomics data created by the community is currently hindered by the lack of a central resource, such as a model organism database (MOD). Such MODs offer a single entry point to the collection of resources available within a model system, typically including tools for exploring and querying those resources. As a starting point to overcoming the lack of such an MOD for Populus, we present the Populus Genome Integrative Explorer (PopGenIE), an integrated set of tools for exploring the Populus genome and transcriptome. The resource includes genome, synteny and quantitative trait locus (QTL) browsers for exploring genetic data. Expression tools include an electronic fluorescent pictograph (eFP) browser, expression profile plots, co-regulation within collated transcriptomics data sets, and identification of over-represented functional categories and genomic hotspot locations. A number of collated transcriptomics data sets are made available in the eFP browser to facilitate functional exploration of gene function. Additional homology and data extraction tools are provided. PopGenIE significantly increases accessibility to Populus genomics resources and allows exploration of transcriptomics data without the need to learn or understand complex statistical analysis methods. PopGenIE is available at www.popgenie.org or via www.populusgenome.info.

  17. Stability analysis of delayed neural networks via a new integral inequality.

    Science.gov (United States)

    Yang, Bin; Wang, Juan; Wang, Jun

    2017-04-01

    This paper focuses on stability analysis for neural networks systems with time-varying delays. A more general auxiliary function-based integral inequality is established and some improved delay-dependent stability conditions formulated in terms of linear matrix inequalities (LMIs) are derived by employing a suitable Lyapunov-Krasovskii functional (LKF) and the novel integral inequality. Three well-known application examples are provided to demonstrate the effectiveness and improvements of the proposed method. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The three-dimensional genome organization of Drosophila melanogaster through data integration.

    Science.gov (United States)

    Li, Qingjiao; Tjong, Harianto; Li, Xiao; Gong, Ke; Zhou, Xianghong Jasmine; Chiolo, Irene; Alber, Frank

    2017-07-31

    Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome's organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.

  19. Reverse gyrase functions in genome integrity maintenance by protecting DNA breaks in vivo

    DEFF Research Database (Denmark)

    Han, Wenyuan; Feng, Xu; She, Qunxin

    2017-01-01

    Reverse gyrase introduces positive supercoils to circular DNA and is implicated in genome stability maintenance in thermophiles. The extremely thermophilic crenarchaeon Sulfolobus encodes two reverse gyrase proteins, TopR1 (topoisomerase reverse gyrase 1) and TopR2, whose functions in thermophili...... genomic DNA degradation during MMS treatment, accompanied by a higher rate of cell death. Taken together, these results indicate that TopR1 probably facilitates genome integrity maintenance by protecting DNA breaks from thermo-degradation in vivo....

  20. An integrated computational pipeline and database to support whole-genome sequence annotation.

    Science.gov (United States)

    Mungall, C J; Misra, S; Berman, B P; Carlson, J; Frise, E; Harris, N; Marshall, B; Shu, S; Kaminker, J S; Prochnik, S E; Smith, C D; Smith, E; Tupy, J L; Wiel, C; Rubin, G M; Lewis, S E

    2002-01-01

    We describe here our experience in annotating the Drosophila melanogaster genome sequence, in the course of which we developed several new open-source software tools and a database schema to support large-scale genome annotation. We have developed these into an integrated and reusable software system for whole-genome annotation. The key contributions to overall annotation quality are the marshalling of high-quality sequences for alignments and the design of a system with an adaptable and expandable flexible architecture.

  1. SIGMA2: A system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes

    Directory of Open Access Journals (Sweden)

    MacAulay Calum

    2008-10-01

    Full Text Available Abstract Background High throughput microarray technologies have afforded the investigation of genomes, epigenomes, and transcriptomes at unprecedented resolution. However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed. Results Here, we present SIGMA2, a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes. Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics. Conclusion The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH, DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

  2. Intelligent Sensor Positioning and Orientation Through Constructive Neural Network-Embedded INS/GPS Integration Algorithms

    Directory of Open Access Journals (Sweden)

    Kai-Wei Chiang

    2010-10-01

    Full Text Available Mobile mapping systems have been widely applied for acquiring spatial information in applications such as spatial information systems and 3D city models. Nowadays the most common technologies used for positioning and orientation of a mobile mapping system include a Global Positioning System (GPS as the major positioning sensor and an Inertial Navigation System (INS as the major orientation sensor. In the classical approach, the limitations of the Kalman Filter (KF method and the overall price of multi-sensor systems have limited the popularization of most land-based mobile mapping applications. Although intelligent sensor positioning and orientation schemes consisting of Multi-layer Feed-forward Neural Networks (MFNNs, one of the most famous Artificial Neural Networks (ANNs, and KF/smoothers, have been proposed in order to enhance the performance of low cost Micro Electro Mechanical System (MEMS INS/GPS integrated systems, the automation of the MFNN applied has not proven as easy as initially expected. Therefore, this study not only addresses the problems of insufficient automation in the conventional methodology that has been applied in MFNN-KF/smoother algorithms for INS/GPS integrated systems proposed in previous studies, but also exploits and analyzes the idea of developing alternative intelligent sensor positioning and orientation schemes that integrate various sensors in more automatic ways. The proposed schemes are implemented using one of the most famous constructive neural networks––the Cascade Correlation Neural Network (CCNNs––to overcome the limitations of conventional techniques based on KF/smoother algorithms as well as previously developed MFNN-smoother schemes. The CCNNs applied also have the advantage of a more flexible topology compared to MFNNs. Based on the experimental data utilized the preliminary results presented in this article illustrate the effectiveness of the proposed schemes compared to smoother algorithms

  3. A second generation integrated map of the rainbow trout (Oncorhynchus mykiss) genome: analysis of synteny with model fish genomes

    Science.gov (United States)

    In this paper we generated DNA fingerprints and end sequences from bacterial artificial chromosomes (BACs) from two new libraries to improve the first generation integrated physical and genetic map of the rainbow trout (Oncorhynchus mykiss) genome. The current version of the physical map is compose...

  4. An Integrative Pathway-based Clinical-genomic Model for Cancer Survival Prediction.

    Science.gov (United States)

    Chen, Xi; Wang, Lily; Ishwaran, Hemant

    2010-09-01

    Prediction models that use gene expression levels are now being proposed for personalized treatment of cancer, but building accurate models that are easy to interpret remains a challenge. In this paper, we describe an integrative clinical-genomic approach that combines both genomic pathway and clinical information. First, we summarize information from genes in each pathway using Supervised Principal Components (SPCA) to obtain pathway-based genomic predictors. Next, we build a prediction model based on clinical variables and pathway-based genomic predictors using Random Survival Forests (RSF). Our rationale for this two-stage procedure is that the underlying disease process may be influenced by environmental exposure (measured by clinical variables) and perturbations in different pathways (measured by pathway-based genomic variables), as well as their interactions. Using two cancer microarray datasets, we show that the pathway-based clinical-genomic model outperforms gene-based clinical-genomic models, with improved prediction accuracy and interpretability.

  5. Adaptive Neural Control Based on High Order Integral Chained Differentiator for Morphing Aircraft

    Directory of Open Access Journals (Sweden)

    Zhonghua Wu

    2015-01-01

    Full Text Available This paper presents an adaptive neural control for the longitudinal dynamics of a morphing aircraft. Based on the functional decomposition, it is reasonable to decompose the longitudinal dynamics into velocity and altitude subsystems. As for the velocity subsystem, the adaptive control is proposed via dynamic inversion method using neural network. To deal with input constraints, the additional compensation system is employed to help engine recover from input saturation rapidly. The highlight is that high order integral chained differentiator is used to estimate the newly defined variables and an adaptive neural controller is designed for the altitude subsystem where only one neural network is employed to approximate the lumped uncertain nonlinearity. The altitude subsystem controller is considerably simpler than the ones based on backstepping. It is proved using Lyapunov stability theory that the proposed control law can ensure that all the tracking error converges to an arbitrarily small neighborhood around zero. Numerical simulation study demonstrates the effectiveness of the proposed strategy, during the morphing process, in spite of some uncertain system nonlinearity.

  6. Integration of Online Parameter Identification and Neural Network for In-Flight Adaptive Control

    Science.gov (United States)

    Hageman, Jacob J.; Smith, Mark S.; Stachowiak, Susan

    2003-01-01

    An indirect adaptive system has been constructed for robust control of an aircraft with uncertain aerodynamic characteristics. This system consists of a multilayer perceptron pre-trained neural network, online stability and control derivative identification, a dynamic cell structure online learning neural network, and a model following control system based on the stochastic optimal feedforward and feedback technique. The pre-trained neural network and model following control system have been flight-tested, but the online parameter identification and online learning neural network are new additions used for in-flight adaptation of the control system model. A description of the modification and integration of these two stand-alone software packages into the complete system in preparation for initial flight tests is presented. Open-loop results using both simulation and flight data, as well as closed-loop performance of the complete system in a nonlinear, six-degree-of-freedom, flight validated simulation, are analyzed. Results show that this online learning system, in contrast to the nonlearning system, has the ability to adapt to changes in aerodynamic characteristics in a real-time, closed-loop, piloted simulation, resulting in improved flying qualities.

  7. Anomaly in neural phase coherence accompanies reduced sensorimotor integration in adults who stutter.

    Science.gov (United States)

    Sengupta, Ranit; Shah, Shalin; Gore, Katie; Loucks, Torrey; Nasir, Sazzad M

    2016-12-01

    Despite advances in our understanding of the human speech system, the neurophysiological basis of stuttering remains largely unknown. Here, it is hypothesized that the speech of adults who stutter (AWS) is susceptible to disruptions in sensorimotor integration caused by neural miscommunication within the speech motor system. Human speech unfolds over rapid timescales and relies on a distributed system of brain regions working in a parallel and synchronized manner, and a breakdown in neural communication between the putative brain regions could increase susceptibility to dysfluency. Using a speech motor adaptation paradigm under altered auditory feedback with simultaneous recording of EEG, the oscillatory cortical dynamics was investigated in stuttering and fluent adults (FA). Auditory feedback perturbation involved the shifting of the formant frequencies of the target vowel sound. Reduced adaptation in response to the feedback error was observed in AWS and was accompanied by differences in EEG spectral powers and anomalies in phase coherence evolving over the course of speech motor training. It is understood that phase coherence possibly captures neural communication within speech motor networks. Thus, the phase coherence network of the two groups exhibited differences involving the EEG frequency bands. These findings in anomalous neural synchrony provide novel evidence for compromised neuronal communication at short time scales within the speech motor network of AWS.

  8. Neural Network Aided Adaptive UKF Algorithm for GPS/INS Integration Navigation

    Directory of Open Access Journals (Sweden)

    TAN Xinglong

    2015-04-01

    Full Text Available The predicted residual vectors should be zero-mean Gaussian white noise, which is the precondition for multiple fading factors adaptive filtering algorithm based on statistical information in GPS/INS integration system. However the abnormalities in observations will affect the distribution of the residual vectors. In this paper, a neural network aided adaptive unscented Kalman filter (UKF algorithm with multiple fading factors based on singular value decomposition(SVD is proposed. The algorithm uses the neural network algorithm to weaken the influence of the observed abnormalities on the residual vectors. Singular value decomposition instead of unscented transformation is adopted to suppress negative definite variation in priori covariance matrix of UKF. Since single fading factor in poor tracking of multiple variables has the limitation, multiple fading factors to adjust the predicted-state covariance matrix are constructed with better robustness so that each filter channel has different adjustability. Finally, vehicle measurement data are collected to validate the proposed algorithm. It shows that the neural network algorithm can prevent the observed abnormalities from affecting the distribution of the residual vectors, expanding the applied range of the adaptive algorithm. The neural network algorithm aided SVD-UKF algorithm with multiple fading factors is able to remove influences of state anomalies on condition of the observed abnormalities. The accuracy and reliability of the navigation solution can be improved by this algorithm.

  9. BGI-RIS: an integrated information resource and comparative analysis workbench for rice genomics

    DEFF Research Database (Denmark)

    Zhao, Wenming; Wang, Jing; He, Ximiao

    2004-01-01

    the application of the rice genomic information and to provide a foundation for functional and evolutionary studies of other important cereal crops, we implemented our Rice Information System (BGI-RIS), the most up-to-date integrated information resource as well as a workbench for comparative genomic analysis...

  10. viruSITE—integrated database for viral genomics

    Science.gov (United States)

    Stano, Matej; Beke, Gabor; Klucar, Lubos

    2016-01-01

    Viruses are the most abundant biological entities and the reservoir of most of the genetic diversity in the Earth's biosphere. Viral genomes are very diverse, generally short in length and compared to other organisms carry only few genes. viruSITE is a novel database which brings together high-value information compiled from various resources. viruSITE covers the whole universe of viruses and focuses on viral genomes, genes and proteins. The database contains information on virus taxonomy, host range, genome features, sequential relatedness as well as the properties and functions of viral genes and proteins. All entries in the database are linked to numerous information resources. The above-mentioned features make viruSITE a comprehensive knowledge hub in the field of viral genomics. The web interface of the database was designed so as to offer an easy-to-navigate, intuitive and user-friendly environment. It provides sophisticated text searching and a taxonomy-based browsing system. viruSITE also allows for an alternative approach based on sequence search. A proprietary genome browser generates a graphical representation of viral genomes. In addition to retrieving and visualising data, users can perform comparative genomics analyses using a variety of tools. Database URL: http://www.virusite.org/ PMID:28025349

  11. Generation of human induced pluripotent stem cells using genome integrating or non-integrating methods.

    Science.gov (United States)

    Šimara, P; Tesařová, L; Padourová, S; Koutná, I

    2014-01-01

    Preclinical studies have demonstrated the promising potential of human induced pluripotent stem cells (hiPSCs) for clinical application. To fulfil this goal, efficient and safe methods to generate them must be established. Various reprogramming techniques were presented during seven years of hiPSCs research. Genome non-integrating and completely xeno-free protocols from the first biopsy to stable hiPSC clones are highly preferable in terms of future clinical application. In this short communication, we summarize the reprogramming experiments performed in our laboratories. We successfully generated hiPSCs using STEMCCA lentivirus, Sendai virus or episomal vectors. Human neonatal fibroblasts and CD34(+) blood progenitors were used as cell sources and were maintained either on mouse embryonic feeder cells or in feeder-free conditions. The reprogramming efficiency was comparable for all three methods and both cell types, while the best results were obtained in feeder-free conditions.

  12. Genomic Integrity Detection of In Vitro Irradiated Banana Using Microsatellite Marker.

    OpenAIRE

    Nina Ratna Djuita; Rita Megia

    2010-01-01

    Genomic Integrity Detection of In Vitro Irradiated Banana Using Microsatellite Marker. The research aims todetect genomic integrity of in vitro irradiated banana using microsatellite marker. These studies were done on bananacv. Pisang Mas irradiated by 15 Gy of gamma ray. The DNA was isolated from each accesion following Dixie.Amplification of DNA products were done by Perkin Elmer Gene Amp PCR 2400 using ten primers, and thenelectroforesis in agarose 1%. Finally a vertical polyacrylamide gel...

  13. DO DYNAMIC NEURAL NETWORKS STAND A BETTER CHANCE IN FRACTIONALLY INTEGRATED PROCESS FORECASTING?

    Directory of Open Access Journals (Sweden)

    Majid Delavari

    2013-04-01

    Full Text Available The main purpose of the present study was to investigate the capabilities of two generations of models such as those based on dynamic neural network (e.g., Nonlinear Neural network Auto Regressive or NNAR model and a regressive (Auto Regressive Fractionally Integrated Moving Average model which is based on Fractional Integration Approach in forecasting daily data related to the return index of Tehran Stock Exchange (TSE. In order to compare these models under similar conditions, Mean Square Error (MSE and also Root Mean Square Error (RMSE were selected as criteria for the models’ simulated out-of-sample forecasting performance. Besides, fractal markets hypothesis was examined and according to the findings, fractal structure was confirmed to exist in the time series under investigation. Another finding of the study was that dynamic artificial neural network model had the best performance in out-of-sample forecasting based on the criteria introduced for calculating forecasting error in comparison with the ARFIMA model.

  14. A multichannel integrated circuit for electrical recording of neural activity, with independent channel programmability.

    Science.gov (United States)

    Mora Lopez, Carolina; Prodanov, Dimiter; Braeken, Dries; Gligorijevic, Ivan; Eberle, Wolfgang; Bartic, Carmen; Puers, Robert; Gielen, Georges

    2012-04-01

    Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR > 60 dB, a THD < 1% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 μA per channel from a single 3.3 V. The ASIC was implemented in a 0.35 μm CMOS technology and has a total area of 5.6 × 4.5 mm². The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios.

  15. Rainfall-runoff modeling at Jinsha River basin by integrated neural network with discrete wavelet transform

    Science.gov (United States)

    Tayyab, Muhammad; Zhou, Jianzhong; Dong, Xiaohua; Ahmad, Ijaz; Sun, Na

    2017-09-01

    Artificial neural network (ANN) models combined with time series decomposition are widely employed to calculate the river flows; however, the influence of the application of diverse decomposing approaches on assessing correctness is inadequately compared and examined. This study investigates the certainty of monthly streamflow by applying ANNs including feed forward back propagation neural network and radial basis function neural network (RBFNN) models integrated with discrete wavelet transform (DWT), at Jinsha River basin in the upper reaches of Yangtze River of China. The effect of the noise factor of the decomposed time series on the prediction correctness has also been argued in this paper. Data have been analyzed by comparing the simulation outputs of the models with the correlation coefficient (R) root mean square errors, mean absolute errors, mean absolute percentage error and Nash-Sutcliffe Efficiency. Results show that time series decomposition technique DWT contributes in improving the accuracy of streamflow prediction, as compared to single ANN's. The detailed comparative analysis showed that the RBFNN integrated with DWT has better forecasting capabilities as compared to other developed models. Moreover, for high-precision streamflow prediction, the high-frequency section of the original time series is very crucial, which is understandable in flood season.

  16. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    NEALSON, KENNETH H.

    2013-10-15

    products of dissimilatory iron reduction. Geochim. Cosmochim. Acta. 74:574-583. 10. Karpinets, T.V., A.Y Obraztsova, Y. Wang, D.D. Schmoyer, G.H. Kora, B.H. Park, M.H. Serres, M.F. Ropmine, M.L. Land, T.B. Kothe, J.K. Fredrickson, K.H. Nealson, and E.C. Uberbacher 2010. Conserved synteny at the protein family level reveals genes underlying Shewanella species? cold tolerance and predicts their novel phenotypes. Funct. Integr. Genomics 10: 97 ? 110. (DOI 10.1007/s10143-009-0142-y) 11. Bretschger, O., A.C.M. Cheung, F. Mansfeld, and K.H. Nealson. 2010. Comparative microbial fuel cell evaluations of Shewanella spp. Electroanalysis 22: 883-894. 12. McLean, J.S., G. Wanger, Y.A. Gorby, M. Wainstein, J. McQuaid, Shun?ichi Ishii, O. Bretschger, H. Beyanal, K.H. Nealson. 2010. Quantification of electron transfer rates to a solid phase electron acceptor through the stages of biofilm formation from single cells to multicellular communities. Env. Sci. Technol. 44:2721-2717. 13. El-Naggar, M., G. Wanger, K.M. Leung, T.D. Yuzvinsky, G. Southam, J. Yang, W.M. Lau, K.H. Nealson, and Y.A. Gorby. 2010. Electrical Transport Along Bacterial Nanowires from Shewanella oneidensis MR-1 Proc. Nat. Acad. Sci. USA 107:18127-18131. 14. Biffinger, J.C., L.A. Fitzgerald, R. Ray, B.J. Little, S.E. Lizewski, E.R. Petersen, B.R. Ringeisen, W.C. Sanders, P.E. Sheehan, J.J. Pietron, J.W. Baldwin, L.J. Nadeau, G.R. Johnson, M. Ribbens, S.E. Finkel, K.H. Nealson. 2010. The utility of Shewanella japonica for microbial fuel cells. Bioresource Technol. 102:290-297. 15. Rodionov, D. , C. Yang, X. Li, I. Rodionova, Y. Wang, A.Y. Obraztsova, O. P. Zagnitko, R. Overbeek, M. F. Romine, S. Reed, J.K. Fredrickson, K.H. Nealson, A.L. Osterman. 2010. Genomic encyclopedia of sugar utilization pathways in the Shewanella genus. BMC Genomics 2010, 11:494 16. Kan, J., L. Hsu, A.C.M. Cheung, M. Pirbazari, and K.H. Nealson. 2011. Current production by bacterial communities in microbial fuel cells enriched from wastewater sludge

  17. Crossmodal deficit in dyslexic children: practice affects the neural timing of letter-speech sound integration.

    Science.gov (United States)

    Žarić, Gojko; Fraga González, Gorka; Tijms, Jurgen; van der Molen, Maurits W; Blomert, Leo; Bonte, Milene

    2015-01-01

    A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills remains unknown. In this research, we examined changes in event-related potential (ERP) measures of letter-speech sound integration over a 6-month period during which 9-year-old dyslexic readers (n = 17) followed a training in letter-speech sound coupling next to their regular reading curriculum. We presented the Dutch spoken vowels /a/ and /o/ as standard and deviant stimuli in one auditory and two audiovisual oddball conditions. In one audiovisual condition (AV0), the letter "a" was presented simultaneously with the vowels, while in the other (AV200) it was preceding vowel onset for 200 ms. Prior to the training (T1), dyslexic readers showed the expected pattern of typical auditory mismatch responses, together with the absence of letter-speech sound effects in a late negativity (LN) window. After the training (T2), our results showed earlier (and enhanced) crossmodal effects in the LN window. Most interestingly, earlier LN latency at T2 was significantly related to higher behavioral accuracy in letter-speech sound coupling. On a more general level, the timing of the earlier mismatch negativity (MMN) in the simultaneous condition (AV0) measured at T1, significantly related to reading fluency at both T1 and T2 as well as with reading gains. Our findings suggest that the reduced neural integration of letters and speech sounds in dyslexic children may show moderate improvement with reading instruction and training and that behavioral improvements relate especially to individual differences in the timing of this neural integration.

  18. Crossmodal deficit in dyslexic children: practice affects the neural timing of letter-speech sound integration

    Directory of Open Access Journals (Sweden)

    Gojko eŽarić

    2015-06-01

    Full Text Available A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills remains unknown. In this research, we examined changes in event-related potential (ERP measures of letter-speech sound integration over a 6-month period during which 9-year-old dyslexic readers (n=17 followed a training in letter-speech sound coupling next to their regular reading curriculum. We presented the Dutch spoken vowels /a/ and /o/ as standard and deviant stimuli in one auditory and two audiovisual oddball conditions. In one audiovisual condition (AV0, the letter ‘a’ was presented simultaneously with the vowels, while in the other (AV200 it was preceding vowel onset for 200 ms. Prior to the training (T1, dyslexic readers showed the expected pattern of typical auditory mismatch responses, together with the absence of letter-speech sound effects in a late negativity (LN window. After the training (T2, our results showed earlier (and enhanced crossmodal effects in the LN window. Most interestingly, earlier LN latency at T2 was significantly related to higher behavioral accuracy in letter-speech sound coupling. On a more general level, the timing of the earlier mismatch negativity (MMN in the simultaneous condition (AV0 measured at T1, significantly related to reading fluency at both T1 and T2 as well as with reading gains. Our findings suggest that the reduced neural integration of letters and speech sounds in dyslexic children may show moderate improvement with reading instruction and training and that behavioral improvements relate especially to individual differences in the timing of this neural integration.

  19. A Novel Classification Approach through Integration of Rough Sets and Back-Propagation Neural Network

    Directory of Open Access Journals (Sweden)

    Lei Si

    2014-01-01

    Full Text Available Classification is an important theme in data mining. Rough sets and neural networks are the most common techniques applied in data mining problems. In order to extract useful knowledge and classify ambiguous patterns effectively, this paper presented a hybrid algorithm based on the integration of rough sets and BP neural network to construct a novel classification system. The attribution values were discretized through PSO algorithm firstly to establish a decision table. The attribution reduction algorithm and rules extraction method based on rough sets were proposed, and the flowchart of proposed approach was designed. Finally, a prototype system was developed and some simulation examples were carried out. Simulation results indicated that the proposed approach was feasible and accurate and was outperforming others.

  20. Integrating genetic algorithm method with neural network for land use classification using SZ-3 CMODIS data

    Institute of Scientific and Technical Information of China (English)

    WANG Changyao; LUO Chengfeng; LIU Zhengjun

    2005-01-01

    This paper presents a methodology on land use mapping using CMODIS (Chinese Moderate Resolution Imaging Spectroradiometer ) data on-board SZ-3 (Shenzhou 3) spacecraft. The integrated method is composed of genetic algorithm (GA) for feature extraction and neural network classifier for land use classification. In the data preprocessing, a moment matching method was adopted to reuse classification was obtained. To generate a land use map, the three layers back propagation neural network classifier is used for training the samples and classification. Compared with the Maximum Likelihood classification algorithm, the results show that the accuracy of land use classification is obviously improved by using our proposed method, the selected band number in the classification process is reduced,and the computational performance for training and classification is improved. The result also shows that the CMODIS data can be effectively used for land use/land cover classification and change monitoring at regional and global scale.

  1. CMOS On-Chip Optoelectronic Neural Interface Device with Integrated Light Source for Optogenetics

    Science.gov (United States)

    Sawadsaringkarn, Y.; Kimura, H.; Maezawa, Y.; Nakajima, A.; Kobayashi, T.; Sasagawa, K.; Noda, T.; Tokuda, T.; Ohta, J.

    2012-03-01

    A novel optoelectronic neural interface device is proposed for target applications in optogenetics for neural science. The device consists of a light emitting diode (LED) array implemented on a CMOS image sensor for on-chip local light stimulation. In this study, we designed a suitable CMOS image sensor equipped with on-chip electrodes to drive the LEDs, and developed a device structure and packaging process for LED integration. The prototype device produced an illumination intensity of approximately 1 mW with a driving current of 2.0 mA, which is expected to be sufficient to activate channelrhodopsin (ChR2). We also demonstrated the functions of light stimulation and on-chip imaging using a brain slice from a mouse as a target sample.

  2. A low-power 32-channel digitally programmable neural recording integrated circuit.

    Science.gov (United States)

    Wattanapanitch, W; Sarpeshkar, R

    2011-12-01

    We report the design of an ultra-low-power 32-channel neural-recording integrated circuit (chip) in a 0.18 μ m CMOS technology. The chip consists of eight neural recording modules where each module contains four neural amplifiers, an analog multiplexer, an A/D converter, and a serial programming interface. Each amplifier can be programmed to record either spikes or LFPs with a programmable gain from 49-66 dB. To minimize the total power consumption, an adaptive-biasing scheme is utilized to adjust each amplifier's input-referred noise to suit the background noise at the recording site. The amplifier's input-referred noise can be adjusted from 11.2 μVrms (total power of 5.4 μW) down to 5.4 μVrms (total power of 20 μW) in the spike-recording setting. The ADC in each recording module digitizes the a.c. signal input to each amplifier at 8-bit precision with a sampling rate of 31.25 kS/s per channel, with an average power consumption of 483 nW per channel, and, because of a.c. coupling, allows d.c. operation over a wide dynamic range. It achieves an ENOB of 7.65, resulting in a net efficiency of 77 fJ/State, making it one of the most energy-efficient designs for neural recording applications. The presented chip was successfully tested in an in vivo wireless recording experiment from a behaving primate with an average power dissipation per channel of 10.1 μ W. The neural amplifier and the ADC occupy areas of 0.03 mm(2) and 0.02 mm(2) respectively, making our design simultaneously area efficient and power efficient, thus enabling scaling to high channel-count systems.

  3. Technology-Driven and Evidence-Based Genomic Analysis for Integrated Pediatric and Prenatal Genetics Evaluation

    Institute of Scientific and Technical Information of China (English)

    Yuan Wei; Fang Xu; Peining Li

    2013-01-01

    The first decade since the completion of the Human Genome Project has been marked with rapid development of genomic technologies and their immediate clinical applications.Genomic analysis using oligonucleotide array comparative genomic hybridization (aCGH) or single nucleotide polymorphism (SNP) chips has been applied to pediatric patients with developmental and intellectual disabilities (DD/ID),multiple congenital anomalies (MCA) and autistic spectrum disorders (ASD).Evaluation of analytical and clinical validities of aCGH showed > 99% sensitivity and specificity and increased analytical resolution by higher density probe coverage.Reviews of case series,multi-center comparison and large patient-control studies demonstrated a diagnostic yield of 12%-20%; approximately 60% of these abnormalities were recurrent genomic disorders.This pediatric experience has been extended toward prenatal diagnosis.A series of reports indicated approximately 10% of pregnancies with ultrasound-detected structural anomalies and normal cytogenetic findings had genomic abnormalities,and 30% of these abnormalities were syndromic genomic disorders.Evidence-based practice guidelines and standards for implementing genomic analysis and web-delivered knowledge resources for interpreting genomic findings have been established.The progress from this technology-driven and evidence-based genomic analysis provides not only opportunities to dissect disease-causing mechanisms and develop rational therapeutic interventions but also important lessons for integrating genomic sequencing into pediatric and prenatal genetic evaluation.

  4. VESPA: Software to Facilitate Genomic Annotation of Prokaryotic Organisms Through Integration of Proteomic and Transcriptomic Data

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Elena S.; McCue, Lee Ann; Rutledge, Alexandra C.; Jensen, Jeffrey L.; Walker, Julia; Kobold, Mark A.; Webb, Samantha R.; Payne, Samuel H.; Ansong, Charles; Adkins, Joshua N.; Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2012-04-25

    Visual Exploration and Statistics to Promote Annotation (VESPA) is an interactive visual analysis software tool that facilitates the discovery of structural mis-annotations in prokaryotic genomes. VESPA integrates high-throughput peptide-centric proteomics data and oligo-centric or RNA-Seq transcriptomics data into a genomic context. The data may be interrogated via visual analysis across multiple levels of genomic resolution, linked searches, exports and interaction with BLAST to rapidly identify location of interest within the genome and evaluate potential mis-annotations.

  5. Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors.

    Science.gov (United States)

    Wu, Yun; Xu, Kun; Ren, Chonghua; Li, Xinyi; Lv, Huijiao; Han, Furong; Wei, Zehui; Wang, Xin; Zhang, Zhiying

    2017-03-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has recently emerged as a simple, yet powerful genome engineering tool, which has been widely used for genome modification in various organisms and cell types. However, screening biallelic genome-modified cells is often time-consuming and technically challenging. In this study, we incorporated two different surrogate reporter cassettes into paired donor plasmids, which were used as both the surrogate reporters and the knock-in donors. By applying our dual surrogate reporter-integrated donor system, we demonstrate high frequency of CRISPR/Cas9-mediated biallelic genome integration in both human HEK293T and porcine PK15 cells (34.09% and 18.18%, respectively). Our work provides a powerful genetic tool for assisting the selection and enrichment of cells with targeted biallelic genome modification. © 2017 Federation of European Biochemical Societies.

  6. The study of neural tube defects after the Human Genome Project and folic acid fortification of foods.

    Science.gov (United States)

    Graf, W D; Oleinik, O E

    2000-12-01

    The implementation of folic acid fortification will eliminate a proportion of neural tube defects (NTD). As a result, the etiologic and clinical profiles of the developmental disorder may both change. In the assessment of NTD as it evolves, the bioinformatics structure and content of the Human Genome Project will find vital application. One important development will be an enhanced understanding of the role of folic acid in global regulation of gene expression through epigenetic processes. In addition, bioinformatics will facilitate coordination of research in the basic sciences with clinical investigations to better define remaining etiologic factors.

  7. Neural Integration Underlying a Time-Compensated Sun Compass in the Migratory Monarch Butterfly

    Directory of Open Access Journals (Sweden)

    Eli Shlizerman

    2016-04-01

    Full Text Available Migrating eastern North American monarch butterflies use a time-compensated sun compass to adjust their flight to the southwest direction. Although the antennal genetic circadian clock and the azimuth of the sun are instrumental for proper function of the compass, it is unclear how these signals are represented on a neuronal level and how they are integrated to produce flight control. To address these questions, we constructed a receptive field model of the compound eye that encodes the solar azimuth. We then derived a neural circuit model that integrates azimuthal and circadian signals to correct flight direction. The model demonstrates an integration mechanism, which produces robust trajectories reaching the southwest regardless of the time of day and includes a configuration for remigration. Comparison of model simulations with flight trajectories of butterflies in a flight simulator shows analogous behaviors and affirms the prediction that midday is the optimal time for migratory flight.

  8. A microsystem integration platform dedicated to build multi-chip-neural interfaces.

    Science.gov (United States)

    Ayoub, Amer E; Gosselin, Benoit; Sawan, Mohamad

    2007-01-01

    In this paper, we present an electrical discharge machining (EDM) technique associated with electrochemical steps to construct an appropriate biological interface to neural tissues. The presented microprobe design permits to short the time of production compared to available techniques, while improving the integrity of the electrodes. In addition, we are using a 3D approach to create compact and independent microsystem integration platefrom incorporating array of electrodes and signal processing chips. System-in-package and die-stacking are used to connect the integrated circuits and the array of electrodes on the platform. This approach enables to build a device that will fit in a volume smaller than 1.7 x 1.7 x 3.0 mm(3). This demonstrates the possibility of creating small devices that are suitable to fit in restricted areas for interfacing the brain.

  9. INDIGO - INtegrated data warehouse of microbial genomes with examples from the red sea extremophiles.

    Science.gov (United States)

    Alam, Intikhab; Antunes, André; Kamau, Allan Anthony; Ba Alawi, Wail; Kalkatawi, Manal; Stingl, Ulrich; Bajic, Vladimir B

    2013-01-01

    The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.

  10. INDIGO - INtegrated data warehouse of microbial genomes with examples from the red sea extremophiles.

    Directory of Open Access Journals (Sweden)

    Intikhab Alam

    Full Text Available BACKGROUND: The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. RESULTS: We developed a data warehouse system (INDIGO that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. CONCLUSIONS: We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.

  11. iPiG: integrating peptide spectrum matches into genome browser visualizations.

    Directory of Open Access Journals (Sweden)

    Mathias Kuhring

    Full Text Available Proteogenomic approaches have gained increasing popularity, however it is still difficult to integrate mass spectrometry identifications with genomic data due to differing data formats. To address this difficulty, we introduce iPiG as a tool for the integration of peptide identifications from mass spectrometry experiments into existing genome browser visualizations. Thereby, the concurrent analysis of proteomic and genomic data is simplified and proteomic results can directly be compared to genomic data. iPiG is freely available from https://sourceforge.net/projects/ipig/. It is implemented in Java and can be run as a stand-alone tool with a graphical user-interface or integrated into existing workflows. Supplementary data are available at PLOS ONE online.

  12. An integrated encyclopedia of DNA elements in the human genome.

    Science.gov (United States)

    2012-09-01

    The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

  13. Neural-activity mapping of memory-based dominance in the crow: neural networks integrating individual discrimination and social behaviour control.

    Science.gov (United States)

    Nishizawa, K; Izawa, E-I; Watanabe, S

    2011-12-01

    Large-billed crows (Corvus macrorhynchos), highly social birds, form stable dominance relationships based on the memory of win/loss outcomes of first encounters and on individual discrimination. This socio-cognitive behaviour predicts the existence of neural mechanisms for integration of social behaviour control and individual discrimination. This study aimed to elucidate the neural substrates of memory-based dominance in crows. First, the formation of dominance relationships was confirmed between males in a dyadic encounter paradigm. Next, we examined whether neural activities in 22 focal nuclei of pallium and subpallium were correlated with social behaviour and stimulus familiarity after exposure to dominant/subordinate familiar individuals and unfamiliar conspecifics. Neural activity was determined by measuring expression level of the immediate-early-gene (IEG) protein Zenk. Crows displayed aggressive and/or submissive behaviour to opponents less frequently but more discriminatively in subsequent encounters, suggesting stable dominance based on memory, including win/loss outcomes of the first encounters and individual discrimination. Neural correlates of aggressive and submissive behaviour were found in limbic subpallium including septum, bed nucleus of the striae terminalis (BST), and nucleus taeniae of amygdala (TnA), but also those to familiarity factor in BST and TnA. Contrastingly, correlates of social behaviour were little in pallium and those of familiarity with exposed individuals were identified in hippocampus, medial meso-/nidopallium, and ventro-caudal nidopallium. Given the anatomical connection and neural response patterns of the focal nuclei, neural networks connecting pallium and limbic subpallium via hippocampus could be involved in the integration of individual discrimination and social behaviour control in memory-based dominance in the crow.

  14. Identification of genes required for neural-specific glycosylation using functional genomics.

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino

    Full Text Available Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating α1,3-fucosylation. Further analyses revealed that an RNA-binding protein, second mitotic wave missing (Swm, upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells.

  15. Human neural progenitors derived from integration-free iPSCs for SCI therapy

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2017-03-01

    Full Text Available As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs provide great capability for tissue regeneration, particularly in spinal cord injury (SCI. However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

  16. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Sung, Wing-Kin; Zheng, Hancheng; Li, Shuyu;

    2012-01-01

    To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) tha...

  17. Integrated genome-based studies of Shewanella ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Segre Daniel; Beg Qasim

    2012-02-14

    This project was a component of the Shewanella Federation and, as such, contributed to the overall goal of applying the genomic tools to better understand eco-physiology and speciation of respiratory-versatile members of Shewanella genus. Our role at Boston University was to perform bioreactor and high throughput gene expression microarrays, and combine dynamic flux balance modeling with experimentally obtained transcriptional and gene expression datasets from different growth conditions. In the first part of project, we designed the S. oneidensis microarray probes for Affymetrix Inc. (based in California), then we identified the pathways of carbon utilization in the metal-reducing marine bacterium Shewanella oneidensis MR-1, using our newly designed high-density oligonucleotide Affymetrix microarray on Shewanella cells grown with various carbon sources. Next, using a combination of experimental and computational approaches, we built algorithm and methods to integrate the transcriptional and metabolic regulatory networks of S. oneidensis. Specifically, we combined mRNA microarray and metabolite measurements with statistical inference and dynamic flux balance analysis (dFBA) to study the transcriptional response of S. oneidensis MR-1 as it passes through exponential, stationary, and transition phases. By measuring time-dependent mRNA expression levels during batch growth of S. oneidensis MR-1 under two radically different nutrient compositions (minimal lactate and nutritionally rich LB medium), we obtain detailed snapshots of the regulatory strategies used by this bacterium to cope with gradually changing nutrient availability. In addition to traditional clustering, which provides a first indication of major regulatory trends and transcription factors activities, we developed and implemented a new computational approach for Dynamic Detection of Transcriptional Triggers (D2T2). This new method allows us to infer a putative topology of transcriptional dependencies

  18. Exonuclease 1 is essential for maintaining genomic stability and the proliferative capacity of neural but not hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Junling Zhang

    2014-01-01

    Full Text Available Exonuclease 1 (Exo1 has been implicated in the regulation of DNA damage responses in stem cells with dysfunctional telomeres. However, it is unclear whether Exo1-mediated DNA maintenance pathways play a role in the maintenance of genomic stability and the self-renewal of tissue stem cells in mice with functional telomeres. Here, we analyzed the proliferative capacity of neural stem cells (NSCs and hematopoietic stem cells (HSCs from Exo1−/− mice. Our study shows that Exo1 deficiency impairs the maintenance of genomic stability and proliferative capacity in NSCs but not HSCs. In line with these results, we detected a decrease in proliferation and an up-regulation of p21 expression levels in Exo1-deficient NSCs but not Exo1-deficient HSCs. Our data provide experimental evidence that Exo1 deficiency has a differential impact on the homeostasis and proliferative capacity of tissue stem cells in the brain and bone marrow, suggesting that different tissue stem cells utilize distinct mechanisms for maintaining their genomic stability. Our current study provides important insight into the role of Exo1-mediated DNA maintenance pathways in the maintenance of genomic stability and the proliferative capacity of tissue stem cells.

  19. Integrated genomics of Mucorales reveals novel therapeutic targets

    Science.gov (United States)

    Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

  20. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    TIEDJE, JAMES M; KONSTANTINIDIS, KOSTAS; WORDEN, MARK

    2014-01-08

    The aim of the work reported is to study Shewanella population genomics, and to understand the evolution, ecophysiology, and speciation of Shewanella. The tasks supporting this aim are: to study genetic and ecophysiological bases defining the core and diversification of Shewanella species; to determine gene content patterns along redox gradients; and to Investigate the evolutionary processes, patterns and mechanisms of Shewanella.

  1. Resolution of sensory ambiguities for gaze stabilization requires a second neural integrator

    Science.gov (United States)

    Green, Andrea M.; Angelaki, Dora E.

    2003-01-01

    The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

  2. Parietofrontal integrity determines neural modulation associated with grasping imagery after stroke

    Science.gov (United States)

    Modir Shanechi, Amirali; Fourkas, Alissa D.; Weber, Cornelia; Birbaumer, Niels

    2012-01-01

    Chronic stroke patients with heterogeneous lesions, but no direct damage to the primary sensorimotor cortex, are capable of longitudinally acquiring the ability to modulate sensorimotor rhythms using grasping imagery of the affected hand. Volitional modulation of neural activity can be used to drive grasping functions of the paralyzed hand through a brain–computer interface. The neural substrates underlying this skill are not known. Here, we investigated the impact of individual patient's lesion pathology on functional and structural network integrity related to this volitional skill. Magnetoencephalography data acquired throughout training was used to derive functional networks. Structural network models and local estimates of extralesional white matter microstructure were constructed using T1-weighted and diffusion-weighted magnetic resonance imaging data. We employed a graph theoretical approach to characterize emergent properties of distributed interactions between nodal brain regions of these networks. We report that interindividual variability in patients’ lesions led to differential impairment of functional and structural network characteristics related to successful post-training sensorimotor rhythm modulation skill. Patients displaying greater magnetoencephalography global cost-efficiency, a measure of information integration within the distributed functional network, achieved greater levels of skill. Analysis of lesion damage to structural network connectivity revealed that the impact on nodal betweenness centrality of the ipsilesional primary motor cortex, a measure that characterizes the importance of a brain region for integrating visuomotor information between frontal and parietal cortical regions and related thalamic nuclei, correlated with skill. Edge betweenness centrality, an analogous measure, which assesses the role of specific white matter fibre pathways in network integration, showed a similar relationship between skill and a portion of

  3. The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse.

    Science.gov (United States)

    Blake, Judith A; Bult, Carol J; Eppig, Janan T; Kadin, James A; Richardson, Joel E

    2014-01-01

    The Mouse Genome Database (MGD) (http://www.informatics.jax.org) is the community model organism database resource for the laboratory mouse, a premier animal model for the study of genetic and genomic systems relevant to human biology and disease. MGD maintains a comprehensive catalog of genes, functional RNAs and other genome features as well as heritable phenotypes and quantitative trait loci. The genome feature catalog is generated by the integration of computational and manual genome annotations generated by NCBI, Ensembl and Vega/HAVANA. MGD curates and maintains the comprehensive listing of functional annotations for mouse genes using the Gene Ontology, and MGD curates and integrates comprehensive phenotype annotations including associations of mouse models with human diseases. Recent improvements include integration of the latest mouse genome build (GRCm38), improved access to comparative and functional annotations for mouse genes with expanded representation of comparative vertebrate genomes and new loads of phenotype data from high-throughput phenotyping projects. All MGD resources are freely available to the research community.

  4. Integrating cytogenetics and genomics in comparative evolutionary studies of cichlid fish

    Directory of Open Access Journals (Sweden)

    Mazzuchelli Juliana

    2012-09-01

    Full Text Available Abstract Background The availability of a large number of recently sequenced vertebrate genomes opens new avenues to integrate cytogenetics and genomics in comparative and evolutionary studies. Cytogenetic mapping can offer alternative means to identify conserved synteny shared by distinct genomes and also to define genome regions that are still not fine characterized even after wide-ranging nucleotide sequence efforts. An efficient way to perform comparative cytogenetic mapping is based on BAC clones mapping by fluorescence in situ hybridization. In this report, to address the knowledge gap on the genome evolution in cichlid fishes, BAC clones of an Oreochromis niloticus library covering the linkage groups (LG 1, 3, 5, and 7 were mapped onto the chromosomes of 9 African cichlid species. The cytogenetic mapping data were also integrated with BAC-end sequences information of O. niloticus and comparatively analyzed against the genome of other fish species and vertebrates. Results The location of BACs from LG1, 3, 5, and 7 revealed a strong chromosomal conservation among the analyzed cichlid species genomes, which evidenced a synteny of the markers of each LG. Comparative in silico analysis also identified large genomic blocks that were conserved in distantly related fish groups and also in other vertebrates. Conclusions Although it has been suggested that fishes contain plastic genomes with high rates of chromosomal rearrangements and probably low rates of synteny conservation, our results evidence that large syntenic chromosome segments have been maintained conserved during evolution, at least for the considered markers. Additionally, our current cytogenetic mapping efforts integrated with genomic approaches conduct to a new perspective to address important questions involving chromosome evolution in fishes.

  5. A Regulatory Role for RUNX1, RUNX3 in the Maintenance of Genomic Integrity.

    Science.gov (United States)

    Krishnan, Vaidehi; Ito, Yoshiaki

    2017-01-01

    All human cells are constantly attacked by endogenous and exogenous agents that damage the integrity of their genomes. Yet, the ensuing damage is mostly fixed and very rarely gives rise to genomic defects that promote cancer formation. This is due to the co-ordinated functioning of DNA repair proteins and checkpoint mechanisms that accurately detect and repair DNA damage to ensure genomic fitness. According to accumulating evidence, the RUNX family of transcription factors participate in the maintenance of genomic stability through transcriptional and non-transcriptional mechanisms. RUNX1 and RUNX3 maintain genomic integrity in a transcriptional manner by regulating the transactivation of apoptotic genes following DNA damage via complex formation with p53. RUNX1 and RUNX3 also maintain genomic integrity in a non-transcriptional manner during interstand crosslink repair by promoting the recruitment of FANCD2 to sites of DNA damage. Since RUNX genes are frequently aberrant in human cancer, here, we argue that one of the major modes by which RUNX inactivation promotes neoplastic transformation is through the loss of genomic integrity. In particular, there exists strong evidence that leukemic RUNX1-fusions such as RUNX1-ETO disrupt genomic integrity and induce a "mutator" phenotype during the early stages of leukemogenesis. Consistent with increased DNA damage accumulation induced by RUNX1-ETO, PARP inhibition has been shown to be an effective synthetic-lethal therapeutic approach against RUNX1-ETO expressing leukemias. Here, in this chapter we will examine current evidence suggesting that the tumor suppressor potential of RUNX proteins can be at least partly attributed to their ability to ensure high-fidelity DNA repair and thus prevent mutational accumulation during cancer progression.

  6. Integrated genomic analysis of survival outliers in glioblastoma.

    Science.gov (United States)

    Peng, Sen; Dhruv, Harshil; Armstrong, Brock; Salhia, Bodour; Legendre, Christophe; Kiefer, Jeffrey; Parks, Julianna; Virk, Selene; Sloan, Andrew E; Ostrom, Quinn T; Barnholtz-Sloan, Jill S; Tran, Nhan L; Berens, Michael E

    2017-06-01

    To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients. LTS GB showed frequent chromosomal gains in 4q12 (platelet derived growth factor receptor alpha and KIT) and 12q14.1 (cyclin-dependent kinase 4), and deletion in 19q13.33 (BAX, branched chain amino-acid transaminase 2, and cluster of differentiation 33). STS GB showed frequent deletion in 9p11.2 (forkhead box D4-like 2 and aquaporin 7 pseudogene 3) and 22q11.21 (Hypermethylated In Cancer 2). LTS GB showed 2-fold more frequent copy number deletions compared with STS GB. Gene expression differences showed the STS cohort with altered transcriptional regulators: activation of signal transducer and activator of transcription (STAT)5a/b, nuclear factor-kappaB (NF-κB), and interferon-gamma (IFNG), and inhibition of mitogen-activated protein kinase (MAPK1), extracellular signal-regulated kinase (ERK)1/2, and estrogen receptor (ESR)1. Expression-based biological concepts prominent in the STS cohort include metabolic processes, anaphase-promoting complex degradation, and immune processes associated with major histocompatibility complex class I antigen presentation; the LTS cohort features genes related to development, morphogenesis, and the mammalian target of rapamycin signaling pathway. Whole genome methylation analyses showed that a methylation signature of 89 probes distinctly separates LTS from STS GB tumors. We posit that genomic instability is associated with longer survival of GB (possibly with vulnerability to standard therapy); conversely, genomic

  7. Role of the hippocampus in memory formation: restorative encoding memory integration neural device as a cognitive neural prosthesis.

    Science.gov (United States)

    Berger, Theodore; Song, Dong; Chan, Rosa; Shin, Dae; Marmarelis, Vasilis; Hampson, Robert; Sweatt, Andrew; Heck, Christi; Liu, Charles; Wills, Jack; Lacoss, Jeff; Granacki, John; Gerhardt, Greg; Deadwyler, Sam

    2012-01-01

    Remind, which stands for "restorative encoding memory integration neural device," is a Defense Advanced Research Projects Agency (DARPA)-sponsored program to construct the first-ever cognitive prosthesis to replace lost memory function and enhance the existing memory capacity in animals and, ultimately, in humans. Reaching this goal involves understanding something fundamental about the brain that has not been understood previously: how the brain internally codes memories. In developing a hippocampal prosthesis for the rat, we have been able to demonstrate a multiple-input, multiple- output (MIMO) nonlinear model that predicts in real time the spatiotemporal codes for specific memories required for correct performance on a standard learning/memory task, i.e., delayed-nonmatch-to-sample (DNMS) memory. The MIMO model has been tested successfully in a number of contexts; most notably, in animals with a pharmacologically disabled hippocampus, we were able to reinstate long-term memories necessary for correct DNMS behavior by substituting a MIMO model-predicted code, delivered by electrical stimulation to the hippocampus through an array of electrodes, resulting in spatiotemporal hippocampal activity that is normally generated endogenously. We also have shown that delivering the same model-predicted code to electrode-implanted control animals with a normally functioning hippocampus substantially enhances animals memory capacity above control levels. These results in rodents have formed the basis for extending the MIMO model to nonhuman primates; this is now underway as the last step of the REMIND program before developing a MIMO-based cognitive prosthesis for humans.

  8. Small tumor virus genomes are integrated near nuclear matrix attachment regions in transformed cells.

    Science.gov (United States)

    Shera, K A; Shera, C A; McDougall, J K

    2001-12-01

    More than 15% of human cancers have a viral etiology. In benign lesions induced by the small DNA tumor viruses, viral genomes are typically maintained extrachromosomally. Malignant progression is often associated with viral integration into host cell chromatin. To study the role of viral integration in tumorigenesis, we analyzed the positions of integrated viral genomes in tumors and tumor cell lines induced by the small oncogenic viruses, including the high-risk human papillomaviruses, hepatitis B virus, simian virus 40, and human T-cell leukemia virus type 1. We show that viral integrations in tumor cells lie near cellular sequences identified as nuclear matrix attachment regions (MARs), while integrations in nonneoplastic cells show no significant correlation with these regions. In mammalian cells, the nuclear matrix functions in gene expression and DNA replication. MARs play varied but poorly understood roles in eukaryotic gene expression. Our results suggest that integrated tumor virus genomes are subject to MAR-mediated transcriptional regulation, providing insight into mechanisms of viral carcinogenesis. Furthermore, the viral oncoproteins serve as invaluable tools for the study of mechanisms controlling cellular growth. Similarly, our demonstration that integrated viral genomes may be subject to MAR-mediated transcriptional effects should facilitate elucidation of fundamental mechanisms regulating eukaryotic gene expression.

  9. Integration sites of Epstein-Barr virus genome on chromosomes of human lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wuu, K.D.; Chen, Y.J.; Wang-Wuu, S. [Institute of Genetics, Taipei (Taiwan, Province of China)

    1994-09-01

    Epstein-Barr virus (EBV) is the pathogen of infectious mononucleosis. The viral genome is present in more than 95% of the African cases of Burkitt lymphoma and it is usually maintained in episomal form in the tumor cells. Viral integration has been described only for Nanalwa which is a Burkitt lymphoma cell line lacking episomes. In order to examine the role of EBV in the immortalization of human Blymphocytes, we investigated whether the EBV integration into the human genome is essential. If the integration does occur, we would like to know whether the integration is randomly distributed or whether the viral DNA integrates preferentially at certain sites. Fourteen in vitro immortalized human lymphoblastoid cell lines (LCLs) were examined by fluorescence in situ hybridization (FISH) with a biotinylated EBV BamHI w DNA fragment as probe. The episomal form of EBV DNA was found in all cells of these cell lines, while only about 65% of the cells have the integrated viral DNA. This might suggest that integration is not a pre-requisite for cell immortalization. Although all chromosomes, except Y, have been found with integrated viral genome, chromsomes 1 and 5 are the most frequent EBV DNA carrier (p<0.05). Nine chromosome bands, namely, 1p31, 1q31, 2q32, 3q13, 3q26, 5q14, 6q24, 7q31 and 12q21, are preferential targets for EBV integration (p<0.001). Eighty percent of the total 938 EBV hybridization signals were found to be at G-band-positive area. This suggests that the mechanism of EBV integration might be different from that of the retroviruses, which specifically integrate to G-band-negative areas. Thus, we conclude that the integration of EBV to host genome is non-random and it may have something to do with the structure of chromosome and DNA sequences.

  10. Genome integrity and disease prevention in the nervous system.

    Science.gov (United States)

    McKinnon, Peter J

    2017-06-15

    Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous damage underpins disease pathology. Generally, the types of causative DNA damage are associated with replication, transcription, or oxidative metabolism; other direct sources of endogenous lesions may arise from aberrant topoisomerase activity or ribonucleotide incorporation into DNA. This review focuses on the etiology of DNA damage in the nervous system and the genome stability pathways that prevent human neurologic disease. © 2017 McKinnon; Published by Cold Spring Harbor Laboratory Press.

  11. SOP for pathway inference in Integrated Microbial Genomes (IMG).

    Science.gov (United States)

    Anderson, Iain; Chen, Amy; Markowitz, Victor; Kyrpides, Nikos; Ivanova, Natalia

    2011-12-31

    One of the most important aspects of genomic analysis is the prediction of which pathways, both metabolic and non-metabolic, are present in an organism. In IMG, this is carried out by the assignment of IMG terms, which are organized into IMG pathways. Based on manual and automatic assignment of IMG terms, the presence or absence of IMG pathways is automatically inferred. The three categories of pathway assertion are asserted (likely present), not asserted (likely absent), and unknown. In the unknown category, at least one term necessary for the pathway is missing, but an ortholog in another organism has the corresponding term assigned to it. Automatic pathway inference is an important initial step in genome analysis.

  12. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  13. Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

    Science.gov (United States)

    Luan, Lan; Wei, Xiaoling; Zhao, Zhengtuo; Siegel, Jennifer J.; Potnis, Ojas; Tuppen, Catherine A; Lin, Shengqing; Kazmi, Shams; Fowler, Robert A.; Holloway, Stewart; Dunn, Andrew K.; Chitwood, Raymond A.; Xie, Chong

    2017-01-01

    Implanted brain electrodes construct the only means to electrically interface with individual neurons in vivo, but their recording efficacy and biocompatibility pose limitations on scientific and clinical applications. We showed that nanoelectronic thread (NET) electrodes with subcellular dimensions, ultraflexibility, and cellular surgical footprints form reliable, glial scar–free neural integration. We demonstrated that NET electrodes reliably detected and tracked individual units for months; their impedance, noise level, single-unit recording yield, and the signal amplitude remained stable during long-term implantation. In vivo two-photon imaging and postmortem histological analysis revealed seamless, subcellular integration of NET probes with the local cellular and vasculature networks, featuring fully recovered capillaries with an intact blood-brain barrier and complete absence of chronic neuronal degradation and glial scar.

  14. Genome maintenance and transcription integrity in ageing and disease

    Directory of Open Access Journals (Sweden)

    Stefanie eWolters

    2013-02-01

    Full Text Available DNA Damage contributes to cancer development and ageing. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated ageing (Schumacher et al., 2008. DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007. Cellular response mechanisms to stalled RNA polymerase (RNAP II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the ageing organism (Garinis et al., 2009. Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in ageing and disease. We discuss how the nucleotide excision repair (NER system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer.

  15. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    Science.gov (United States)

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  16. Advantages of Comparative Studies in Songbirds to Understand the Neural Basis of Sensorimotor Integration.

    Science.gov (United States)

    Murphy, Karagh; James, Logan S; Sakata, Jon T; Prather, Jonathan F

    2017-03-22

    Sensorimotor integration is the process through which the nervous system creates a link between motor commands and associated sensory feedback. This process allows for the acquisition and refinement of many behaviors, including learned communication behaviors like speech and birdsong. Consequently, it is important to understand fundamental mechanisms of sensorimotor integration, and comparative analyses of this process can provide vital insight. Songbirds offer a powerful comparative model system to study how the nervous system links motor and sensory information for learning and control. This is because the acquisition, maintenance, and control of birdsong critically depend on sensory feedback. Furthermore, there is an incredible diversity of song organizations across songbird species, ranging from songs with simple, stereotyped sequences to songs with complex sequencing of vocal gestures, as well as a wide diversity of song repertoire sizes. Despite this diversity, the neural circuitry for song learning, control, and maintenance remains highly similar across species. Here, we highlight the utility of songbirds for the analysis of sensorimotor integration and the insights about mechanisms of sensorimotor integration gained by comparing different songbird species. Key conclusions from this comparative analysis are that variation in song sequence complexity seems to covary with the strength of feedback signals in sensorimotor circuits, and that sensorimotor circuits contain distinct representations of elements in the vocal repertoire, possibly enabling evolutionary variation in repertoire sizes. We conclude our review by highlighting important areas of research that could benefit from increased comparative focus, with particular emphasis on the integration of new technologies.

  17. Integrating Neural Networks and Conceptual Modelling for Flood Forecasting on the Tiber River

    Science.gov (United States)

    Napolitano, G.; See, L.; Savi, F.

    2009-04-01

    The Tiber River has a catchment area of approximately 17,000 km2. The river crosses 6 regions and is about 300 km in length. This study is focused on the bottom part of the catchment, between Rome and the Corbara dam, which is located approximately 150 km north of Rome, with a reservoir active storage of 165 hm3. The area from Corbara dam (11,000 km2) can be subdivided into 37 ungauged and 3 gauged sub-basins. At the bottom of the basin is the city of Rome, which is at risk from flooding when extreme events with a return period of about 200 years occur. Both conceptual modeling and Artificial Neural Networks (ANNS) have already been applied individually to forecasting historical floods for the city of Rome. The results of both models are promising but each one has different strengths. This study considers how hybrid techniques can be applied to the integration of both conceptual and ANN models to improve their performance further. Integration of the individual models using different techniques from the field of data fusion is investigated. Models are developed to predict hourly water levels at Ripetta gauging station in Rome for a lead time of 12 and 18 hours. Model performance is assessed using a series of absolute and relative performance measures as well as a visual inspection of the hydrograph. Keywords: real-time forecasting, flooding, rainfall-runoff modelling, Artificial Neural Networks.

  18. The NeuroMedicator—a micropump integrated with silicon microprobes for drug delivery in neural research

    Science.gov (United States)

    Spieth, S.; Schumacher, A.; Kallenbach, C.; Messner, S.; Zengerle, R.

    2012-06-01

    The NeuroMedicator is a micropump integrated with application-specific silicon microprobes aimed for drug delivery in neural research with small animals. The micropump has outer dimensions of 11 × 15 × 3 mm3 and contains 16 reservoirs each having a capacity of 0.25 µL. Thereby, the reservoirs are interconnected in a pearl-chain-like manner and are connected to two 8 mm long silicon microprobes. Each microprobe has a cross-sectional area of 250 × 250 µm2 and features an integrated drug delivery channel of 50 × 50 µm2 with an outlet of 25 µm in diameter. The drug is loaded to the micropump prior to implantation. After implantation, individual 0.25 µL portions of drug can be sequentially released by short heating pulses applied to a polydimethylsiloxane (PDMS) layer containing Expancel® microspheres. Due to local, irreversible thermal expansion of the elastic composite material, the drug is displaced from the reservoirs and released through the microprobe outlet directly to the neural tissue. While implanted, leakage of drug by diffusion occurs due to the open microprobe outlets. The maximum leakage within the first three days after implantation is calculated to be equivalent to 0.06 µL of drug solution.

  19. An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications

    Science.gov (United States)

    Wu, Fan; Stark, Eran; Im, Maesoon; Cho, Il-Joo; Yoon, Eui-Sung; Buzsáki, György; Wise, Kensall D.; Yoon, Euisik

    2013-10-01

    Objective. Optogenetics promises exciting neuroscience research by offering optical stimulation of neurons with unprecedented temporal resolution, cell-type specificity and the ability to excite as well as to silence neurons. This work provides the technical solution to deliver light to local neurons and record neural potentials, facilitating local circuit analysis and bridging the gap between optogenetics and neurophysiology research. Approach. We have designed and obtained the first in vivo validation of a neural probe with monolithically integrated electrodes and waveguide. High spatial precision enables optical excitation of targeted neurons with minimal power and recording of single-units in dense cortical and subcortical regions. Main results. The total coupling and transmission loss through the dielectric waveguide at 473 nm was 10.5 ± 1.9 dB, corresponding to an average output intensity of 9400 mW mm-2 when coupled to a 7 mW optical fiber. Spontaneous field potentials and spiking activities of multiple Channelrhodopsin-2 expressing neurons were recorded in the hippocampus CA1 region of an anesthetized rat. Blue light stimulation at intensity of 51 mW mm-2 induced robust spiking activities in the physiologically identified local populations. Significance. This minimally invasive, complete monolithic integration provides unmatched spatial precision and scalability for future optogenetics studies at deep brain regions with high neuronal density.

  20. Physical and perceptual factors shape the neural mechanisms that integrate audiovisual signals in speech comprehension.

    Science.gov (United States)

    Lee, HweeLing; Noppeney, Uta

    2011-08-01

    Face-to-face communication challenges the human brain to integrate information from auditory and visual senses with linguistic representations. Yet the role of bottom-up physical (spectrotemporal structure) input and top-down linguistic constraints in shaping the neural mechanisms specialized for integrating audiovisual speech signals are currently unknown. Participants were presented with speech and sinewave speech analogs in visual, auditory, and audiovisual modalities. Before the fMRI study, they were trained to perceive physically identical sinewave speech analogs as speech (SWS-S) or nonspeech (SWS-N). Comparing audiovisual integration (interactions) of speech, SWS-S, and SWS-N revealed a posterior-anterior processing gradient within the left superior temporal sulcus/gyrus (STS/STG): Bilateral posterior STS/STG integrated audiovisual inputs regardless of spectrotemporal structure or speech percept; in left mid-STS, the integration profile was primarily determined by the spectrotemporal structure of the signals; more anterior STS regions discarded spectrotemporal structure and integrated audiovisual signals constrained by stimulus intelligibility and the availability of linguistic representations. In addition to this "ventral" processing stream, a "dorsal" circuitry encompassing posterior STS/STG and left inferior frontal gyrus differentially integrated audiovisual speech and SWS signals. Indeed, dynamic causal modeling and Bayesian model comparison provided strong evidence for a parallel processing structure encompassing a ventral and a dorsal stream with speech intelligibility training enhancing the connectivity between posterior and anterior STS/STG. In conclusion, audiovisual speech comprehension emerges in an interactive process with the integration of auditory and visual signals being progressively constrained by stimulus intelligibility along the STS and spectrotemporal structure in a dorsal fronto-temporal circuitry.

  1. Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish

    Directory of Open Access Journals (Sweden)

    Atsuo Kawahara

    2016-05-01

    Full Text Available The zebrafish (Danio rerio is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR associated protein 9 (Cas9 system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

  2. Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish.

    Science.gov (United States)

    Kawahara, Atsuo; Hisano, Yu; Ota, Satoshi; Taimatsu, Kiyohito

    2016-05-13

    The zebrafish (Danio rerio) is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs) at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

  3. An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

    Science.gov (United States)

    Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

    2016-08-09

    Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance

  4. Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity

    OpenAIRE

    2013-01-01

    Malaria parasites replicate asexually within their mammalian hosts as haploid cells and are subject to DNA damage from the immune response and chemotherapeutic agents that can significantly disrupt genomic integrity. Examination of the annotated genome of the parasite Plasmodium falciparum identified genes encoding core proteins required for the homologous recombination (HR) pathway for repairing DNA double-strand breaks (DSBs), but surprisingly none of the components of the canonical non-hom...

  5. Figure 2 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

    Science.gov (United States)

    Grouping and sorting genomic data in IGV. The IGV user interface displaying 202 glioblastoma samples from TCGA. Samples are grouped by tumor subtype (second annotation column) and data type (first annotation column) and sorted by copy number of the EGFR locus (middle column). Adapted from Figure 1; Robinson et al. 2011

  6. Figure 4 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

    Science.gov (United States)

    Gene-list view of genomic data. The gene-list view allows users to compare data across a set of loci. The data in this figure includes copy number, mutation, and clinical data from 202 glioblastoma samples from TCGA. Adapted from Figure 7; Thorvaldsdottir H et al. 2012

  7. Figure 5 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

    Science.gov (United States)

    Split-Screen View. The split-screen view is useful for exploring relationships of genomic features that are independent of chromosomal location. Color is used here to indicate mate pairs that map to different chromosomes, chromosomes 1 and 6, suggesting a translocation event. Adapted from Figure 8; Thorvaldsdottir H et al. 2012

  8. Roles of Werner syndrome protein in protection of genome integrity

    DEFF Research Database (Denmark)

    Rossi, Marie L; Ghosh, Avik K; Bohr, Vilhelm A

    2010-01-01

    Werner syndrome protein (WRN) is one of a family of five human RecQ helicases implicated in the maintenance of genome stability. The conserved RecQ family also includes RecQ1, Bloom syndrome protein (BLM), RecQ4, and RecQ5 in humans, as well as Sgs1 in Saccharomyces cerevisiae, Rqh1...... syndrome (WS). WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance. Studies both in vitro and in vivo indicate that the roles of WRN in a variety of DNA processes are mediated by post...

  9. From integrative genomics to systems genetics in the rat to link genotypes to phenotypes

    Science.gov (United States)

    Moreno-Moral, Aida

    2016-01-01

    ABSTRACT Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emerged as powerful strategies to decipher the key genetic drivers of molecular pathways that underlie disease. Broadly speaking, integrative genomics aims to link cellular-level traits (such as mRNA expression) to the genome to identify their genetic determinants. With the characterization of several cellular-level traits within the same system, the integrative genomics approach evolved into a more comprehensive study design, called systems genetics, which aims to unravel the complex biological networks and pathways involved in disease, and in turn map their genetic control points. The first fully integrated systems genetics study was carried out in rats, and the results, which revealed conserved trans-acting genetic regulation of a pro-inflammatory network relevant to type 1 diabetes, were translated to humans. Many studies using different organisms subsequently stemmed from this example. The aim of this Review is to describe the most recent advances in the fields of integrative genomics and systems genetics applied in the rat, with a focus on studies of complex diseases ranging from inflammatory to cardiometabolic disorders. We aim to provide the genetics community with a comprehensive insight into how the systems genetics approach came to life, starting from the first integrative genomics strategies [such as expression quantitative trait loci (eQTLs) mapping] and concluding with the most sophisticated gene network-based analyses in multiple systems and disease states. Although not limited to studies that have been directly translated to humans, we will focus particularly on the successful investigations in the rat that have led to primary discoveries of genes and pathways relevant to human disease. PMID:27736746

  10. Neurogenomics: An opportunity to integrate neuroscience, genomics and bioinformatics research in Africa

    Directory of Open Access Journals (Sweden)

    Thomas K. Karikari

    2015-06-01

    Full Text Available Modern genomic approaches have made enormous contributions to improving our understanding of the function, development and evolution of the nervous system, and the diversity within and between species. However, most of these research advances have been recorded in countries with advanced scientific resources and funding support systems. On the contrary, little is known about, for example, the possible interplay between different genes, non-coding elements and environmental factors in modulating neurological diseases among populations in low-income countries, including many African countries. The unique ancestry of African populations suggests that improved inclusion of these populations in neuroscience-related genomic studies would significantly help to identify novel factors that might shape the future of neuroscience research and neurological healthcare. This perspective is strongly supported by the recent identification that diseased individuals and their kindred from specific sub-Saharan African populations lack common neurological disease-associated genetic mutations. This indicates that there may be population-specific causes of neurological diseases, necessitating further investigations into the contribution of additional, presently-unknown genomic factors. Here, we discuss how the development of neurogenomics research in Africa would help to elucidate disease-related genomic variants, and also provide a good basis to develop more effective therapies. Furthermore, neurogenomics would harness African scientists' expertise in neuroscience, genomics and bioinformatics to extend our understanding of the neural basis of behaviour, development and evolution.

  11. Comparing the neural basis of monetary reward and cognitive feedback during information-integration category learning.

    Science.gov (United States)

    Daniel, Reka; Pollmann, Stefan

    2010-01-06

    The dopaminergic system is known to play a central role in reward-based learning (Schultz, 2006), yet it was also observed to be involved when only cognitive feedback is given (Aron et al., 2004). Within the domain of information-integration category learning, in which information from several stimulus dimensions has to be integrated predecisionally (Ashby and Maddox, 2005), the importance of contingent feedback is well established (Maddox et al., 2003). We examined the common neural correlates of reward anticipation and prediction error in this task. Sixteen subjects performed two parallel information-integration tasks within a single event-related functional magnetic resonance imaging session but received a monetary reward only for one of them. Similar functional areas including basal ganglia structures were activated in both task versions. In contrast, a single structure, the nucleus accumbens, showed higher activation during monetary reward anticipation compared with the anticipation of cognitive feedback in information-integration learning. Additionally, this activation was predicted by measures of intrinsic motivation in the cognitive feedback task and by measures of extrinsic motivation in the rewarded task. Our results indicate that, although all other structures implicated in category learning are not significantly affected by altering the type of reward, the nucleus accumbens responds to the positive incentive properties of an expected reward depending on the specific type of the reward.

  12. Fluorescent reporters for markerless genomic integration in Staphylococcus aureus

    Science.gov (United States)

    de Jong, Nienke W. M.; van der Horst, Thijs; van Strijp, Jos A. G.; Nijland, Reindert

    2017-01-01

    We present integration vectors for Staphylococcus aureus encoding the fluorescent reporters mAmetrine, CFP, sGFP, YFP, mCherry and mKate. The expression is driven either from the sarA-P1 promoter or from any other promoter of choice. The reporter can be inserted markerless in the chromosome of a wide range of S. aureus strains. The integration site chosen does not disrupt any open reading frame, provides good expression, and has no detectable effect on the strains physiology. As an intermediate construct, we present a set of replicating plasmids containing the same fluorescent reporters. Also in these reporter plasmids the sarA-P1 promoter can be replaced by any other promoter of interest for expression studies. Cassettes from the replication plasmids can be readily swapped with the integration vector. With these constructs it becomes possible to monitor reporters of separate fluorescent wavelengths simultaneously. PMID:28266573

  13. VESPA: software to facilitate genomic annotation of prokaryotic organisms through integration of proteomic and transcriptomic data

    Directory of Open Access Journals (Sweden)

    Peterson Elena S

    2012-04-01

    Full Text Available Abstract Background The procedural aspects of genome sequencing and assembly have become relatively inexpensive, yet the full, accurate structural annotation of these genomes remains a challenge. Next-generation sequencing transcriptomics (RNA-Seq, global microarrays, and tandem mass spectrometry (MS/MS-based proteomics have demonstrated immense value to genome curators as individual sources of information, however, integrating these data types to validate and improve structural annotation remains a major challenge. Current visual and statistical analytic tools are focused on a single data type, or existing software tools are retrofitted to analyze new data forms. We present Visual Exploration and Statistics to Promote Annotation (VESPA is a new interactive visual analysis software tool focused on assisting scientists with the annotation of prokaryotic genomes though the integration of proteomics and transcriptomics data with current genome location coordinates. Results VESPA is a desktop Java™ application that integrates high-throughput proteomics data (peptide-centric and transcriptomics (probe or RNA-Seq data into a genomic context, all of which can be visualized at three levels of genomic resolution. Data is interrogated via searches linked to the genome visualizations to find regions with high likelihood of mis-annotation. Search results are linked to exports for further validation outside of VESPA or potential coding-regions can be analyzed concurrently with the software through interaction with BLAST. VESPA is demonstrated on two use cases (Yersinia pestis Pestoides F and Synechococcus sp. PCC 7002 to demonstrate the rapid manner in which mis-annotations can be found and explored in VESPA using either proteomics data alone, or in combination with transcriptomic data. Conclusions VESPA is an interactive visual analytics tool that integrates high-throughput data into a genomic context to facilitate the discovery of structural mis

  14. Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch

    National Research Council Canada - National Science Library

    London, Sarah E; Clayton, David F

    2010-01-01

    .... Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors...

  15. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    NEALSON, KENNETH H.

    2013-10-15

    This project had as its goals the understanding of the ecophysiology of the genus Shewanella using various genomics approaches. As opposed to other programs involving Shewanella, this one branched out into the various areas in which Shewanella cells are active, and included both basic and applied studies. All of the work was, to some extent, related to the ability of the bacteria to accomplish electron exchange between the cell and solid state electron acceptors and/or electron donors, a process we call Extracellular Electron Transport, or EET. The major accomplishments related to several different areas: Basic Science Studies: 1. Genetics and genomics of nitrate reduction, resulting in elucidation of atypical nitrate reduction systems in Shewanella oneidensis (MR-1)[2]. 2. Influence of bacterial strain and growth conditions on iron reduction, showing that rates of reduction, extents of reduction, and the formation of secondary minerals were different for different strains of Shewanella [3,4,9]. 3. Comparative genomics as a tool for comparing metabolic capacities of different Shewanella strains, and for predicting growth and metabolism [6,10,15]. In these studies, collaboration with ORNL, PNNL, and 4. Basic studies of electron transport in strain MR-1, both to poised electrodes, and via conductive nanowires [12,13]. This included the first accurate measurements of electrical energy generation by a single cell during electrode growth [12], and the demonstration of electrical conductivity along the length of bacterial nanowires [13]. 5. Impact of surface charge and electron flow on cell movement, cell attachment, cell growth, and biofilm formation [7.18]. The demonstration that interaction with solid state electron acceptors resulted in increased motility [7] led to the description of a phenomenon called electrokinesis. The importance of this for biofilm formation and for electron flow was hypothesized by Nealson & Finkel [18], and is now under study in several

  16. SEMICONDUCTOR INTEGRATED CIRCUITS: Low power CMOS preamplifier for neural recording applications

    Science.gov (United States)

    Xu, Zhang; Weihua, Pei; Beiju, Huang; Hongda, Chen

    2010-04-01

    A fully-differential bandpass CMOS (complementary metal oxide semiconductor) preamplifier for extracellular neural recording is presented. The capacitive-coupled and capacitive-feedback topology is adopted. The preamplifier has a midband gain of 20.4 dB and a DC gain of 0. The -3 dB upper cut-off frequency of the preamplifier is 6.7 kHz. The lower cut-off frequency can be adjusted for amplifying the field or action potentials located in different bands. It has an input-referred noise of 8.2 μVrms integrated from 0.15 Hz to 6.7 kHz for recording the local field potentials and the mixed neural spikes with a power dissipation of 23.1 μW from a 3.3 V supply. A bandgap reference circuitry is also designed for providing the biasing voltage and current. The 0.22 mm2 prototype chip, including the preamplifier and its biasing circuitry, is fabricated in the 0.35-μm N-well CMOS 2P4M process.

  17. Neural Network-Based Solutions for Stochastic Optimal Control Using Path Integrals.

    Science.gov (United States)

    Rajagopal, Karthikeyan; Balakrishnan, Sivasubramanya Nadar; Busemeyer, Jerome R

    2017-03-01

    In this paper, an offline approximate dynamic programming approach using neural networks is proposed for solving a class of finite horizon stochastic optimal control problems. There are two approaches available in the literature, one based on stochastic maximum principle (SMP) formalism and the other based on solving the stochastic Hamilton-Jacobi-Bellman (HJB) equation. However, in the presence of noise, the SMP formalism becomes complex and results in having to solve a couple of backward stochastic differential equations. Hence, current solution methodologies typically ignore the noise effect. On the other hand, the inclusion of noise in the HJB framework is very straightforward. Furthermore, the stochastic HJB equation of a control-affine nonlinear stochastic system with a quadratic control cost function and an arbitrary state cost function can be formulated as a path integral (PI) problem. However, due to curse of dimensionality, it might not be possible to utilize the PI formulation for obtaining comprehensive solutions over the entire operating domain. A neural network structure called the adaptive critic design paradigm is used to effectively handle this difficulty. In this paper, a novel adaptive critic approach using the PI formulation is proposed for solving stochastic optimal control problems. The potential of the algorithm is demonstrated through simulation results from a couple of benchmark problems.

  18. Neural substrates of reliability-weighted visual-tactile multisensory integration

    Directory of Open Access Journals (Sweden)

    Michael S Beauchamp

    2010-06-01

    Full Text Available As sensory systems deteriorate in aging or disease, the brain must relearn the appropriate weights to assign each modality during multisensory integration. Using blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI of human subjects, we tested a model for the neural mechanisms of sensory weighting, termed “weighted connections”. This model holds that the connection weights between early and late areas vary depending on the reliability of the modality, independent of the level of early sensory cortex activity. When subjects detected viewed and felt touches to the hand, a network of brain areas was active, including visual areas in lateral occipital cortex, somatosensory areas in inferior parietal lobe, and multisensory areas in the intraparietal sulcus (IPS. In agreement with the weighted connection model, the connection weight measured with structural equation modeling between somatosensory cortex and IPS increased for somatosensory-reliable stimuli, and the connection weight between visual cortex and IPS increased for visual-reliable stimuli. This double dissociation of connection strengths was similar to the pattern of behavioral responses during incongruent multisensory stimulation, suggesting that weighted connections may be a neural mechanism for behavioral reliability weighting.for behavioral reliability weighting.

  19. Impulsive synchronization of Markovian jumping randomly coupled neural networks with partly unknown transition probabilities via multiple integral approach.

    Science.gov (United States)

    Chandrasekar, A; Rakkiyappan, R; Cao, Jinde

    2015-10-01

    This paper studies the impulsive synchronization of Markovian jumping randomly coupled neural networks with partly unknown transition probabilities via multiple integral approach. The array of neural networks are coupled in a random fashion which is governed by Bernoulli random variable. The aim of this paper is to obtain the synchronization criteria, which is suitable for both exactly known and partly unknown transition probabilities such that the coupled neural network is synchronized with mixed time-delay. The considered impulsive effects can be synchronized at partly unknown transition probabilities. Besides, a multiple integral approach is also proposed to strengthen the Markovian jumping randomly coupled neural networks with partly unknown transition probabilities. By making use of Kronecker product and some useful integral inequalities, a novel Lyapunov-Krasovskii functional was designed for handling the coupled neural network with mixed delay and then impulsive synchronization criteria are solvable in a set of linear matrix inequalities. Finally, numerical examples are presented to illustrate the effectiveness and advantages of the theoretical results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. MD-SeeGH: a platform for integrative analysis of multi-dimensional genomic data

    Directory of Open Access Journals (Sweden)

    Ng Raymond T

    2008-05-01

    Full Text Available Abstract Background Recent advances in global genomic profiling methodologies have enabled multi-dimensional characterization of biological systems. Complete analysis of these genomic profiles require an in depth look at parallel profiles of segmental DNA copy number status, DNA methylation state, single nucleotide polymorphisms, as well as gene expression profiles. Due to the differences in data types it is difficult to conduct parallel analysis of multiple datasets from diverse platforms. Results To address this issue, we have developed an integrative genomic analysis platform MD-SeeGH, a software tool that allows users to rapidly and directly analyze genomic datasets spanning multiple genomic experiments. With MD-SeeGH, users have the flexibility to easily update datasets in accordance with new genomic builds, make a quality assessment of data using the filtering features, and identify genetic alterations within single or across multiple experiments. Multiple sample analysis in MD-SeeGH allows users to compare profiles from many experiments alongside tracks containing detailed localized gene information, microRNA, CpG islands, and copy number variations. Conclusion MD-SeeGH is a new platform for the integrative analysis of diverse microarray data, facilitating multiple profile analyses and group comparisons.

  1. Isolation of recombinant field strains of Marek's disease virus integrated with reticuloendotheliosis virus genome fragments

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhi; CUI; Zhizhong

    2005-01-01

    Two Marek's disease virus (MDV) field strains were isolated from chickens with tumors independently from Guangdong and Guangxi provinces, and it was confirmed that there were no co-infections with reticuloendotheliosis viruses (REV) in chicken embryo fibroblast cells (CEF) in indirect fluorescence antibody test (IFA) with REV-specific monoclonal antibodies. By dot blot hybridization and PCR of genomic DNA of MDV-infected CEF, it was indicated that LTR fragments of REV genome were integrated into genome of these two MDV field strains. To amplify and clone the integrated REV LTR with MDV sequence at the junction, 4 primers from REV LTR and 7 primers from MDV genome fragment with REV LTR insertion hot points were synthesized and 28 (4x7) pairs of primers (one from REV and another from MDV for each pair) were used in PCR while using the genomic DNA of both strains as the templates. The sequence data demonstrated that both recombinant field strains contained the same REV LTR inserted into MDV at the identical sites in US fragment of the genomes. From the above, it was speculated that both recombinant field MDVs were originated from a same recombinant virus and spread among chicken flocks in two provinces.

  2. Neural CMOS-integrated circuit and its application to data classification.

    Science.gov (United States)

    Göknar, Izzet Cem; Yildiz, Merih; Minaei, Shahram; Deniz, Engin

    2012-05-01

    Implementation and new applications of a tunable complementary metal-oxide-semiconductor-integrated circuit (CMOS-IC) of a recently proposed classifier core-cell (CC) are presented and tested with two different datasets. With two algorithms-one based on Fisher's linear discriminant analysis and the other based on perceptron learning, used to obtain CCs' tunable parameters-the Haberman and Iris datasets are classified. The parameters so obtained are used for hard-classification of datasets with a neural network structured circuit. Classification performance and coefficient calculation times for both algorithms are given. The CC has 6-ns response time and 1.8-mW power consumption. The fabrication parameters used for the IC are taken from CMOS AMS 0.35-μm technology.

  3. Analog integrated circuits for the Lotka-Volterra competitive neural networks.

    Science.gov (United States)

    Asai, T; Ohtani, M; Yonezu, H

    1999-01-01

    A subthreshold MOS integrated circuit (IC) is designed and fabricated for implementing a competitive neural network of the Lotka-Volterra (LV) type which is derived from conventional membrane dynamics of neurons and is used for the selection of external inputs. The steady-state solutions to the LV equation can be classified into three types, each of which represents qualitatively different selection behavior. Among the solutions, the winners-share-all (WSA) solution in which a certain number of neurons remain activated in steady states is particularly useful owing to robustness in the selection of inputs from a noisy environment. The measured results of the fabricated LV IC's agree well with the theoretical prediction as long as the influence of device mismatches is small. Furthermore, results of extensive circuit simulations prove that the large-scale LV circuit producing the WSA solution does exhibit a reliable selection compared with winner-take-all circuits, in the possible presence of device mismatches.

  4. FPGA IMPLEMENTATION OF ADAPTIVE INTEGRATED SPIKING NEURAL NETWORK FOR EFFICIENT IMAGE RECOGNITION SYSTEM

    Directory of Open Access Journals (Sweden)

    T. Pasupathi

    2014-05-01

    Full Text Available Image recognition is a technology which can be used in various applications such as medical image recognition systems, security, defense video tracking, and factory automation. In this paper we present a novel pipelined architecture of an adaptive integrated Artificial Neural Network for image recognition. In our proposed work we have combined the feature of spiking neuron concept with ANN to achieve the efficient architecture for image recognition. The set of training images are trained by ANN and target output has been identified. Real time videos are captured and then converted into frames for testing purpose and the image were recognized. The machine can operate at up to 40 frames/sec using images acquired from the camera. The system has been implemented on XC3S400 SPARTAN-3 Field Programmable Gate Arrays.

  5. A High Input Impedance Low Noise Integrated Front-End Amplifier for Neural Monitoring.

    Science.gov (United States)

    Zhou, Zhijun; Warr, Paul A

    2016-12-01

    Within neural monitoring systems, the front-end amplifier forms the critical element for signal detection and pre-processing, which determines not only the fidelity of the biosignal, but also impacts power consumption and detector size. In this paper, a novel combined feedback loop-controlled approach is proposed to compensate for input leakage currents generated by low noise amplifiers when in integrated circuit form alongside signal leakage into the input bias network. This loop topology ensures the Front-End Amplifier (FEA) maintains a high input impedance across all manufacturing and operational variations. Measured results from a prototype manufactured on the AMS 0.35 [Formula: see text] CMOS technology is provided. This FEA consumes 3.1 [Formula: see text] in 0.042 [Formula: see text], achieves input impedance of 42 [Formula: see text], and 18.2 [Formula: see text] input-referred noise.

  6. Using neural networks and Dyna algorithm for integrated planning, reacting and learning in systems

    Science.gov (United States)

    Lima, Pedro; Beard, Randal

    1992-01-01

    The traditional AI answer to the decision making problem for a robot is planning. However, planning is usually CPU-time consuming, depending on the availability and accuracy of a world model. The Dyna system generally described in earlier work, uses trial and error to learn a world model which is simultaneously used to plan reactions resulting in optimal action sequences. It is an attempt to integrate planning, reactive, and learning systems. The architecture of Dyna is presented. The different blocks are described. There are three main components of the system. The first is the world model used by the robot for internal world representation. The input of the world model is the current state and the action taken in the current state. The output is the corresponding reward and resulting state. The second module in the system is the policy. The policy observes the current state and outputs the action to be executed by the robot. At the beginning of program execution, the policy is stochastic and through learning progressively becomes deterministic. The policy decides upon an action according to the output of an evaluation function, which is the third module of the system. The evaluation function takes the following as input: the current state of the system, the action taken in that state, the resulting state, and a reward generated by the world which is proportional to the current distance from the goal state. Originally, the work proposed was as follows: (1) to implement a simple 2-D world where a 'robot' is navigating around obstacles, to learn the path to a goal, by using lookup tables; (2) to substitute the world model and Q estimate function Q by neural networks; and (3) to apply the algorithm to a more complex world where the use of a neural network would be fully justified. In this paper, the system design and achieved results will be described. First we implement the world model with a neural network and leave Q implemented as a look up table. Next, we use a

  7. Integrative analysis of neuroblastoma and pheochromocytoma genomics data

    Directory of Open Access Journals (Sweden)

    Szabó Peter M

    2012-10-01

    Full Text Available Abstract Background Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory. Methods Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software. Results Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1α and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma. Conclusions These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic

  8. Transcription factor binding sites are genetic determinants of retroviral integration in the human genome.

    Directory of Open Access Journals (Sweden)

    Barbara Felice

    Full Text Available Gamma-retroviruses and lentiviruses integrate non-randomly in mammalian genomes, with specific preferences for active chromatin, promoters and regulatory regions. Gene transfer vectors derived from gamma-retroviruses target at high frequency genes involved in the control of growth, development and differentiation of the target cell, and may induce insertional tumors or pre-neoplastic clonal expansions in patients treated by gene therapy. The gene expression program of the target cell is apparently instrumental in directing gamma-retroviral integration, although the molecular basis of this phenomenon is poorly understood. We report a bioinformatic analysis of the distribution of transcription factor binding sites (TFBSs flanking >4,000 integrated proviruses in human hematopoietic and non-hematopoietic cells. We show that gamma-retroviral, but not lentiviral vectors, integrate in genomic regions enriched in cell-type specific subsets of TFBSs, independently from their relative position with respect to genes and transcription start sites. Analysis of sequences flanking the integration sites of Moloney leukemia virus (MLV- and human immunodeficiency virus (HIV-derived vectors carrying mutations in their long terminal repeats (LTRs, and of HIV vectors packaged with an MLV integrase, indicates that the MLV integrase and LTR enhancer are the viral determinants of the selection of TFBS-rich regions in the genome. This study identifies TFBSs as differential genomic determinants of retroviral target site selection in the human genome, and suggests that transcription factors binding the LTR enhancer may synergize with the integrase in tethering retroviral pre-integration complexes to transcriptionally active regulatory regions. Our data indicate that gamma-retroviruses and lentiviruses have evolved dramatically different strategies to interact with the host cell chromatin, and predict a higher risk in using gamma-retroviral vs. lentiviral vectors for human

  9. Neural mechanisms underlying the integration of situational information into attribution outcomes.

    Science.gov (United States)

    Brosch, Tobias; Schiller, Daniela; Mojdehbakhsh, Rachel; Uleman, James S; Phelps, Elizabeth A

    2013-08-01

    When forming impressions and trying to figure out why other people behave the way they do, we should take into account not only dispositional factors (i.e., personality traits) but also situational constraints as potential causes for a behavior. However, in their attributions, people often ignore the importance of situational factors. To investigate the neural mechanisms underlying the integration of situational information into attributions, we decomposed the attribution process by separately presenting information about behaviors and about the situational circumstances in which they occur. After reading the information, participants judged whether dispositional or situational causes explained the behavior (attribution), and how much they liked the person described in the scenario (affective evaluation). The dorsolateral prefrontal cortex showed increased blood oxygenation-level-dependent activation during the encoding of situational information when the resulting attribution was situational, relative to when the attribution was dispositional, potentially reflecting a controlled process that integrates situational information into attributions. Interestingly, attributions were strongly linked to subsequent affective evaluations, with the dorsomedial prefrontal cortex emerging as potential substrate of the integration of attributions and affective evaluations. Our findings demonstrate how top-down control processes regulate impression formation when situational information is taken into account to understand others.

  10. Auditory processing disorders: relationship to cognitive processes and underlying auditory neural integrity.

    Science.gov (United States)

    Allen, Prudence; Allan, Chris

    2014-02-01

    Auditory processing disorder (APD) in children has been reported and discussed in the clinical and research literature for many years yet there remains poor agreement on diagnostic criteria, the relationship between APD and cognitive skills, and the importance of assessing underlying neural integrity. The present study used a repeated measures design to examine the relationship between a clinical APD diagnosis achieved with behavioral tests used in many clinics, cognitive abilities measured with standardized tests of intelligence, academic achievement, language, phonology, memory and attention and measures of auditory neural integrity as measured with acoustic reflex thresholds and auditory brainstem responses. Participants were 63 children, 7-17 years of age, who reported listening difficulties in spite of normal hearing thresholds. Parents/guardians completed surveys about the child's auditory and attention behavior while children completed an audiologic examination that included 5 behavioral tests of auditory processing ability. Standardized tests that examined intelligence, academic achievement, language, phonology, memory and attention, and objective tests auditory function included crossed and uncrossed acoustic reflex thresholds and auditory brainstem responses (ABR) were also administered to each child. Forty of the children received an APD diagnosis based on the 5 behavioral tests and 23 did not. The groups of children performed similarly on intelligence measures but the children with an APD diagnosis tended to perform more poorly on other cognitive measures. Auditory brainstem responses and acoustic reflex thresholds were often abnormal in both groups of children. Results of this study suggest that a purely behavioral test battery may be insufficient to accurately identify all children with auditory processing disorders. Physiologic test measures, including acoustic reflex and auditory brainstem response tests, are important indicators of auditory

  11. Neural basis of the time window for subjective motor-auditory integration

    Directory of Open Access Journals (Sweden)

    Koichi eToida

    2016-01-01

    Full Text Available Temporal contiguity between an action and corresponding auditory feedback is crucial to the perception of self-generated sound. However, the neural mechanisms underlying motor–auditory temporal integration are unclear. Here, we conducted four experiments with an oddball paradigm to examine the specific event-related potentials (ERPs elicited by delayed auditory feedback for a self-generated action. The first experiment confirmed that a pitch-deviant auditory stimulus elicits mismatch negativity (MMN and P300, both when it is generated passively and by the participant’s action. In our second and third experiments, we investigated the ERP components elicited by delayed auditory feedback of for a self-generated action. We found that delayed auditory feedback elicited an enhancement of P2 (enhanced-P2 and a N300 component, which were apparently different from the MMN and P300 components observed in the first experiment. We further investigated the sensitivity of the enhanced-P2 and N300 to delay length in our fourth experiment. Strikingly, the amplitude of the N300 increased as a function of the delay length. Additionally, the N300 amplitude was significantly correlated with the conscious detection of the delay (the 50% detection point was around 200 ms, and hence reduction in the feeling of authorship of the sound (the sense of agency. In contrast, the enhanced-P2 was most prominent in short-delay (≤ 200 ms conditions and diminished in long-delay conditions. Our results suggest that different neural mechanisms are employed for the processing of temporally-deviant and pitch-deviant auditory feedback. Additionally, the temporal window for subjective motor–auditory integration is likely about 200 ms, as indicated by these auditory ERP components.

  12. Influence of the antifolate drug Methotrexate on the development of murine neural tube defects and genomic instability.

    Science.gov (United States)

    Zhao, Jie; Guan, Tao; Wang, Jianhua; Xiang, Qian; Wang, Mingsheng; Wang, Xiuwei; Guan, Zhen; Xie, Qiu; Niu, Bo; Zhang, Ting

    2013-09-01

    Impaired folate metabolism is considered a risk factor for neural tube defects (NTDs). However, the relationship between folate deficiency and the risk of NTDs remains unclear, because experimentally induced dietary folate deficiency is insufficient to cause NTDs in non-mutant mice. Methotrexate (MTX) is a specific folate antagonist that competitively inhibits dihydrofolate reductase (DHFR) activity. The objective of this study was to develop a folate dysmetabolism murine model, and study the development of NTDs and its mechanism. Pregnant mice were injected with different doses of MTX [0, 0.5, 1.0, 3.0, 4.5 and 6.0 mg kg(-1) body weight (b/w) intraperitoneally (i.p.)] on gestational day 7.5 and sacrificed on gestational day 11.5. DHFR activity in embryonic tissues was detected, and folate concentrations were analyzed using LC/MS/MS. Copy number variations (CNVs) in neural tube tissues were detected using array comparative genomic hybridization (aCGH). A dose of MTX 4.5 mg kg(-1) b/w, resulted in the highest incidence of NTDs (31.4%) compared with the other groups, and DHFR activities, 5-MeTHF and 5-FoTHF concentrations in embryonic tissues decreased significantly after MTX injection. Furthermore, we found three high-confidence CNVs on chromosome X using aCGH, which was confirmed by RT-PCR and MassARRAY. These results indicate that MTX could cause a folate-associated dysmetabolism, which is similar to that of dietary folate deficiency in mice. The presence of CNVs in neural tube tissues was associated with the development of NTDs.

  13. PGSB/MIPS PlantsDB Database Framework for the Integration and Analysis of Plant Genome Data.

    Science.gov (United States)

    Spannagl, Manuel; Nussbaumer, Thomas; Bader, Kai; Gundlach, Heidrun; Mayer, Klaus F X

    2017-01-01

    Plant Genome and Systems Biology (PGSB), formerly Munich Institute for Protein Sequences (MIPS) PlantsDB, is a database framework for the integration and analysis of plant genome data, developed and maintained for more than a decade now. Major components of that framework are genome databases and analysis resources focusing on individual (reference) genomes providing flexible and intuitive access to data. Another main focus is the integration of genomes from both model and crop plants to form a scaffold for comparative genomics, assisted by specialized tools such as the CrowsNest viewer to explore conserved gene order (synteny). Data exchange and integrated search functionality with/over many plant genome databases is provided within the transPLANT project.

  14. Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1

    Directory of Open Access Journals (Sweden)

    Martín Yusé

    2011-12-01

    Full Text Available Abstract Maintenance of genomic integrity is essential for cell survival. Specifically, during DNA replication cells use a complex network of mechanisms that prevents genomic instability. Recently, we and others identified Wee1, a serine/threonine and tyrosine kinase, as a new modulator of the genomic stability during S phase. Loss of its activity causes a general DNA damage response activation and a decrease in replication fork speed. These effects are counteracted by the downregulation of the endonuclease complex Mus81-Eme1, showing a new link between this endonuclease and Wee1 during DNA replication. Here we discuss the function of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex.

  15. Genome-wide copy number profiling of mouse neural stem cells during differentiation

    Directory of Open Access Journals (Sweden)

    U. Fischer

    2015-09-01

    Full Text Available There is growing evidence that gene amplifications were present in neural stem and progenitor cells during differentiation. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of mouse neural stem cells using TGF-ß and FCS for differentiation induction. Array data were deposited in GEO (Gene Expression Omnibus, NCBI under accession number GSE35523. Here, we describe in detail the cell culture features and our TaqMan qPCR-experiments to validate the array-CGH analysis. Interpretation of array-CGH experiments regarding gene amplifications in mouse and further detailed analysis of amplified chromosome regions associated with these experiments were published by Fischer and colleagues in Oncotarget (Fischer et al., 2015. We provide additional information on deleted chromosome regions during differentiation and give an impressive overview on copy number changes during differentiation induction at a time line.

  16. Improved bacteriophage genome data is necessary for integrating viral and bacterial ecology.

    Science.gov (United States)

    Bibby, Kyle

    2014-02-01

    The recent rise in "omics"-enabled approaches has lead to improved understanding in many areas of microbial ecology. However, despite the importance that viruses play in a broad microbial ecology context, viral ecology remains largely not integrated into high-throughput microbial ecology studies. A fundamental hindrance to the integration of viral ecology into omics-enabled microbial ecology studies is the lack of suitable reference bacteriophage genomes in reference databases-currently, only 0.001% of bacteriophage diversity is represented in genome sequence databases. This commentary serves to highlight this issue and to promote bacteriophage genome sequencing as a valuable scientific undertaking to both better understand bacteriophage diversity and move towards a more holistic view of microbial ecology.

  17. An IKKα-Nucleophosmin Axis Utilizes Inflammatory Signaling to Promote Genome Integrity

    Directory of Open Access Journals (Sweden)

    Xiaojun Xia

    2013-12-01

    Full Text Available The inflammatory microenvironment promotes skin tumorigenesis. However, the mechanisms by which cells protect themselves from inflammatory signals are unknown. Downregulation of IKKα promotes skin tumor progression from papillomas to squamous cell carcinomas, which is frequently accompanied by genomic instability, including aneuploid chromosomes and extra centrosomes. In this study, we found that IKKα promoted oligomerization of nucleophosmin (NPM, a negative centrosome duplication regulator, which further enhanced NPM and centrosome association, inhibited centrosome amplification, and maintained genome integrity. Levels of NPM hexamers and IKKα were conversely associated with skin tumor progression. Importantly, proinflammatory cytokine-induced IKKα activation promoted the formation of NPM oligomers and reduced centrosome numbers in mouse and human cells, whereas kinase-dead IKKα blocked this connection. Therefore, our findings suggest a mechanism in which an IKKα-NPM axis may use inflammatory signals to suppress centrosome amplification, promote genomic integrity, and prevent tumor progression.

  18. Integrating Genomic Data Sets for Knowledge Discovery: An Informed Approach to Management of Captive Endangered Species.

    Science.gov (United States)

    Irizarry, Kristopher J L; Bryant, Doug; Kalish, Jordan; Eng, Curtis; Schmidt, Peggy L; Barrett, Gini; Barr, Margaret C

    2016-01-01

    Many endangered captive populations exhibit reduced genetic diversity resulting in health issues that impact reproductive fitness and quality of life. Numerous cost effective genomic sequencing and genotyping technologies provide unparalleled opportunity for incorporating genomics knowledge in management of endangered species. Genomic data, such as sequence data, transcriptome data, and genotyping data, provide critical information about a captive population that, when leveraged correctly, can be utilized to maximize population genetic variation while simultaneously reducing unintended introduction or propagation of undesirable phenotypes. Current approaches aimed at managing endangered captive populations utilize species survival plans (SSPs) that rely upon mean kinship estimates to maximize genetic diversity while simultaneously avoiding artificial selection in the breeding program. However, as genomic resources increase for each endangered species, the potential knowledge available for management also increases. Unlike model organisms in which considerable scientific resources are used to experimentally validate genotype-phenotype relationships, endangered species typically lack the necessary sample sizes and economic resources required for such studies. Even so, in the absence of experimentally verified genetic discoveries, genomics data still provides value. In fact, bioinformatics and comparative genomics approaches offer mechanisms for translating these raw genomics data sets into integrated knowledge that enable an informed approach to endangered species management.

  19. Decoding the genome with an integrative analysis tool: combinatorial CRM Decoder.

    Science.gov (United States)

    Kang, Keunsoo; Kim, Joomyeong; Chung, Jae Hoon; Lee, Daeyoup

    2011-09-01

    The identification of genome-wide cis-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called 'trace code', and subsequently uses the trace code to pinpoint putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from 17 independent mouse studies, CCD successfully catalogued ∼12 600 CRMs (five distinct classes) including polycomb repressive complex 2 target sites as well as imprinting control regions. Interestingly, we discovered that ∼4% of the identified CRMs belong to at least two different classes named 'multi-functional CRM', suggesting their functional importance for regulating spatiotemporal gene expression. From these examples, we show that CCD can be applied to any potential genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs in various species.

  20. Barriers and potential solutions for Critical Zone data integration between environmental genomics and the geosciences

    Science.gov (United States)

    Aronson, E. L.; Meyer, F.; Packman, A. I.; Mayorga, E.

    2015-12-01

    The Earth's permeable near-surface layer from bedrock to canopy is referred to as the Critical Zone (CZ). Integration of bio- and geoscience data is critical for understanding physical, biological and chemical interactions in the CZ. Genomic and meta-genomic scientists study organisms both in laboratory settings and in the environment, in order to understand the interactions of organisms with the environment. Geoscientists are using environmental data to describe and model dynamics of physical and chemical properties. Yet, there is no agreed upon method for integrating genomic and environmental data to address interactions of living and non-living components of the CZ. There are standards for data interchange being developed in the geosciences and genomics sciences, via standards organization such as the Open Geospatial Consortium (OGC), as well as by research communities in biogeochemistry, hydrology, climatology, and other fields. These are in parallel to, but typically not in coordination with the standards the Genomics Standards Consortium (GSC) is developing for genomics. In addition, efforts are being made to allow for intercompatability of these CZ data with data generated by NEON, Inc. The interoperability of these types of data is limited with current software and cyberinfrastructure. A group of CZ geoscientists, environmental genomic scientists and cyberinfrastructure scientists are coming together to develop a set of common data collection and integration methods and sets of common standards. The data generated by this effort across multiple CZ sites (including the US CZ Observatories, or CZOs) around the world, along with NEON facility data, will be used to test EarthCube (an NSF initiative to develop cyberinfrastructure for the geosciences) cyberinfrastructure, with the goal of bridging this gap in standards and interoperability. Potential solutions to these issues of interoperability will be presented, and a way forward will be described.

  1. Rice TOGO Browser: A platform to retrieve integrated information on rice functional and applied genomics.

    Science.gov (United States)

    Nagamura, Yoshiaki; Antonio, Baltazar A; Sato, Yutaka; Miyao, Akio; Namiki, Nobukazu; Yonemaru, Jun-ichi; Minami, Hiroshi; Kamatsuki, Kaori; Shimura, Kan; Shimizu, Yuji; Hirochika, Hirohiko

    2011-02-01

    The Rice TOGO Browser is an online public resource designed to facilitate integration and visualization of mapping data of bacterial artificial chromosome (BAC)/P1-derived artificial chromosome (PAC) clones, genes, restriction fragment length polymorphism (RFLP)/simple sequence repeat (SSR) markers and phenotype data represented as quantitative trait loci (QTLs) onto the genome sequence, and to provide a platform for more efficient utilization of genome information from the point of view of applied genomics as well as functional genomics. Three search options, namely keyword search, region search and trait search, generate various types of data in a user-friendly interface with three distinct viewers, a chromosome viewer, an integrated map viewer and a sequence viewer, thereby providing the opportunity to view the position of genes and/or QTLs at the chromosomal level and to retrieve any sequence information in a user-defined genome region. Furthermore, the gene list, marker list and genome sequence in a specified region delineated by RFLP/SSR markers and any sequences designed as primers can be viewed and downloaded to support forward genetics approaches. An additional feature of this database is the graphical viewer for BLAST search to reveal information not only for regions with significant sequence similarity but also for regions adjacent to those with similarity but with no hits between sequences. An easy to use and intuitive user interface can help a wide range of users in retrieving integrated mapping information including agronomically important traits on the rice genome sequence. The database can be accessed at http://agri-trait.dna.affrc.go.jp/.

  2. Dissecting the brown adipogenic regulatory network using integrative genomics

    Science.gov (United States)

    Pradhan, Rachana N.; Bues, Johannes J.; Gardeux, Vincent; Schwalie, Petra C.; Alpern, Daniel; Chen, Wanze; Russeil, Julie; Raghav, Sunil K.; Deplancke, Bart

    2017-01-01

    Brown adipocytes regulate energy expenditure via mitochondrial uncoupling, which makes them attractive therapeutic targets to tackle obesity. However, the regulatory mechanisms underlying brown adipogenesis are still poorly understood. To address this, we profiled the transcriptome and chromatin state during mouse brown fat cell differentiation, revealing extensive gene expression changes and chromatin remodeling, especially during the first day post-differentiation. To identify putatively causal regulators, we performed transcription factor binding site overrepresentation analyses in active chromatin regions and prioritized factors based on their expression correlation with the bona-fide brown adipogenic marker Ucp1 across multiple mouse and human datasets. Using loss-of-function assays, we evaluated both the phenotypic effect as well as the transcriptomic impact of several putative regulators on the differentiation process, uncovering ZFP467, HOXA4 and Nuclear Factor I A (NFIA) as novel transcriptional regulators. Of these, NFIA emerged as the regulator yielding the strongest molecular and cellular phenotypes. To examine its regulatory function, we profiled the genomic localization of NFIA, identifying it as a key early regulator of terminal brown fat cell differentiation. PMID:28181539

  3. Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis

    NARCIS (Netherlands)

    Low, T.Y.; van Heesch, S.; van den Toorn, H.; Giansanti, P.; Cristobal, A.; Toonen, P.; Schafer, S.; Hubner, N.; van Breukelen, B.; Mohammed, S.; Cuppen, E.; Heck, A.J.R.; Guryev, V.

    2013-01-01

    Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtain

  4. BiGG Models: A platform for integrating, standardizing and sharing genome-scale models

    DEFF Research Database (Denmark)

    2016-01-01

    Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized...

  5. Challenges in experimental data integration within genome-scale metabolic models

    Directory of Open Access Journals (Sweden)

    Képès François

    2010-04-01

    Full Text Available Abstract A report of the meeting "Challenges in experimental data integration within genome-scale metabolic models", Institut Henri Poincaré, Paris, October 10-11 2009, organized by the CNRS-MPG joint program in Systems Biology.

  6. An integrated framework for discovery and genotyping of genomic variants from high-throughput sequencing experiments

    NARCIS (Netherlands)

    Duitama, Jorge; Quintero, Juan Camilo; Cruz, Daniel Felipe; Quintero, Constanza; Hubmann, Georg; Foulquié-Moreno, Maria R.; Verstrepen, Kevin J.; Thevelein, Johan M.; Tohme, Joe

    2014-01-01

    Recent advances in high-throughput sequencing (HTS) technologies and computing capacity have produced unprecedented amounts of genomic data that have unraveled the genetics of phenotypic variability in several species. However, operating and integrating current software tools for data analysis still

  7. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analys

  8. Ori-Finder 2, an integrated tool to predict replication origins in the archaeal genomes

    Directory of Open Access Journals (Sweden)

    Hao eLuo

    2014-09-01

    Full Text Available DNA replication is one of the most basic processes in all three domains of cellular life. With the advent of the post-genomic era, the increasing number of complete archaeal genomes has created an opportunity for exploration of the molecular mechanisms for initiating cellular DNA replication by in vivo experiments as well as in silico analysis. However, the location of replication origins (oriCs in many sequenced archaeal genomes remains unknown. We present a web-based tool Ori-Finder 2 to predict oriCs in the archaeal genomes automatically, based on the integrated method comprising the analysis of base composition asymmetry using the Z-curve method, the distribution of Origin Recognition Boxes (ORBs identified by FIMO tool, and the occurrence of genes frequently close to oriCs. The web server is also able to analyze the unannotated genome sequences by integrating with gene prediction pipelines and BLAST software for gene identification and function annotation. The result of the predicted oriCs is displayed as an HTML table, which offers an intuitive way to browse the result in graphical and tabular form. The software presented here is accurate for the genomes with single oriC, but it does not necessarily find all the origins of replication for the genomes with multiple oriCs. Ori-Finder 2 aims to become a useful platform for the identification and analysis of oriCs in the archaeal genomes, which would provide insight into the replication mechanisms in archaea. The web server is freely available at http://tubic.tju.edu.cn/Ori-Finder2/.

  9. Neural mechanism of oculomotor horizontal velocity-to- position temporal integration

    Science.gov (United States)

    Aksay, Emre R. F.

    Storage of briefly presented information in ``working'' memory correlates with persistent firing in the brain. Persistent activity in response to transient stimulation is a form of neural temporal integration. Here, the mechanism of temporal integration was explored in the oculomotor velocity-to-position neural integrator (VPNI), where persistent activity is used to maintain eye position and fixation. Extracellular and intracellular electrophysiology, single-cell dye- labeling, and pharmacological inactivation were performed in awake behaving goldfish while monitoring eye motion with the scleral search-coil method. Neurons identified within a compact subnucleus in the medulla designated as Area I are part of the VPNI for horizontal eye movements. Neurons fired tonically during fixations, with tonic rate higher for lateral eye positions and no discharge below a threshold position value. Dye-labeled somata were localized in a 350 micron extent of the inferior reticular formation. Axons either projected ipsilaterally to abducens motoneurons, or crossed the midline and projected toward the contralateral Area I and abducens. Bilateral inactivation of Area I induced inability to maintain eccentric gaze. During intracellular recording, step changes in eye position and firing rate were accompanied by steps in underlying membrane potential. Steps remained when neurons were hyperpolarized below action potential threshold. Perturbation with brief intracellular current pulses only induced transient changes in firing rate and potential. Membrane potential fluctuations were greater during more depolarized steps. These results suggest that steps are generated by synaptic input changes rather than intrinsic properties like membrane multistability. Spiking of unilateral pairs was positively correlated with 0-10 ms lag. Bilateral pairs were negatively correlated with 0-10 ms lag. These results are consistent with excitatory connections between unilateral pairs and inhibitory

  10. Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes.

    Directory of Open Access Journals (Sweden)

    Vladimir A Belyi

    Full Text Available Vertebrate genomes contain numerous copies of retroviral sequences, acquired over the course of evolution. Until recently they were thought to be the only type of RNA viruses to be so represented, because integration of a DNA copy of their genome is required for their replication. In this study, an extensive sequence comparison was conducted in which 5,666 viral genes from all known non-retroviral families with single-stranded RNA genomes were matched against the germline genomes of 48 vertebrate species, to determine if such viruses could also contribute to the vertebrate genetic heritage. In 19 of the tested vertebrate species, we discovered as many as 80 high-confidence examples of genomic DNA sequences that appear to be derived, as long ago as 40 million years, from ancestral members of 4 currently circulating virus families with single strand RNA genomes. Surprisingly, almost all of the sequences are related to only two families in the Order Mononegavirales: the Bornaviruses and the Filoviruses, which cause lethal neurological disease and hemorrhagic fevers, respectively. Based on signature landmarks some, and perhaps all, of the endogenous virus-like DNA sequences appear to be LINE element-facilitated integrations derived from viral mRNAs. The integrations represent genes that encode viral nucleocapsid, RNA-dependent-RNA-polymerase, matrix and, possibly, glycoproteins. Integrations are generally limited to one or very few copies of a related viral gene per species, suggesting that once the initial germline integration was obtained (or selected, later integrations failed or provided little advantage to the host. The conservation of relatively long open reading frames for several of the endogenous sequences, the virus-like protein regions represented, and a potential correlation between their presence and a species' resistance to the diseases caused by these pathogens, are consistent with the notion that their products provide some important

  11. A Neural Systems-Based Neurobiology and Neuropsychiatry Course: Integrating Biology, Psychodynamics, and Psychology in the Psychiatric Curriculum

    Science.gov (United States)

    Lacy, Timothy; Hughes, John D.

    2006-01-01

    Objective: Psychotherapy and biological psychiatry remain divided in psychiatry residency curricula. Behavioral neurobiology and neuropsychiatry provide a systems-level framework that allows teachers to integrate biology, psychodynamics, and psychology. Method: The authors detail the underlying assumptions and outline of a neural systems-based…

  12. Integrating Imaging spectrometry and Neural Networks to map tropical grass quality in the Kruger National Park, South Africa

    NARCIS (Netherlands)

    Mutanga, O.; Skidmore, A.K.

    2004-01-01

    A new integrated approach, involving continuum-removed absorption features, the red edge position and neural networks, is developed and applied to map grass nitrogen concentration in an African savanna rangeland. Nitrogen, which largely determines the nutritional quality of grasslands, is commonly t

  13. The nucleolus—guardian of cellular homeostasis and genome integrity.

    Science.gov (United States)

    Grummt, Ingrid

    2013-12-01

    All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.

  14. INTEGRATIVE COMPUTER ANALYSIS OF ANTISENSE TRANSCRIPTS AND miRNA TARGETS IN PLANT GENOMES

    Directory of Open Access Journals (Sweden)

    Orlov Y.L.

    2012-08-01

    Full Text Available Non-coding RNA, including small interfering RNAs (siRNAs, are important components of gene expression in eukaryotes, forming a regulatory network. miRNAs are expressed through nucleolytic maturation of hairpin precursors transcribed by RNA Polymerase II or III. Such transcripts are involved in post-transcriptional gene regulation in plants, fungi and animals. miRNAs bind to target RNA transcripts and guide their cleavage (mostly for plants or act to prevent translation. siRNAs act via a similar mechanism of cleavage of their target genes, but they also can direct genomic DNA methylation and chromatin remodeling. It is estimated that large fraction, up to 30% of all human genes also may be post-transcriptionally regulated by miRNAs. For plant genomes numbers could be higher depending on quality of sequencing and genome annotation. Due to availability of genome and mRNA sequences genome-wide searches for sense-antisense transcripts have been reported, but few plant sense-antisense transcript pairs have been studied. Integration of these data in specialized databases is challenging problem of computer genomics. We have developed set of computer programs to define antisense transcripts and miRNA genes based on available sequencing data. We have analyzed data from PlantNATsDB (Plant Natural Antisense Transcripts DataBase which is a platform for annotating and discovering Natural Antisense Transcripts (NAT by integrating various data sources [1]. NATs can be grouped into two categories, cis-NATs and trans-NATs. Cis-NAT pairs are transcribed from opposing DNA strands at the same genomic locus and have a variety of orientations and differing lengths of overlap between the perfect sequence complementary regions, whereas trans-NAT pairs are transcribed from different loci and form partial complementarily. The database contains at the moment 69 plant species. The database provides an integrative, interactive and information-rich web graphical interface to

  15. GMATA: an integrated software package for genome-scale SSR mining, marker development and viewing

    Directory of Open Access Journals (Sweden)

    Xuewen Wang

    2016-09-01

    Full Text Available Simple sequence repeats (SSRs, also referred to as microsatellites, are highly variable tandem DNAs that are widely used as genetic markers. The increasing availability of whole-genome and transcript sequences provides information resources for SSR marker development. However, efficient software is required to efficiently identify and display SSR information along with other gene features at a genome scale. We developed novel software package Genome-wide Microsatellite Analyzing Tool Package (GMATA integrating SSR mining, statistical analysis and plotting, marker design, polymorphism screening and marker transferability, and enabled simultaneously display SSR markers with other genome features. GMATA applies novel strategies for SSR analysis and primer design in large genomes, which allows GMATA to perform faster calculation and provides more accurate results than existing tools. Our package is also capable of processing DNA sequences of any size on a standard computer. GMATA is user friendly, only requires mouse clicks or types inputs on the command line, and is executable in multiple computing platforms. We demonstrated the application of GMATA in plants genomes and reveal a novel distribution pattern of SSRs in 15 grass genomes. The most abundant motifs are dimer GA/TC, the A/T monomer and the GCG/CGC trimer, rather than the rich G/C content in DNA sequence. We also revealed that SSR count is a linear to the chromosome length in fully assembled grass genomes. GMATA represents a powerful application tool that facilitates genomic sequence analyses. GAMTA is freely available at http://sourceforge.net/projects/gmata/?source=navbar.

  16. GMATA: An Integrated Software Package for Genome-Scale SSR Mining, Marker Development and Viewing

    Science.gov (United States)

    Wang, Xuewen; Wang, Le

    2016-01-01

    Simple sequence repeats (SSRs), also referred to as microsatellites, are highly variable tandem DNAs that are widely used as genetic markers. The increasing availability of whole-genome and transcript sequences provides information resources for SSR marker development. However, efficient software is required to efficiently identify and display SSR information along with other gene features at a genome scale. We developed novel software package Genome-wide Microsatellite Analyzing Tool Package (GMATA) integrating SSR mining, statistical analysis and plotting, marker design, polymorphism screening and marker transferability, and enabled simultaneously display SSR markers with other genome features. GMATA applies novel strategies for SSR analysis and primer design in large genomes, which allows GMATA to perform faster calculation and provides more accurate results than existing tools. Our package is also capable of processing DNA sequences of any size on a standard computer. GMATA is user friendly, only requires mouse clicks or types inputs on the command line, and is executable in multiple computing platforms. We demonstrated the application of GMATA in plants genomes and reveal a novel distribution pattern of SSRs in 15 grass genomes. The most abundant motifs are dimer GA/TC, the A/T monomer and the GCG/CGC trimer, rather than the rich G/C content in DNA sequence. We also revealed that SSR count is a linear to the chromosome length in fully assembled grass genomes. GMATA represents a powerful application tool that facilitates genomic sequence analyses. GAMTA is freely available at http://sourceforge.net/projects/gmata/?source=navbar. PMID:27679641

  17. Integrating sequencing technologies in personal genomics: optimal low cost reconstruction of structural variants.

    Directory of Open Access Journals (Sweden)

    Jiang Du

    2009-07-01

    Full Text Available The goal of human genome re-sequencing is obtaining an accurate assembly of an individual's genome. Recently, there has been great excitement in the development of many technologies for this (e.g. medium and short read sequencing from companies such as 454 and SOLiD, and high-density oligo-arrays from Affymetrix and NimbelGen, with even more expected to appear. The costs and sensitivities of these technologies differ considerably from each other. As an important goal of personal genomics is to reduce the cost of re-sequencing to an affordable point, it is worthwhile to consider optimally integrating technologies. Here, we build a simulation toolbox that will help us optimally combine different technologies for genome re-sequencing, especially in reconstructing large structural variants (SVs. SV reconstruction is considered the most challenging step in human genome re-sequencing. (It is sometimes even harder than de novo assembly of small genomes because of the duplications and repetitive sequences in the human genome. To this end, we formulate canonical problems that are representative of issues in reconstruction and are of small enough scale to be computationally tractable and simulatable. Using semi-realistic simulations, we show how we can combine different technologies to optimally solve the assembly at low cost. With mapability maps, our simulations efficiently handle the inhomogeneous repeat-containing structure of the human genome and the computational complexity of practical assembly algorithms. They quantitatively show how combining different read lengths is more cost-effective than using one length, how an optimal mixed sequencing strategy for reconstructing large novel SVs usually also gives accurate detection of SNPs/indels, how paired-end reads can improve reconstruction efficiency, and how adding in arrays is more efficient than just sequencing for disentangling some complex SVs. Our strategy should facilitate the sequencing of

  18. Path-integral methods for analyzing the effects of fluctuations in stochastic hybrid neural networks.

    Science.gov (United States)

    Bressloff, Paul C

    2015-01-01

    We consider applications of path-integral methods to the analysis of a stochastic hybrid model representing a network of synaptically coupled spiking neuronal populations. The state of each local population is described in terms of two stochastic variables, a continuous synaptic variable and a discrete activity variable. The synaptic variables evolve according to piecewise-deterministic dynamics describing, at the population level, synapses driven by spiking activity. The dynamical equations for the synaptic currents are only valid between jumps in spiking activity, and the latter are described by a jump Markov process whose transition rates depend on the synaptic variables. We assume a separation of time scales between fast spiking dynamics with time constant [Formula: see text] and slower synaptic dynamics with time constant τ. This naturally introduces a small positive parameter [Formula: see text], which can be used to develop various asymptotic expansions of the corresponding path-integral representation of the stochastic dynamics. First, we derive a variational principle for maximum-likelihood paths of escape from a metastable state (large deviations in the small noise limit [Formula: see text]). We then show how the path integral provides an efficient method for obtaining a diffusion approximation of the hybrid system for small ϵ. The resulting Langevin equation can be used to analyze the effects of fluctuations within the basin of attraction of a metastable state, that is, ignoring the effects of large deviations. We illustrate this by using the Langevin approximation to analyze the effects of intrinsic noise on pattern formation in a spatially structured hybrid network. In particular, we show how noise enlarges the parameter regime over which patterns occur, in an analogous fashion to PDEs. Finally, we carry out a [Formula: see text]-loop expansion of the path integral, and use this to derive corrections to voltage-based mean-field equations, analogous

  19. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  20. Annotating novel genes by integrating synthetic lethals and genomic information

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou

    2008-01-01

    Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

  1. Integration of expression data in genome-scale metabolic network reconstructions

    Directory of Open Access Journals (Sweden)

    Anna S. Blazier

    2012-08-01

    Full Text Available With the advent of high-throughput technologies, the field of systems biology has amassed an abundance of omics data, quantifying thousands of cellular components across a variety of scales, ranging from mRNA transcript levels to metabolite quantities. Methods are needed to not only integrate this omics data but to also use this data to heighten the predictive capabilities of computational models. Several recent studies have successfully demonstrated how flux balance analysis (FBA, a constraint-based modeling approach, can be used to integrate transcriptomic data into genome-scale metabolic network reconstructions to generate predictive computational models. In this review, we summarize such FBA-based methods for integrating expression data into genome-scale metabolic network reconstructions, highlighting their advantages as well as their limitations.

  2. TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Jensen Paul A

    2011-09-01

    Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

  3. Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity.

    Science.gov (United States)

    Kirkman, Laura A; Lawrence, Elizabeth A; Deitsch, Kirk W

    2014-01-01

    Malaria parasites replicate asexually within their mammalian hosts as haploid cells and are subject to DNA damage from the immune response and chemotherapeutic agents that can significantly disrupt genomic integrity. Examination of the annotated genome of the parasite Plasmodium falciparum identified genes encoding core proteins required for the homologous recombination (HR) pathway for repairing DNA double-strand breaks (DSBs), but surprisingly none of the components of the canonical non-homologous end joining (C-NHEJ) pathway were identified. To better understand how malaria parasites repair DSBs and maintain genome integrity, we modified the yeast I-SceI endonuclease system to generate inducible, site-specific DSBs within the parasite's genome. Analysis of repaired genomic DNA showed that parasites possess both a typical HR pathway resulting in gene conversion events as well as an end joining (EJ) pathway for repair of DSBs when no homologous sequence is available. The products of EJ were limited in number and identical products were observed in multiple independent experiments. The repair junctions frequently contained short insertions also found in the surrounding sequences, suggesting the possibility of a templated repair process. We propose that an alternative end-joining pathway rather than C-NHEJ, serves as a primary method for repairing DSBs in malaria parasites.

  4. Evolution of endogenous non-retroviral genes integrated into plant genomes

    Directory of Open Access Journals (Sweden)

    Hyosub Chu

    2014-08-01

    Full Text Available Numerous comparative genome analyses have revealed the wide extent of horizontal gene transfer (HGT in living organisms, which contributes to their evolution and genetic diversity. Viruses play important roles in HGT. Endogenous viral elements (EVEs are defined as viral DNA sequences present within the genomes of non-viral organisms. In eukaryotic cells, the majority of EVEs are derived from RNA viruses using reverse transcription. In contrast, endogenous non-retroviral elements (ENREs are poorly studied. However, the increasing availability of genomic data and the rapid development of bioinformatics tools have enabled the identification of several ENREs in various eukaryotic organisms. To date, a small number of ENREs integrated into plant genomes have been identified. Of the known non-retroviruses, most identified ENREs are derived from double-strand (ds RNA viruses, followed by single-strand (ss DNA and ssRNA viruses. At least eight virus families have been identified. Of these, viruses in the family Partitiviridae are dominant, followed by viruses of the families Chrysoviridae and Geminiviridae. The identified ENREs have been primarily identified in eudicots, followed by monocots. In this review, we briefly discuss the current view on non-retroviral sequences integrated into plant genomes that are associated with plant-virus evolution and their possible roles in antiviral resistance.

  5. New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration.

    Science.gov (United States)

    Ambroset, Chloé; Coluzzi, Charles; Guédon, Gérard; Devignes, Marie-Dominique; Loux, Valentin; Lacroix, Thomas; Payot, Sophie; Leblond-Bourget, Nathalie

    2015-01-01

    Recent genome analyses suggest that integrative and conjugative elements (ICEs) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. However, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. Even though previous analysis showed the presence of ICEs in some species of Streptococci, the global prevalence and diversity of ICEs was not analyzed in this genus. In this study, we searched for ICEs in the completely sequenced genomes of 124 strains belonging to 27 streptococcal species. These exhaustive analyses revealed 105 putative ICEs and 26 slightly decayed elements whose limits were assessed and whose insertion site was identified. These ICEs were grouped in seven distinct unrelated or distantly related families, according to their conjugation modules. Integration of these streptococcal ICEs is catalyzed either by a site-specific tyrosine integrase, a low-specificity tyrosine integrase, a site-specific single serine integrase, a triplet of site-specific serine integrases or a DDE transposase. Analysis of their integration site led to the detection of 18 target-genes for streptococcal ICE insertion including eight that had not been identified previously (ftsK, guaA, lysS, mutT, rpmG, rpsI, traG, and ebfC). It also suggests that all specificities have evolved to minimize the impact of the insertion on the host. This overall analysis of streptococcal ICEs emphasizes their prevalence and diversity and demonstrates that exchanges or acquisitions of conjugation and recombination modules are frequent.

  6. Robust Integral of Neural Network and Error Sign Control of MIMO Nonlinear Systems.

    Science.gov (United States)

    Yang, Qinmin; Jagannathan, Sarangapani; Sun, Youxian

    2015-12-01

    This paper presents a novel state-feedback control scheme for the tracking control of a class of multi-input multioutput continuous-time nonlinear systems with unknown dynamics and bounded disturbances. First, the control law consisting of the robust integral of a neural network (NN) output plus sign of the tracking error feedback multiplied with an adaptive gain is introduced. The NN in the control law learns the system dynamics in an online manner, while the NN residual reconstruction errors and the bounded disturbances are overcome by the error sign signal. Since both of the NN output and the error sign signal are included in the integral, the continuity of the control input is ensured. The controller structure and the NN weight update law are novel in contrast with the previous effort, and the semiglobal asymptotic tracking performance is still guaranteed by using the Lyapunov analysis. In addition, the NN weights and all other signals are proved to be bounded simultaneously. The proposed approach also relaxes the need for the upper bounds of certain terms, which are usually required in the previous designs. Finally, the theoretical results are substantiated with simulations.

  7. Neural basis of limb ownership in individuals with body integrity identity disorder.

    Directory of Open Access Journals (Sweden)

    Milenna T van Dijk

    Full Text Available Our body feels like it is ours. However, individuals with body integrity identity disorder (BIID lack this feeling of ownership for distinct limbs and desire amputation of perfectly healthy body parts. This extremely rare condition provides us with an opportunity to study the neural basis underlying the feeling of limb ownership, since these individuals have a feeling of disownership for a limb in the absence of apparent brain damage. Here we directly compared brain activation between limbs that do and do not feel as part of the body using functional MRI during separate tactile stimulation and motor execution experiments. In comparison to matched controls, individuals with BIID showed heightened responsivity of a large somatosensory network including the parietal cortex and right insula during tactile stimulation, regardless of whether the stimulated leg felt owned or alienated. Importantly, activity in the ventral premotor cortex depended on the feeling of ownership and was reduced during stimulation of the alienated compared to the owned leg. In contrast, no significant differences between groups were observed during the performance of motor actions. These results suggest that altered somatosensory processing in the premotor cortex is associated with the feeling of disownership in BIID, which may be related to altered integration of somatosensory and proprioceptive information.

  8. The Neural Substrate and Functional Integration of Uncertainty in Decision Making: An Information Theory Approach

    Science.gov (United States)

    Goñi, Joaquín; Aznárez-Sanado, Maite; Arrondo, Gonzalo; Fernández-Seara, María; Loayza, Francis R.; Heukamp, Franz H.; Pastor, María A.

    2011-01-01

    Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm. PMID:21408065

  9. Neural Network Aided Kalman Filtering For Integrated GPS/INS Navigation System

    Directory of Open Access Journals (Sweden)

    Haidong GUO

    2013-01-01

    Full Text Available Kalman filter (KF uses measurement updates to correct system states error and to limit the errors in navigation solutions. However, only when the system dynamic and measurement models are correctly defined, and the noise statistics for the process are completely known, KF can optimally estimate a system’s states. Without measurement updates, Kalman filter’s prediction diverges; therefore the performance of an integrated GPS/INS navigation system may degrade rapidly when GPS signals are unavailable. This paper presents a neural network (NN aided Kalman filtering method to improve navigation solutions of integrated GPS/INS navigation system. In the proposed loosely coupled GPS/INS navigation system, extended KF (EKF estimates the INS measurement errors, plus position, velocity and attitude errors, and provides precise navigation solutions while GPS signals are available. At the same time, multi-layer NN is trained to map the vehicle manoeuvre with INS prediction errors during each GPS epoch, which is the input of the EKF. During GPS signal blockages, the NN can be used to predict the INS errors for EKF measurement updates, and in this way to improve navigation solutions. The principle of this hybrid method and the NN design are presented. Land vehicle based field test data are processed to evaluate the performance of the proposed method.

  10. Retrieval of dust storm aerosols using an integrated Neural Network model

    Science.gov (United States)

    Xiao, Fei; Wong, Man Sing; Lee, Kwon Ho; Campbell, James R.; Shea, Yu-kai

    2015-12-01

    Dust storms are known to have adverse effects on public health. Atmospheric dust loading is also one of the major uncertainties in global climatic modeling as it is known to have a significant impact on the radiation budget and atmospheric stability. This study develops an integrated model for dust storm detection and retrieval based on the combination of geostationary satellite images and forward trajectory model. The proposed model consists of three components: (i) a Neural Network (NN) model for near real-time detection of dust storms; (ii) a NN model for dust Aerosol Optical Thickness (AOT) retrieval; and (iii) the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model to analyze the transports of dust storms. These three components are combined using an event-driven active geo-processing workflow technique. The NN models were trained for the dust detection and validated using sunphotometer measurements from the AErosol RObotic NETwork (AERONET). The HYSPLIT model was applied in the regions with high probabilities of dust locations, and simulated the transport pathways of dust storms. This newly automated hybrid method can be used to give advance near real-time warning of dust storms, for both environmental authorities and public. The proposed methodology can be applied on early warning of adverse air quality conditions, and prediction of low visibility associated with dust storm events for port and airport authorities.

  11. Integration and Querying of Genomic and Proteomic Semantic Annotations for Biomedical Knowledge Extraction.

    Science.gov (United States)

    Masseroli, Marco; Canakoglu, Arif; Ceri, Stefano

    2016-01-01

    Understanding complex biological phenomena involves answering complex biomedical questions on multiple biomolecular information simultaneously, which are expressed through multiple genomic and proteomic semantic annotations scattered in many distributed and heterogeneous data sources; such heterogeneity and dispersion hamper the biologists' ability of asking global queries and performing global evaluations. To overcome this problem, we developed a software architecture to create and maintain a Genomic and Proteomic Knowledge Base (GPKB), which integrates several of the most relevant sources of such dispersed information (including Entrez Gene, UniProt, IntAct, Expasy Enzyme, GO, GOA, BioCyc, KEGG, Reactome, and OMIM). Our solution is general, as it uses a flexible, modular, and multilevel global data schema based on abstraction and generalization of integrated data features, and a set of automatic procedures for easing data integration and maintenance, also when the integrated data sources evolve in data content, structure, and number. These procedures also assure consistency, quality, and provenance tracking of all integrated data, and perform the semantic closure of the hierarchical relationships of the integrated biomedical ontologies. At http://www.bioinformatics.deib.polimi.it/GPKB/, a Web interface allows graphical easy composition of queries, although complex, on the knowledge base, supporting also semantic query expansion and comprehensive explorative search of the integrated data to better sustain biomedical knowledge extraction.

  12. IMG/M: integrated genome and metagenome comparative data analysis system.

    Science.gov (United States)

    Chen, I-Min A; Markowitz, Victor M; Chu, Ken; Palaniappan, Krishna; Szeto, Ernest; Pillay, Manoj; Ratner, Anna; Huang, Jinghua; Andersen, Evan; Huntemann, Marcel; Varghese, Neha; Hadjithomas, Michalis; Tennessen, Kristin; Nielsen, Torben; Ivanova, Natalia N; Kyrpides, Nikos C

    2017-01-04

    The Integrated Microbial Genomes with Microbiome Samples (IMG/M: https://img.jgi.doe.gov/m/) system contains annotated DNA and RNA sequence data of (i) archaeal, bacterial, eukaryotic and viral genomes from cultured organisms, (ii) single cell genomes (SCG) and genomes from metagenomes (GFM) from uncultured archaea, bacteria and viruses and (iii) metagenomes from environmental, host associated and engineered microbiome samples. Sequence data are generated by DOE's Joint Genome Institute (JGI), submitted by individual scientists, or collected from public sequence data archives. Structural and functional annotation is carried out by JGI's genome and metagenome annotation pipelines. A variety of analytical and visualization tools provide support for examining and comparing IMG/M's datasets. IMG/M allows open access interactive analysis of publicly available datasets, while manual curation, submission and access to private datasets and computationally intensive workspace-based analysis require login/password access to its expert review (ER) companion system (IMG/M ER: https://img.jgi.doe.gov/mer/). Since the last report published in the 2014 NAR Database Issue, IMG/M's dataset content has tripled in terms of number of datasets and overall protein coding genes, while its analysis tools have been extended to cope with the rapid growth in the number and size of datasets handled by the system.

  13. InterStoreDB: A Generic Integration Resource for Genetic and Genomic Data

    Institute of Scientific and Technical Information of China (English)

    Christopher G.Love; Ambrose E.Andongabo; Jun Wang; Pierre W.C.Carion; Christopher J.Rawlings; Graham J.King

    2012-01-01

    Associating phenotypic traits and quantitative trait loci (QTL) to causative regions of the underlying genome is a key goal in agricultural research.InterStoreDB is a suite of integrated databases designed to assist in this process.The individual databases are species independent and generic in design,providing access to curated datasets relating to plant populations,phenotypic traits,genetic maps,marker loci and QTL,with links to functional gene annotation and genomic sequence data.Each component database provides access to associated metadata,including data provenance and parameters used in analyses,thus providing users with information to evaluate the relative worth of any associations identified.The databases include CropStoreDB,for management of population,genetic map,QTL and trait measurement data,SeqStoreDB for sequence-related data and AlignStoreDB,which stores sequence alignment information,and allows navigation between genetic and genomic datasets.Genetic maps are visualized and compared using the CMAP tool,and functional annotation from sequenced genomes is provided via an EnsEMBL-based genome browser.This framework facilitates navigation of the multiple biological domains involved in genetics and genomics research in a transparent manner within a single portal.We demonstrate the value of InterStoreDB as a tool for Brassica research.InterStoreDB is available from:http:llwww.interstoredb.org

  14. Integrated and sequence-ordered BAC- and YAC-based physical maps for the rat genome.

    Science.gov (United States)

    Krzywinski, Martin; Wallis, John; Gösele, Claudia; Bosdet, Ian; Chiu, Readman; Graves, Tina; Hummel, Oliver; Layman, Dan; Mathewson, Carrie; Wye, Natasja; Zhu, Baoli; Albracht, Derek; Asano, Jennifer; Barber, Sarah; Brown-John, Mabel; Chan, Susanna; Chand, Steve; Cloutier, Alison; Davito, Jonathon; Fjell, Chris; Gaige, Tony; Ganten, Detlev; Girn, Noreen; Guggenheimer, Kurtis; Himmelbauer, Heinz; Kreitler, Thomas; Leach, Stephen; Lee, Darlene; Lehrach, Hans; Mayo, Michael; Mead, Kelly; Olson, Teika; Pandoh, Pawan; Prabhu, Anna-Liisa; Shin, Heesun; Tänzer, Simone; Thompson, Jason; Tsai, Miranda; Walker, Jason; Yang, George; Sekhon, Mandeep; Hillier, LaDeana; Zimdahl, Heike; Marziali, Andre; Osoegawa, Kazutoyo; Zhao, Shaying; Siddiqui, Asim; de Jong, Pieter J; Warren, Wes; Mardis, Elaine; McPherson, John D; Wilson, Richard; Hübner, Norbert; Jones, Steven; Marra, Marco; Schein, Jacqueline

    2004-04-01

    As part of the effort to sequence the genome of Rattus norvegicus, we constructed a physical map comprised of fingerprinted bacterial artificial chromosome (BAC) clones from the CHORI-230 BAC library. These BAC clones provide approximately 13-fold redundant coverage of the genome and have been assembled into 376 fingerprint contigs. A yeast artificial chromosome (YAC) map was also constructed and aligned with the BAC map via fingerprinted BAC and P1 artificial chromosome clones (PACs) sharing interspersed repetitive sequence markers with the YAC-based physical map. We have annotated 95% of the fingerprint map clones in contigs with coordinates on the version 3.1 rat genome sequence assembly, using BAC-end sequences and in silico mapping methods. These coordinates have allowed anchoring 358 of the 376 fingerprint map contigs onto the sequence assembly. Of these, 324 contigs are anchored to rat genome sequences localized to chromosomes, and 34 contigs are anchored to unlocalized portions of the rat sequence assembly. The remaining 18 contigs, containing 54 clones, still require placement. The fingerprint map is a high-resolution integrative data resource that provides genome-ordered associations among BAC, YAC, and PAC clones and the assembled sequence of the rat genome.

  15. Ensembl Plants: Integrating Tools for Visualizing, Mining, and Analyzing Plant Genomics Data.

    Science.gov (United States)

    Bolser, Dan; Staines, Daniel M; Pritchard, Emily; Kersey, Paul

    2016-01-01

    Ensembl Plants ( http://plants.ensembl.org ) is an integrative resource presenting genome-scale information for a growing number of sequenced plant species (currently 33). Data provided includes genome sequence, gene models, functional annotation, and polymorphic loci. Various additional information are provided for variation data, including population structure, individual genotypes, linkage, and phenotype data. In each release, comparative analyses are performed on whole genome and protein sequences, and genome alignments and gene trees are made available that show the implied evolutionary history of each gene family. Access to the data is provided through a genome browser incorporating many specialist interfaces for different data types, and through a variety of additional methods for programmatic access and data mining. These access routes are consistent with those offered through the Ensembl interface for the genomes of non-plant species, including those of plant pathogens, pests, and pollinators.Ensembl Plants is updated 4-5 times a year and is developed in collaboration with our international partners in the Gramene ( http://www.gramene.org ) and transPLANT projects ( http://www.transplantdb.org ).

  16. Molecular verification of the integration of Tripsacum dactyloides DNA into wheat genome through wide hybridization

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    RAPD and RFLP analyses of double haploid lines which derived from hybridization between hexaploid wheat (Triticum aestivum L.2n=42) and eastern gamagrass (Tripsacum dactyloides L.2n=4x=72) are reported.Two of the 340 Operon primers have been screened,which stably amplified Tripsacum dactyloides (male parent) specific bands in the double haploid lines.These results confirm the fact that Tripsacum dactyloides DNA has been integrated into wheat genome by sexual hybridization at molecular level.This idea has been further testified by RFLP analysis.Application and potentials of transferring Tripsacum dactyloides DNA into wheat genome by sexual hybridization in wheat breeding are discussed.

  17. Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate

    Directory of Open Access Journals (Sweden)

    Priya Srikanth

    2015-09-01

    Full Text Available Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1 as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11 translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

  18. Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson's Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations.

    Science.gov (United States)

    Momcilovic, Olga; Sivapatham, Renuka; Oron, Tal Ronnen; Meyer, Morten; Mooney, Sean; Rao, Mahendra S; Zeng, Xianmin

    2016-01-01

    We report generation of induced pluripotent stem cell (iPSC) lines from ten Parkinson's disease (PD) patients carrying SNCA, PARK2, LRRK2, and GBA mutations, and one age-matched control. After validation of pluripotency, long-term genome stability, and integration-free reprogramming, eight of these lines (one of each SNCA, LRRK2 and GBA, four PARK2 lines, and the control) were differentiated into neural stem cells (NSC) and subsequently to dopaminergic cultures. We did not observe significant differences in the timeline of neural induction and NSC derivation between the patient and control line, nor amongst the patient lines, although we report considerable variability in the efficiency of dopaminergic differentiation among patient lines. We performed whole genome expression analyses of the lines at each stage of differentiation (fibroblast, iPSC, NSC, and dopaminergic culture) in an attempt to identify alterations by large-scale evaluation. While gene expression profiling clearly distinguished cells at different stages of differentiation, no mutation-specific clustering or difference was observed, though consistent changes in patient lines were detected in genes associated mitochondrial biology. We further examined gene expression in a stress model (MPTP-induced dopaminergic neuronal death) using two clones from the SNCA triplication line, and detected changes in genes associated with mitophagy. Our data suggested that even a well-characterized line of a monogenic disease may not be sufficient to determine the cause or mechanism of the disease, and highlights the need to use more focused strategies for large-scale data analysis.

  19. Genomic analysis of Sleeping Beauty transposon integration in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Giandomenico Turchiano

    Full Text Available The Sleeping Beauty (SB transposon is a non-viral integrating vector system with proven efficacy for gene transfer and functional genomics. However, integration efficiency is negatively affected by the length of the transposon. To optimize the SB transposon machinery, the inverted repeats and the transposase gene underwent several modifications, resulting in the generation of the hyperactive SB100X transposase and of the high-capacity "sandwich" (SA transposon. In this study, we report a side-by-side comparison of the SA and the widely used T2 arrangement of transposon vectors carrying increasing DNA cargoes, up to 18 kb. Clonal analysis of SA integrants in human epithelial cells and in immortalized keratinocytes demonstrates stability and integrity of the transposon independently from the cargo size and copy number-dependent expression of the cargo cassette. A genome-wide analysis of unambiguously mapped SA integrations in keratinocytes showed an almost random distribution, with an overrepresentation in repetitive elements (satellite, LINE and small RNAs compared to a library representing insertions of the first-generation transposon vector and to gammaretroviral and lentiviral libraries. The SA transposon/SB100X integrating system therefore shows important features as a system for delivering large gene constructs for gene therapy applications.

  20. Genomic analysis of Sleeping Beauty transposon integration in human somatic cells.

    Science.gov (United States)

    Turchiano, Giandomenico; Latella, Maria Carmela; Gogol-Döring, Andreas; Cattoglio, Claudia; Mavilio, Fulvio; Izsvák, Zsuzsanna; Ivics, Zoltán; Recchia, Alessandra

    2014-01-01

    The Sleeping Beauty (SB) transposon is a non-viral integrating vector system with proven efficacy for gene transfer and functional genomics. However, integration efficiency is negatively affected by the length of the transposon. To optimize the SB transposon machinery, the inverted repeats and the transposase gene underwent several modifications, resulting in the generation of the hyperactive SB100X transposase and of the high-capacity "sandwich" (SA) transposon. In this study, we report a side-by-side comparison of the SA and the widely used T2 arrangement of transposon vectors carrying increasing DNA cargoes, up to 18 kb. Clonal analysis of SA integrants in human epithelial cells and in immortalized keratinocytes demonstrates stability and integrity of the transposon independently from the cargo size and copy number-dependent expression of the cargo cassette. A genome-wide analysis of unambiguously mapped SA integrations in keratinocytes showed an almost random distribution, with an overrepresentation in repetitive elements (satellite, LINE and small RNAs) compared to a library representing insertions of the first-generation transposon vector and to gammaretroviral and lentiviral libraries. The SA transposon/SB100X integrating system therefore shows important features as a system for delivering large gene constructs for gene therapy applications.

  1. Integrating geomorphic and habitat assessments to classify streams using artificial neural networks

    Science.gov (United States)

    Fytilis, N.; Mathon, B. R.; Rizzo, D. M.; Stevens, L.; Morrissey, L. A.

    2009-12-01

    Environmental managers are increasingly required to forecast long-term effects and/or the resilience and vulnerability of biophysical systems to human-generated stresses. We research and develop a classification tool to be used by decision-makers to identify how channel, floodplain and watershed scale stressors affect hydrological processes and in doing so, alter the physical structure and habitat values of streams. In the development of this work, we are using the rapid geomorphic assessment protocols (RGA), as well as, the rapid habitat assessment protocols (RHA) from over 800 Vermont stream reaches assessed by the Vermont Agency of Natural Resources (VTANR). We extend previous work focused on RGA to include RHA because natural communities are directly and/or indirectly affected by land use history, stream geomorphology and disturbance regime history. Our approach integrates spatial statistics with artificial neural networks (ANNs) visualized in GIS to examine the effect of land use and geomorphology on biodiversity. A specific data-driven ANN, known as a counterpropagation neural network originally developed by Hecht-Nielsen [1987] will be used to: (1) provide a standardized, expert-trained approach for classifying the sensitivity of river networks in various contexts (erosion hazard mitigation, habitat restoration and conservation) and (2) document the weights experts place on various parameters when classifying stream geomorphic condition, inherent vulnerability, and overall sensitivity at the reach-scale. The procedure is data-driven, and therefore does not require the development of site-specific, process-based stream models, or sets of if-then-else rules associated with expert systems. The ANN architecture is sufficiently flexible to allow for its continual update and refinement in light of new and expanded understandings of fluvial geomorphology. This has potential to save time and resources, while enabling a truly adaptive management approach using expert

  2. A Novel Fractional-Order PID Controller for Integrated Pressurized Water Reactor Based on Wavelet Kernel Neural Network Algorithm

    Directory of Open Access Journals (Sweden)

    Yu-xin Zhao

    2014-01-01

    Full Text Available This paper presents a novel wavelet kernel neural network (WKNN with wavelet kernel function. It is applicable in online learning with adaptive parameters and is applied on parameters tuning of fractional-order PID (FOPID controller, which could handle time delay problem of the complex control system. Combining the wavelet function and the kernel function, the wavelet kernel function is adopted and validated the availability for neural network. Compared to the conservative wavelet neural network, the most innovative character of the WKNN is its rapid convergence and high precision in parameters updating process. Furthermore, the integrated pressurized water reactor (IPWR system is established by RELAP5, and a novel control strategy combining WKNN and fuzzy logic rule is proposed for shortening controlling time and utilizing the experiential knowledge sufficiently. Finally, experiment results verify that the control strategy and controller proposed have the practicability and reliability in actual complicated system.

  3. Integrating multiple genome annotation databases improves the interpretation of microarray gene expression data

    Directory of Open Access Journals (Sweden)

    Kennedy Breandan

    2010-01-01

    Full Text Available Abstract Background The Affymetrix GeneChip is a widely used gene expression profiling platform. Since the chips were originally designed, the genome databases and gene definitions have been considerably updated. Thus, more accurate interpretation of microarray data requires parallel updating of the specificity of GeneChip probes. We propose a new probe remapping protocol, using the zebrafish GeneChips as an example, by removing nonspecific probes, and grouping the probes into transcript level probe sets using an integrated zebrafish genome annotation. This genome annotation is based on combining transcript information from multiple databases. This new remapping protocol, especially the new genome annotation, is shown here to be an important factor in improving the interpretation of gene expression microarray data. Results Transcript data from the RefSeq, GenBank and Ensembl databases were downloaded from the UCSC genome browser, and integrated to generate a combined zebrafish genome annotation. Affymetrix probes were filtered and remapped according to the new annotation. The influence of transcript collection and gene definition methods was tested using two microarray data sets. Compared to remapping using a single database, this new remapping protocol results in up to 20% more probes being retained in the remapping, leading to approximately 1,000 more genes being detected. The differentially expressed gene lists are consequently increased by up to 30%. We are also able to detect up to three times more alternative splicing events. A small number of the bioinformatics predictions were confirmed using real-time PCR validation. Conclusions By combining gene definitions from multiple databases, it is possible to greatly increase the numbers of genes and splice variants that can be detected in microarray gene expression experiments.

  4. An integrative genomic approach to uncover molecular mechanisms of prokaryotic traits.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2006-11-01

    Full Text Available With mounting availability of genomic and phenotypic databases, data integration and mining become increasingly challenging. While efforts have been put forward to analyze prokaryotic phenotypes, current computational technologies either lack high throughput capacity for genomic scale analysis, or are limited in their capability to integrate and mine data across different scales of biology. Consequently, simultaneous analysis of associations among genomes, phenotypes, and gene functions is prohibited. Here, we developed a high throughput computational approach, and demonstrated for the first time the feasibility of integrating large quantities of prokaryotic phenotypes along with genomic datasets for mining across multiple scales of biology (protein domains, pathways, molecular functions, and cellular processes. Applying this method over 59 fully sequenced prokaryotic species, we identified genetic basis and molecular mechanisms underlying the phenotypes in bacteria. We identified 3,711 significant correlations between 1,499 distinct Pfam and 63 phenotypes, with 2,650 correlations and 1,061 anti-correlations. Manual evaluation of a random sample of these significant correlations showed a minimal precision of 30% (95% confidence interval: 20%-42%; n = 50. We stratified the most significant 478 predictions and subjected 100 to manual evaluation, of which 60 were corroborated in the literature. We furthermore unveiled 10 significant correlations between phenotypes and KEGG pathways, eight of which were corroborated in the evaluation, and 309 significant correlations between phenotypes and 166 GO concepts evaluated using a random sample (minimal precision = 72%; 95% confidence interval: 60%-80%; n = 50. Additionally, we conducted a novel large-scale phenomic visualization analysis to provide insight into the modular nature of common molecular mechanisms spanning multiple biological scales and reused by related phenotypes (metaphenotypes. We propose

  5. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Science.gov (United States)

    Ali Hassan, Nur Zarina; Mokhtar, Norfilza Mohd; Kok Sin, Teow; Mohamed Rose, Isa; Sagap, Ismail; Harun, Roslan; Jamal, Rahman

    2014-01-01

    Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV) and gene expression in colorectal cancer (CRC) samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  6. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Directory of Open Access Journals (Sweden)

    Nur Zarina Ali Hassan

    Full Text Available Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV and gene expression in colorectal cancer (CRC samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  7. Multi-omic data integration and analysis using systems genomics approaches

    DEFF Research Database (Denmark)

    Suravajhala, Prashanth; Kogelman, Lisette; Kadarmideen, Haja

    2016-01-01

    , health and welfare. We conclude that there are big challenges in multi-omic data integration, modelling and systems-level analyses, particularly with the fast emerging HTO technologies. We highlight existing and emerging systems genomics approaches and discuss how they contribute to our understanding...... on animal production and health traits. However, notwithstanding these new HTO technologies, there remains an emerging challenge in data analysis. On the one hand, different HTO technologies judged on their own merit are appropriate for the identification of disease-causing genes, biomarkers for prevention...... and drug targets for the treatment of diseases and for individualized genomic predictions of performance or disease risks. On the other hand, integration of multi-omic data and joint modelling and analyses are very powerful and accurate to understand the systems biology of healthy and sustainable...

  8. Detection of integrated herpesvirus genomes by fluorescence in situ hybridization (FISH).

    Science.gov (United States)

    Kaufer, Benedikt B

    2013-01-01

    Fluorescence in situ hybridization (FISH) is widely used to visualize nucleotide sequences in interphase cells or on metaphase chromosomes using specific probes that are complementary to the respective targets. Besides its broad application in cytogenetics and cancer research, FISH facilitates the localization of virus genomes in infected cells. Some herpesviruses, including human herpesvirus 6 (HHV-6) and Marek's disease virus (MDV), have been shown to integrate their genetic material into host chromosomes, which allows transmission of HHV-6 via the germ line and is required for efficient MDV-induced tumor formation. We describe here the detection by FISH of integrated herpesvirus genomes in metaphase chromosomes and interphase nuclei of herpesvirus-infected cells.

  9. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    Science.gov (United States)

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  10. RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

    Energy Technology Data Exchange (ETDEWEB)

    Novichkov, Pavel S.; Rodionov, Dmitry A.; Stavrovskaya, Elena D.; Novichkova, Elena S.; Kazakov, Alexey E.; Gelfand, Mikhail S.; Arkin, Adam P.; Mironov, Andrey A.; Dubchak, Inna

    2010-05-26

    RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov.

  11. Solutions for data integration in functional genomics: a critical assessment and case study.

    Science.gov (United States)

    Smedley, Damian; Swertz, Morris A; Wolstencroft, Katy; Proctor, Glenn; Zouberakis, Michael; Bard, Jonathan; Hancock, John M; Schofield, Paul

    2008-11-01

    The torrent of data emerging from the application of new technologies to functional genomics and systems biology can no longer be contained within the traditional modes of data sharing and publication with the consequence that data is being deposited in, distributed across and disseminated through an increasing number of databases. The resulting fragmentation poses serious problems for the model organism community which increasingly rely on data mining and computational approaches that require gathering of data from a range of sources. In the light of these problems, the European Commission has funded a coordination action, CASIMIR (coordination and sustainability of international mouse informatics resources), with a remit to assess the technical and social aspects of database interoperability that currently prevent the full realization of the potential of data integration in mouse functional genomics. In this article, we assess the current problems with interoperability, with particular reference to mouse functional genomics, and critically review the technologies that can be deployed to overcome them. We describe a typical use-case where an investigator wishes to gather data on variation, genomic context and metabolic pathway involvement for genes discovered in a genome-wide screen. We go on to develop an automated approach involving an in silico experimental workflow tool, Taverna, using web services, BioMart and MOLGENIS technologies for data retrieval. Finally, we focus on the current impediments to adopting such an approach in a wider context, and strategies to overcome them.

  12. Global transcript structure resolution of high gene density genomes through multi-platform data integration.

    Science.gov (United States)

    O'Grady, Tina; Wang, Xia; Höner Zu Bentrup, Kerstin; Baddoo, Melody; Concha, Monica; Flemington, Erik K

    2016-10-14

    Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity than is captured by existing annotation. The pervasive nature of overlapping transcription throughout herpesvirus genomes, however, poses substantial problems in resolving transcript structures using these methods alone. We present an approach that combines the unique attributes of Pacific Biosciences Iso-Seq long-read, Illumina short-read and deepCAGE (Cap Analysis of Gene Expression) sequencing to globally resolve polyadenylated isoform structures in replicating Epstein-Barr virus (EBV). Our method, Transcriptome Resolution through Integration of Multi-platform Data (TRIMD), identifies nearly 300 novel EBV transcripts, quadrupling the size of the annotated viral transcriptome. These findings illustrate an array of mechanisms through which EBV achieves functional diversity in its relatively small, compact genome including programmed alternative splicing (e.g. across the IR1 repeats), alternative promoter usage by LMP2 and other latency-associated transcripts, intergenic splicing at the BZLF2 locus, and antisense transcription and pervasive readthrough transcription throughout the genome.

  13. BiGG Models: A platform for integrating, standardizing and sharing genome-scale models.

    Science.gov (United States)

    King, Zachary A; Lu, Justin; Dräger, Andreas; Miller, Philip; Federowicz, Stephen; Lerman, Joshua A; Ebrahim, Ali; Palsson, Bernhard O; Lewis, Nathan E

    2016-01-01

    Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories of high-quality models must be established, models must adhere to established standards and model components must be linked to relevant databases. Tools for model visualization further enhance their utility. To meet these needs, we present BiGG Models (http://bigg.ucsd.edu), a completely redesigned Biochemical, Genetic and Genomic knowledge base. BiGG Models contains more than 75 high-quality, manually-curated genome-scale metabolic models. On the website, users can browse, search and visualize models. BiGG Models connects genome-scale models to genome annotations and external databases. Reaction and metabolite identifiers have been standardized across models to conform to community standards and enable rapid comparison across models. Furthermore, BiGG Models provides a comprehensive application programming interface for accessing BiGG Models with modeling and analysis tools. As a resource for highly curated, standardized and accessible models of metabolism, BiGG Models will facilitate diverse systems biology studies and support knowledge-based analysis of diverse experimental data.

  14. Integration of Novel Materials and Advanced Genomic Technologies into New Vaccine Design.

    Science.gov (United States)

    Liao, Wenzhen; Zhang, Tian-Tian; Gao, Liqian; Lee, Su Seong; Xu, Jie; Zhang, Han; Yang, Zhaogang; Liu, Zhaoyu; Li, Wen

    2017-01-01

    Designing new vaccines is one of the most challenging tasks for public health to prevent both infectious and chronic diseases. Even though many research scientists have spent great efforts in improving the specificity, sensitivity and safety of current available vaccines, there are still much space on how to effectively combine different biomaterials and technologies to design universal or personalized vaccines. Traditionally, vaccines were made based on empirical approaches designed to mimic immunity induced by natural infection. Either live attenuated or killed whole microorganisms were used as vaccines. With the development of biomaterial science, DNA/RNA, recombinant vector, adjuvant and nanoparticles greatly expand the category of vaccines. More importantly, with the tremendous advances of new technologies including genomics, proteomics and immunomics, the paradigm of vaccine design has shifted from microbiological to sequence-based approaches. This ever-growing large amount of genomic data and new genomic approaches such as comparative genomics, reverse vaccinology and pan-genomics, will play critical roles in novel vaccine design and enable development of more effective vaccines to cure and control both chronic and infectious diseases. In this review, we summarize current various vaccine materials, advanced technologies and combinational strategies to integrate biomaterials and advanced technologies for vaccine design, which we hope will provide some very useful guidelines and perspectives for the vaccine design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Proteomics and integrative genomics for unraveling the mysteries of spermatogenesis: the strategies of a team.

    Science.gov (United States)

    Com, Emmanuelle; Melaine, Nathalie; Chalmel, Frédéric; Pineau, Charles

    2014-07-31

    The strikingly complex structural organization of the mammalian testis in vivo creates particular difficulties for studies of its organization, function and regulation. These difficulties are particularly pronounced for investigations of the molecular communication networks within the seminiferous tubules that govern spermatogenesis. The use of classical molecular and cell biology approaches to unravel this complexity has proved problematic, due to difficulties in maintaining differentiated germ cells in vitro, in particular. The lack of a suitable testing ground has led to a greater reliance on high-quality proteomic and genomic analyses as a prelude to the in vitro antx1d in vivo testing of hypotheses. In this study, we highlight the options currently available for research, as used in our laboratory, in which proteomic and integrative genomic strategies are applied to the study of spermatogenesis in mammals. We will comment on results providing insight into the molecular mechanisms underlying normal and pathological spermatogenesis and new perspectives for the treatment of male infertility in humans. Finally, we will discuss the relevance of our strategies and the unexpected potential and perspectives they offer to teams involved in the study of male reproduction, within the framework of the Human Proteome Project. Integrative genomics is becoming a powerful strategy for discovering the biological significance hidden in proteomic datasets. This work introduces some of the integrative genomic concepts and works used by our team to gain new insight into mammalian spermatogenesis, a remarkably sophisticated process. We demonstrate the relevance of these integrative approaches to understand the cellular cross talks established between the somatic Sertoli cells and the germ cell lineage, within the seminiferous epithelium. Our work also contributes to new knowledge on the pathophysiology of testicular function, with promising clinical applications. This article is

  16. Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels

    Science.gov (United States)

    Liu, Bin; Kim, Eric; Meggo, Anika; Gandhi, Sachin; Luo, Hao; Kallakuri, Srinivas; Xu, Yong; Zhang, Jinsheng

    2017-04-01

    Objective. Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. Approach. We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. Main results. The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. Significance. The new design will help enhance the long-term stability of the implantable devices.

  17. Generation of Integration-free and Region-Specific Neural Progenitors from Primate Fibroblasts

    Directory of Open Access Journals (Sweden)

    Jianfeng Lu

    2013-05-01

    Full Text Available Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF, transforming growth factor (TGF-β inhibitor SB431542, and glycogen synthase kinase (GSK-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC colonies formed at either 37°C or 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development.

  18. A Combination of Wavelet Artificial Neural Networks Integrated with Bootstrap Sampler in Time Series Prediction

    Directory of Open Access Journals (Sweden)

    Tásia Hickmann

    2015-11-01

    Full Text Available In this paper, an iterative forecasting methodology for time series prediction that integrates wavelet de-noising and decomposition with an Artificial Neural Network (ANN and Bootstrap methods is put forward here. Basically, a given time series to be forecasted is initially decomposed into trend and noise (wavelet components by using a wavelet de-noising algorithm. Both trend and noise components are then further decomposed by means of a wavelet decomposition method producing orthonormal Wavelet Components (WCs for each one. Each WC is separately modelled through an ANN in order to provide both in-sample and out-of-sample forecasts. At each time t, the respective forecasts of the WCs of the trend and noise components are simply added to produce the in-sample and out-of-sample forecasts of the underlying time series. Finally, out-of-sample predictive densities are empirically simulated by the Bootstrap sampler and the confidence intervals are then yielded, considering some level of credibility. The proposed methodology, when applied to the well-known Canadian lynx data that exhibit non-linearity and non-Gaussian properties, has outperformed other methods traditionally used to forecast it.

  19. Optimal sensorimotor integration in recurrent cortical networks: a neural implementation of Kalman filters.

    Science.gov (United States)

    Denève, Sophie; Duhamel, Jean-René; Pouget, Alexandre

    2007-05-23

    Several behavioral experiments suggest that the nervous system uses an internal model of the dynamics of the body to implement a close approximation to a Kalman filter. This filter can be used to perform a variety of tasks nearly optimally, such as predicting the sensory consequence of motor action, integrating sensory and body posture signals, and computing motor commands. We propose that the neural implementation of this Kalman filter involves recurrent basis function networks with attractor dynamics, a kind of architecture that can be readily mapped onto cortical circuits. In such networks, the tuning curves to variables such as arm velocity are remarkably noninvariant in the sense that the amplitude and width of the tuning curves of a given neuron can vary greatly depending on other variables such as the position of the arm or the reliability of the sensory feedback. This property could explain some puzzling properties of tuning curves in the motor and premotor cortex, and it leads to several new predictions.

  20. The future of genome-scale modeling of yeast through integration of a transcriptional regulatory network

    DEFF Research Database (Denmark)

    Liu, Guodong; Marras, Antonio; Nielsen, Jens

    2014-01-01

    regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network (TRN) for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model......Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional...... transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner....

  1. Genome-wide analysis reveals the extent of EAV-HP integration in domestic chicken

    OpenAIRE

    Wragg, David; Mason, Andrew S.; Yu, Le; Kuo, Richard; Lawal, Raman A.; Desta, Takele Taye; Mwacharo, Joram M.; Cho, Chang-Yeon; Kemp, Stephen; Burt, David W; Hanotte, Olivier

    2015-01-01

    BACKGROUND: EAV-HP is an ancient retrovirus pre-dating Gallus speciation, which continues to circulate in modern chicken populations, and led to the emergence of avian leukosis virus subgroup J causing significant economic losses to the poultry industry. We mapped EAV-HP integration sites in Ethiopian village chickens, a Silkie, Taiwan Country chicken, red junglefowl Gallus gallus and several inbred experimental lines using whole-genome sequence data.RESULTS: An average of 75.22 ± 9.52 integr...

  2. Role of the short telomeric repeat region in Marek's disease virus replication, genomic integration, and lymphomagenesis.

    Science.gov (United States)

    Greco, Annachiara; Fester, Nadine; Engel, Annemarie T; Kaufer, Benedikt B

    2014-12-01

    Marek's disease virus (MDV) is a cell-associated alphaherpesvirus that causes generalized polyneuritis and T-cell lymphomas in chickens. MDV is able to integrate its genome into host telomeres, but the mechanism of integration is poorly understood. The MDV genome harbors two arrays of telomeric repeats (TMR) at the ends of its linear genome: multiple telomeric repeats (mTMR), with a variable number of up to 100 repeats, and short telomeric repeats (sTMR), with a fixed number of 6 repeats. The mTMR have recently been shown to play an important role in MDV integration and tumor formation; however, the functions of the sTMR have remained unknown. In this study, we demonstrate that deletion of the sTMR in the MDV genome abrogates virus replication, while extensive mutation of the sTMR does not, indicating that the presence of the sTMR but not the sTMR sequence itself is important. Furthermore, we generated a panel of truncation mutants to determine the minimal length of the sTMR and observed a direct correlation between sTMR length and MDV replication. To address the role of sTMR in MDV replication, integration, and tumorigenesis, sTMR sequences were replaced by a scrambled repeated sequence (vsTMR_mut). vsTMR_mut replicated comparably to parental and revertant viruses in vitro. In vivo, however, a significant reduction in disease and tumor incidence was observed in chickens infected with vsTMR_mut that also correlated with a reduced number of viral integration sites in tumor cells. Taken together, our data demonstrate that the sTMR play a central role in MDV genome replication, pathogenesis, and MDV-induced tumor formation. Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes high economic losses in the poultry industry. MDV integrates its genetic material into host telomeres, a process that is crucial for efficient tumor formation. The MDV genome harbors two arrays of telomeric repeats (TMR) at the ends of its linear

  3. MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells

    Institute of Scientific and Technical Information of China (English)

    Jing Xu; Xiaojuan Sun; Yudong Jing; Mo Wang; Kai Liu; Youli Jian; Mei Yang; Zhukuan Cheng; Chonglin Yang

    2012-01-01

    During meiotic cell division,proper chromosome synapsis and accurate repair of DNA double strand breaks (DSBs) are required to maintain genomic integrity,loss of which leads to apoptosis or meiotic defects.The mechanisms underlying meiotic chromosome synapsis,DSB repair and apoptosis are not fully understood.Here,we report that the chromodomain-containiug protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans.Loss ofmrg-1 function resulted in a significant increase in germ cell apoptosis that was partially inhibited by mutations affecting DNA damage checkpoint genes.Consistently,mrg-1 mutant germ lines exhibited SPO-11-generated DSBs and elevated exogenous DNA damage-induced chromosome fragmentation at diakinesis.In addition,the excessive apoptosis in mrg-1 mutants was partially suppressed by loss of the synapsis checkpoint gene pch-2,and a significant number of meiotic nuclei accumulated at the leptotene/zygotene stages with an elevated level of H3K9me2 on the chromatin,which was similarly observed in mutants deficient in the synaptonemal complex,suggesting that the proper progression of chromosome synapsis is likely impaired in the absence of mrg-1.Altogether,these findings suggest that MRG-1 is critical for genomic integrity by promoting meiotic DSB repair and synapsis progression in meiosis.

  4. Matching of array CGH and gene expression microarray features for the purpose of integrative genomic analyses

    Directory of Open Access Journals (Sweden)

    van Wieringen Wessel N

    2012-05-01

    Full Text Available Abstract Background An increasing number of genomic studies interrogating more than one molecular level is published. Bioinformatics follows biological practice, and recent years have seen a surge in methodology for the integrative analysis of genomic data. Often such analyses require knowledge of which elements of one platform link to those of another. Although important, many integrative analyses do not or insufficiently detail the matching of the platforms. Results We describe, illustrate and discuss six matching procedures. They are implemented in the R-package sigaR (available from Bioconductor. The principles underlying the presented matching procedures are generic, and can be combined to form new matching approaches or be applied to the matching of other platforms. Illustration of the matching procedures on a variety of data sets reveals how the procedures differ in the use of the available data, and may even lead to different results for individual genes. Conclusions Matching of data from multiple genomics platforms is an important preprocessing step for many integrative bioinformatic analysis, for which we present six generic procedures, both old and new. They have been implemented in the R-package sigaR, available from Bioconductor.

  5. CTDB: An Integrated Chickpea Transcriptome Database for Functional and Applied Genomics.

    Directory of Open Access Journals (Sweden)

    Mohit Verma

    Full Text Available Chickpea is an important grain legume used as a rich source of protein in human diet. The narrow genetic diversity and limited availability of genomic resources are the major constraints in implementing breeding strategies and biotechnological interventions for genetic enhancement of chickpea. We developed an integrated Chickpea Transcriptome Database (CTDB, which provides the comprehensive web interface for visualization and easy retrieval of transcriptome data in chickpea. The database features many tools for similarity search, functional annotation (putative function, PFAM domain and gene ontology search and comparative gene expression analysis. The current release of CTDB (v2.0 hosts transcriptome datasets with high quality functional annotation from cultivated (desi and kabuli types and wild chickpea. A catalog of transcription factor families and their expression profiles in chickpea are available in the database. The gene expression data have been integrated to study the expression profiles of chickpea transcripts in major tissues/organs and various stages of flower development. The utilities, such as similarity search, ortholog identification and comparative gene expression have also been implemented in the database to facilitate comparative genomic studies among different legumes and Arabidopsis. Furthermore, the CTDB represents a resource for the discovery of functional molecular markers (microsatellites and single nucleotide polymorphisms between different chickpea types. We anticipate that integrated information content of this database will accelerate the functional and applied genomic research for improvement of chickpea. The CTDB web service is freely available at http://nipgr.res.in/ctdb.html.

  6. A Neural Dynamic Architecture for Reaching and Grasping Integrates Perception and Movement Generation and Enables On-Line Updating

    Science.gov (United States)

    Knips, Guido; Zibner, Stephan K. U.; Reimann, Hendrik; Schöner, Gregor

    2017-01-01

    Reaching for objects and grasping them is a fundamental skill for any autonomous robot that interacts with its environment. Although this skill seems trivial to adults, who effortlessly pick up even objects they have never seen before, it is hard for other animals, for human infants, and for most autonomous robots. Any time during movement preparation and execution, human reaching movement are updated if the visual scene changes (with a delay of about 100 ms). The capability for online updating highlights how tightly perception, movement planning, and movement generation are integrated in humans. Here, we report on an effort to reproduce this tight integration in a neural dynamic process model of reaching and grasping that covers the complete path from visual perception to movement generation within a unified modeling framework, Dynamic Field Theory. All requisite processes are realized as time-continuous dynamical systems that model the evolution in time of neural population activation. Population level neural processes bring about the attentional selection of objects, the estimation of object shape and pose, and the mapping of pose parameters to suitable movement parameters. Once a target object has been selected, its pose parameters couple into the neural dynamics of movement generation so that changes of pose are propagated through the architecture to update the performed movement online. Implementing the neural architecture on an anthropomorphic robot arm equipped with a Kinect sensor, we evaluate the model by grasping wooden objects. Their size, shape, and pose are estimated from a neural model of scene perception that is based on feature fields. The sequential organization of a reach and grasp act emerges from a sequence of dynamic instabilities within a neural dynamics of behavioral organization, that effectively switches the neural controllers from one phase of the action to the next. Trajectory formation itself is driven by a dynamical systems version of

  7. A Neural Dynamic Architecture for Reaching and Grasping Integrates Perception and Movement Generation and Enables On-Line Updating.

    Science.gov (United States)

    Knips, Guido; Zibner, Stephan K U; Reimann, Hendrik; Schöner, Gregor

    2017-01-01

    Reaching for objects and grasping them is a fundamental skill for any autonomous robot that interacts with its environment. Although this skill seems trivial to adults, who effortlessly pick up even objects they have never seen before, it is hard for other animals, for human infants, and for most autonomous robots. Any time during movement preparation and execution, human reaching movement are updated if the visual scene changes (with a delay of about 100 ms). The capability for online updating highlights how tightly perception, movement planning, and movement generation are integrated in humans. Here, we report on an effort to reproduce this tight integration in a neural dynamic process model of reaching and grasping that covers the complete path from visual perception to movement generation within a unified modeling framework, Dynamic Field Theory. All requisite processes are realized as time-continuous dynamical systems that model the evolution in time of neural population activation. Population level neural processes bring about the attentional selection of objects, the estimation of object shape and pose, and the mapping of pose parameters to suitable movement parameters. Once a target object has been selected, its pose parameters couple into the neural dynamics of movement generation so that changes of pose are propagated through the architecture to update the performed movement online. Implementing the neural architecture on an anthropomorphic robot arm equipped with a Kinect sensor, we evaluate the model by grasping wooden objects. Their size, shape, and pose are estimated from a neural model of scene perception that is based on feature fields. The sequential organization of a reach and grasp act emerges from a sequence of dynamic instabilities within a neural dynamics of behavioral organization, that effectively switches the neural controllers from one phase of the action to the next. Trajectory formation itself is driven by a dynamical systems version of

  8. Integrated genomic and BMI analysis for type 2 diabetes risk assessment

    Science.gov (United States)

    Lebrón-Aldea, Dayanara; Dhurandhar, Emily J.; Pérez-Rodríguez, Paulino; Klimentidis, Yann C.; Tiwari, Hemant K.; Vazquez, Ana I.

    2015-01-01

    Type 2 Diabetes (T2D) is a chronic disease arising from the development of insulin absence or resistance within the body, and a complex interplay of environmental and genetic factors. The incidence of T2D has increased throughout the last few decades, together with the occurrence of the obesity epidemic. The consideration of variants identified by Genome Wide Association Studies (GWAS) into risk assessment models for T2D could aid in the identification of at-risk patients who could benefit from preventive medicine. In this study, we build several risk assessment models, evaluated with two different classification approaches (Logistic Regression and Neural Networks), to measure the effect of including genetic information in the prediction of T2D. We used data from to the Original and the Offspring cohorts of the Framingham Heart Study, which provides phenotypic and genetic information for 5245 subjects (4306 controls and 939 cases). Models were built by using several covariates: gender, exposure time, cohort, body mass index (BMI), and 65 SNPs associated to T2D. We fitted Logistic Regressions and Bayesian Regularized Neural Networks and then assessed their predictive ability by using a ten-fold cross validation. We found that the inclusion of genetic information into the risk assessment models increased the predictive ability by 2%, when compared to the baseline model. Furthermore, the models that included BMI at the onset of diabetes as a possible effector, gave an improvement of 6% in the area under the curve derived from the ROC analysis. The highest AUC achieved (0.75) belonged to the model that included BMI, and a genetic score based on the 65 established T2D-associated SNPs. Finally, the inclusion of SNPs and BMI raised predictive ability in all models as expected; however, results from the AUC in Neural Networks and Logistic Regression did not differ significantly in their prediction accuracy. PMID:25852736

  9. Integrated genomic and BMI analysis for type 2 diabetes risk assessment.

    Directory of Open Access Journals (Sweden)

    Dayanara eLebrón-Aldea

    2015-03-01

    Full Text Available Type 2 Diabetes (T2D is a chronic disease arising from the development of insulin absence or resistance within the body, and a complex interplay of environmental and genetic factors. The incidence of T2D has increased throughout the last few decades, together with the occurrence of the obesity epidemic. The consideration of variants identified by Genome Wide Association Studies (GWAS into risk assessment models for T2D could aid in the identification of at-risk patients who could benefit from preventive medicine. In this study, we build several risk assessment models, and evaluated them with two different classification approaches (Logistic Regression and Neural Networks, to measure the effect of including genetic information in the prediction of T2D. We used data from to the Original and the Offspring cohorts of the Framingham Heart Study, which provides phenotypic and genetic information for 5,245 subjects (4,306 controls and 939 cases. Models were built by using several covariates: gender, exposure time, cohort, body mass index (BMI, and 65 established T2D-associated SNPs. We fitted Logistic Regressions and Bayesian Regularized Neural Network and then assessed their predictive ability by using a ten-fold cross validation. We found that the inclusion of genetic information into the risk assessment models increased the predictive ability by 2%, when compared to the baseline model. Furthermore, the models that included BMI at the onset of diabetes as a possible effector, gave an improvement of 6% in the area under the curve derived from the ROC analysis. The highest AUC achieved (0.75 belonged to the model that included BMI, and a genetic score based on the 65 established T2D-associated SNPs. Finally, the inclusion of SNPs and BMI raised predictive ability in all models as expected; however, results from the AUC in Neural Networks and Logistic Regression did not differ significantly in their prediction accuracy.

  10. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Directory of Open Access Journals (Sweden)

    Hongbao Cao

    Full Text Available Various types of genomic data (e.g., SNPs and mRNA transcripts have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls and expression data for 22283 genes in 80 subjects (40 cases and 40 controls to identify significant genes for osteoporosis (OP. Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'. Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc. that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  11. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Science.gov (United States)

    Cao, Hongbao; Lei, Shufeng; Deng, Hong-Wen; Wang, Yu-Ping

    2012-01-01

    Various types of genomic data (e.g., SNPs and mRNA transcripts) have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions) that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC) method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls) and expression data for 22283 genes in 80 subjects (40 cases and 40 controls) to identify significant genes for osteoporosis (OP). Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'). Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc.) that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  12. Construction of an ortholog database using the semantic web technology for integrative analysis of genomic data.

    Science.gov (United States)

    Chiba, Hirokazu; Nishide, Hiroyo; Uchiyama, Ikuo

    2015-01-01

    Recently, various types of biological data, including genomic sequences, have been rapidly accumulating. To discover biological knowledge from such growing heterogeneous data, a flexible framework for data integration is necessary. Ortholog information is a central resource for interlinking corresponding genes among different organisms, and the Semantic Web provides a key technology for the flexible integration of heterogeneous data. We have constructed an ortholog database using the Semantic Web technology, aiming at the integration of numerous genomic data and various types of biological information. To formalize the structure of the ortholog information in the Semantic Web, we have constructed the Ortholog Ontology (OrthO). While the OrthO is a compact ontology for general use, it is designed to be extended to the description of database-specific concepts. On the basis of OrthO, we described the ortholog information from our Microbial Genome Database for Comparative Analysis (MBGD) in the form of Resource Description Framework (RDF) and made it available through the SPARQL endpoint, which accepts arbitrary queries specified by users. In this framework based on the OrthO, the biological data of different organisms can be integrated using the ortholog information as a hub. Besides, the ortholog information from different data sources can be compared with each other using the OrthO as a shared ontology. Here we show some examples demonstrating that the ortholog information described in RDF can be used to link various biological data such as taxonomy information and Gene Ontology. Thus, the ortholog database using the Semantic Web technology can contribute to biological knowledge discovery through integrative data analysis.

  13. Integrated physical, genetic and genome map of chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Varshney, Rajeev K; Mir, Reyazul Rouf; Bhatia, Sabhyata; Thudi, Mahendar; Hu, Yuqin; Azam, Sarwar; Zhang, Yong; Jaganathan, Deepa; You, Frank M; Gao, Jinliang; Riera-Lizarazu, Oscar; Luo, Ming-Cheng

    2014-03-01

    Physical map of chickpea was developed for the reference chickpea genotype (ICC 4958) using bacterial artificial chromosome (BAC) libraries targeting 71,094 clones (~12× coverage). High information content fingerprinting (HICF) of these clones gave high-quality fingerprinting data for 67,483 clones, and 1,174 contigs comprising 46,112 clones and 3,256 singletons were defined. In brief, 574 Mb genome size was assembled in 1,174 contigs with an average of 0.49 Mb per contig and 3,256 singletons represent 407 Mb genome. The physical map was linked with two genetic maps with the help of 245 BAC-end sequence (BES)-derived simple sequence repeat (SSR) markers. This allowed locating some of the BACs in the vicinity of some important quantitative trait loci (QTLs) for drought tolerance and reistance to Fusarium wilt and Ascochyta blight. In addition, fingerprinted contig (FPC) assembly was also integrated with the draft genome sequence of chickpea. As a result, ~965 BACs including 163 minimum tilling path (MTP) clones could be mapped on eight pseudo-molecules of chickpea forming 491 hypothetical contigs representing 54,013,992 bp (~54 Mb) of the draft genome. Comprehensive analysis of markers in abiotic and biotic stress tolerance QTL regions led to identification of 654, 306 and 23 genes in drought tolerance "QTL-hotspot" region, Ascochyta blight resistance QTL region and Fusarium wilt resistance QTL region, respectively. Integrated physical, genetic and genome map should provide a foundation for cloning and isolation of QTLs/genes for molecular dissection of traits as well as markers for molecular breeding for chickpea improvement.

  14. Recurrent Neural Network Approach Based on the Integral Representation of the Drazin Inverse.

    Science.gov (United States)

    Stanimirović, Predrag S; Živković, Ivan S; Wei, Yimin

    2015-10-01

    In this letter, we present the dynamical equation and corresponding artificial recurrent neural network for computing the Drazin inverse for arbitrary square real matrix, without any restriction on its eigenvalues. Conditions that ensure the stability of the defined recurrent neural network as well as its convergence toward the Drazin inverse are considered. Several illustrative examples present the results of computer simulations.

  15. Modeling development of natural multi-sensory integration using neural self-organisation and probabilistic population codes

    Science.gov (United States)

    Bauer, Johannes; Dávila-Chacón, Jorge; Wermter, Stefan

    2015-10-01

    Humans and other animals have been shown to perform near-optimally in multi-sensory integration tasks. Probabilistic population codes (PPCs) have been proposed as a mechanism by which optimal integration can be accomplished. Previous approaches have focussed on how neural networks might produce PPCs from sensory input or perform calculations using them, like combining multiple PPCs. Less attention has been given to the question of how the necessary organisation of neurons can arise and how the required knowledge about the input statistics can be learned. In this paper, we propose a model of learning multi-sensory integration based on an unsupervised learning algorithm in which an artificial neural network learns the noise characteristics of each of its sources of input. Our algorithm borrows from the self-organising map the ability to learn latent-variable models of the input and extends it to learning to produce a PPC approximating a probability density function over the latent variable behind its (noisy) input. The neurons in our network are only required to perform simple calculations and we make few assumptions about input noise properties and tuning functions. We report on a neurorobotic experiment in which we apply our algorithm to multi-sensory integration in a humanoid robot to demonstrate its effectiveness and compare it to human multi-sensory integration on the behavioural level. We also show in simulations that our algorithm performs near-optimally under certain plausible conditions, and that it reproduces important aspects of natural multi-sensory integration on the neural level.

  16. A Profile of Native Integration Sites Used by φC31 Integrase in the Bovine Genome

    Institute of Scientific and Technical Information of China (English)

    Lijuan Qu; Qingwen Ma; Zaiwei Zhou; Haiyan Ma; Ying Huang; Shuzhen Huang; Fanyi Zeng; Yitao Zeng

    2012-01-01

    The Streptomyces phage φC31 integrase can efficiently target attB-beadng transgenes to endogenous pseudo attP sites within mammalian genomes.To better understand the activity of φC31 integrase in the bovine genome,DNA sequences of 44 integration events were analyzed,and 32 pseudo attP sites were identified.The majority of these sites share a sequence motif that contains inverted repeats and has similarities to wild-type attP site.Genomic DNA flanking these sites typically contained repetitive sequence elements,such as short and long interspersed repetitive elements.These sequence features indicate that DNA sequence recognition plays an important role in guiding φC31-mediated site-specific integration.In addition,BF27 integration hotspot sites were identified in the bovine genome,which accounted for 13.6% of all isolated integration events and mapped to an intron of the deleted in liver cancer 1 (DLC1) gene.Also we found that the pseudo attP sites in the bovine genome had other features in common with those in the human genome.This study represents the first time that the sequence features of pseudo attP sites in the bovine genome were analyzed.We conclude that this sitespecific integrase system has great potential for applied modifications of the bovine genome.

  17. Integrated Database And Knowledge Base For Genomic Prospective Cohort Study In Tohoku Medical Megabank Toward Personalized Prevention And Medicine.

    Science.gov (United States)

    Ogishima, Soichi; Takai, Takako; Shimokawa, Kazuro; Nagaie, Satoshi; Tanaka, Hiroshi; Nakaya, Jun

    2015-01-01

    The Tohoku Medical Megabank project is a national project to revitalization of the disaster area in the Tohoku region by the Great East Japan Earthquake, and have conducted large-scale prospective genome-cohort study. Along with prospective genome-cohort study, we have developed integrated database and knowledge base which will be key database for realizing personalized prevention and medicine.

  18. Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework.

    Science.gov (United States)

    Yang, Hai; Wei, Qiang; Zhong, Xue; Yang, Hushan; Li, Bingshan

    2017-02-15

    Comprehensive catalogue of genes that drive tumor initiation and progression in cancer is key to advancing diagnostics, therapeutics and treatment. Given the complexity of cancer, the catalogue is far from complete yet. Increasing evidence shows that driver genes exhibit consistent aberration patterns across multiple-omics in tumors. In this study, we aim to leverage complementary information encoded in each of the omics data to identify novel driver genes through an integrative framework. Specifically, we integrated mutations, gene expression, DNA copy numbers, DNA methylation and protein abundance, all available in The Cancer Genome Atlas (TCGA) and developed iDriver, a non-parametric Bayesian framework based on multivariate statistical modeling to identify driver genes in an unsupervised fashion. iDriver captures the inherent clusters of gene aberrations and constructs the background distribution that is used to assess and calibrate the confidence of driver genes identified through multi-dimensional genomic data. We applied the method to 4 cancer types in TCGA and identified candidate driver genes that are highly enriched with known drivers. (e.g.: P < 3.40 × 10 -36 for breast cancer). We are particularly interested in novel genes and observed multiple lines of supporting evidence. Using systematic evaluation from multiple independent aspects, we identified 45 candidate driver genes that were not previously known across these 4 cancer types. The finding has important implications that integrating additional genomic data with multivariate statistics can help identify cancer drivers and guide the next stage of cancer genomics research. The C ++ source code is freely available at https://medschool.vanderbilt.edu/cgg/ . hai.yang@vanderbilt.edu or bingshan.li@Vanderbilt.Edu. Supplementary data are available at Bioinformatics online.

  19. TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.

    Science.gov (United States)

    Cumbo, Fabio; Fiscon, Giulia; Ceri, Stefano; Masseroli, Marco; Weitschek, Emanuel

    2017-01-03

    Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments.

  20. VarB Plus: An Integrated Tool for Visualization of Genome Variation Datasets

    KAUST Repository

    Hidayah, Lailatul

    2012-07-01

    Research on genomic sequences has been improving significantly as more advanced technology for sequencing has been developed. This opens enormous opportunities for sequence analysis. Various analytical tools have been built for purposes such as sequence assembly, read alignments, genome browsing, comparative genomics, and visualization. From the visualization perspective, there is an increasing trend towards use of large-scale computation. However, more than power is required to produce an informative image. This is a challenge that we address by providing several ways of representing biological data in order to advance the inference endeavors of biologists. This thesis focuses on visualization of variations found in genomic sequences. We develop several visualization functions and embed them in an existing variation visualization tool as extensions. The tool we improved is named VarB, hence the nomenclature for our enhancement is VarB Plus. To the best of our knowledge, besides VarB, there is no tool that provides the capability of dynamic visualization of genome variation datasets as well as statistical analysis. Dynamic visualization allows users to toggle different parameters on and off and see the results on the fly. The statistical analysis includes Fixation Index, Relative Variant Density, and Tajima’s D. Hence we focused our efforts on this tool. The scope of our work includes plots of per-base genome coverage, Principal Coordinate Analysis (PCoA), integration with a read alignment viewer named LookSeq, and visualization of geo-biological data. In addition to description of embedded functionalities, significance, and limitations, future improvements are discussed. The result is four extensions embedded successfully in the original tool, which is built on the Qt framework in C++. Hence it is portable to numerous platforms. Our extensions have shown acceptable execution time in a beta testing with various high-volume published datasets, as well as positive

  1. Modeling and interoperability of heterogeneous genomic big data for integrative processing and querying.

    Science.gov (United States)

    Masseroli, Marco; Kaitoua, Abdulrahman; Pinoli, Pietro; Ceri, Stefano

    2016-12-01

    While a huge amount of (epi)genomic data of multiple types is becoming available by using Next Generation Sequencing (NGS) technologies, the most important emerging problem is the so-called tertiary analysis, concerned with sense making, e.g., discovering how different (epi)genomic regions and their products interact and cooperate with each other. We propose a paradigm shift in tertiary analysis, based on the use of the Genomic Data Model (GDM), a simple data model which links genomic feature data to their associated experimental, biological and clinical metadata. GDM encompasses all the data formats which have been produced for feature extraction from (epi)genomic datasets. We specifically describe the mapping to GDM of SAM (Sequence Alignment/Map), VCF (Variant Call Format), NARROWPEAK (for called peaks produced by NGS ChIP-seq or DNase-seq methods), and BED (Browser Extensible Data) formats, but GDM supports as well all the formats describing experimental datasets (e.g., including copy number variations, DNA somatic mutations, or gene expressions) and annotations (e.g., regarding transcription start sites, genes, enhancers or CpG islands). We downloaded and integrated samples of all the above-mentioned data types and formats from multiple sources. The GDM is able to homogeneously describe semantically heterogeneous data and makes the ground for providing data interoperability, e.g., achieved through the GenoMetric Query Language (GMQL), a high-level, declarative query language for genomic big data. The combined use of the data model and the query language allows comprehensive processing of multiple heterogeneous data, and supports the development of domain-specific data-driven computations and bio-molecular knowledge discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Neural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.

    LENUS (Irish Health Repository)

    Rose, Emma J

    2013-09-01

    The single nucleotide polymorphism rs10503253 within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2 has been identified as genome-wide significant for schizophrenia (SZ). This gene is of unknown function but has been implicated in multiple neurodevelopmental disorders that impact upon cognition, leading us to hypothesize that an effect on brain structure and function underlying cognitive processes may be part of the mechanism by which CMSD1 increases illness risk. To test this hypothesis, we investigated this CSMD1 variant in vivo in healthy participants in a magnetic resonance imaging (MRI) study comprised of both fMRI of spatial working memory (N = 50) and a voxel-based morphometry investigation of grey and white matter (WM) volume (N = 150). Analyses of these data indicated that the risk "A" allele was associated with comparatively reduced cortical activations in BA18, that is, middle occipital gyrus and cuneus; posterior brain regions that support maintenance processes during performance of a spatial working memory task. Conversely, there was an absence of significant structural differences in brain volume (i.e., grey or WM). In accordance with previous evidence, these data suggest that CSMD1 may mediate brain function related to cognitive processes (i.e., executive function); with the relatively deleterious effects of the identified "A" risk allele on brain activity possibly constituting part of the mechanism by which CSMD1 increases schizophrenia risk.

  3. Messenger RNA- versus retrovirus-based induced pluripotent stem cell reprogramming strategies: analysis of genomic integrity.

    Science.gov (United States)

    Steichen, Clara; Luce, Eléanor; Maluenda, Jérôme; Tosca, Lucie; Moreno-Gimeno, Inmaculada; Desterke, Christophe; Dianat, Noushin; Goulinet-Mainot, Sylvie; Awan-Toor, Sarah; Burks, Deborah; Marie, Joëlle; Weber, Anne; Tachdjian, Gérard; Melki, Judith; Dubart-Kupperschmitt, Anne

    2014-06-01

    The use of synthetic messenger RNAs to generate human induced pluripotent stem cells (iPSCs) is particularly appealing for potential regenerative medicine applications, because it overcomes the common drawbacks of DNA-based or virus-based reprogramming strategies, including transgene integration in particular. We compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus-derived iPSCs generated in strictly comparable conditions, by single-nucleotide polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA-derived iPSCs do not differ significantly from the parental fibroblasts in SNP analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs seemed independent of the reprogramming method, instead appearing to be clone-dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs differentiated efficiently into hepatoblasts and that these cells did not load additional CNVs during differentiation. The integration-free hepatoblasts that were generated constitute a new tool for the study of diseased hepatocytes derived from patients' iPSCs and their use in the context of stem cell-derived hepatocyte transplantation. Our findings also highlight the need to conduct careful studies on genome integrity for the selection of iPSC lines before using them for further applications.

  4. Precision Interval Estimation of the Response Surface by Means of an Integrated Algorithm of Neural Network and Linear Regression

    Science.gov (United States)

    Lo, Ching F.

    1999-01-01

    The integration of Radial Basis Function Networks and Back Propagation Neural Networks with the Multiple Linear Regression has been accomplished to map nonlinear response surfaces over a wide range of independent variables in the process of the Modem Design of Experiments. The integrated method is capable to estimate the precision intervals including confidence and predicted intervals. The power of the innovative method has been demonstrated by applying to a set of wind tunnel test data in construction of response surface and estimation of precision interval.

  5. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

    Directory of Open Access Journals (Sweden)

    Juliana Gonçalves

    2016-01-01

    Full Text Available Chromosomal fragile sites (FSs are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs. The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data.

  6. MIPS Arabidopsis thaliana Database (MAtDB): an integrated biological knowledge resource for plant genomics.

    Science.gov (United States)

    Schoof, Heiko; Ernst, Rebecca; Nazarov, Vladimir; Pfeifer, Lukas; Mewes, Hans-Werner; Mayer, Klaus F X

    2004-01-01

    Arabidopsis thaliana is the most widely studied model plant. Functional genomics is intensively underway in many laboratories worldwide. Beyond the basic annotation of the primary sequence data, the annotated genetic elements of Arabidopsis must be linked to diverse biological data and higher order information such as metabolic or regulatory pathways. The MIPS Arabidopsis thaliana database MAtDB aims to provide a comprehensive resource for Arabidopsis as a genome model that serves as a primary reference for research in plants and is suitable for transfer of knowledge to other plants, especially crops. The genome sequence as a common backbone serves as a scaffold for the integration of data, while, in a complementary effort, these data are enhanced through the application of state-of-the-art bioinformatics tools. This information is visualized on a genome-wide and a gene-by-gene basis with access both for web users and applications. This report updates the information given in a previous report and provides an outlook on further developments. The MAtDB web interface can be accessed at http://mips.gsf.de/proj/thal/db.

  7. MicrobesOnline: an integrated portal for comparative and functional genomics

    Energy Technology Data Exchange (ETDEWEB)

    Dehal, Paramvir; Joachimiak, Marcin; Price, Morgan; Bates, John; Baumohl, Jason; Chivian, Dylan; Friedland, Greg; Huang, Kathleen; Keller, Keith; Novichkov, Pavel; Dubchak, Inna; Alm, Eric; Arkin, Adam

    2011-07-14

    Since 2003, MicrobesOnline (http://www.microbesonline.org) has been providing a community resource for comparative and functional genome analysis. The portal includes over 1000 complete genomes of bacteria, archaea and fungi and thousands of expression microarrays from diverse organisms ranging from model organisms such as Escherichia coli and Saccharomyces cerevisiae to environmental microbes such as Desulfovibrio vulgaris and Shewanella oneidensis. To assist in annotating genes and in reconstructing their evolutionary history, MicrobesOnline includes a comparative genome browser based on phylogenetic trees for every gene family as well as a species tree. To identify co-regulated genes, MicrobesOnline can search for genes based on their expression profile, and provides tools for identifying regulatory motifs and seeing if they are conserved. MicrobesOnline also includes fast phylogenetic profile searches, comparative views of metabolic pathways, operon predictions, a workbench for sequence analysis and integration with RegTransBase and other microbial genome resources. The next update of MicrobesOnline will contain significant new functionality, including comparative analysis of metagenomic sequence data. Programmatic access to the database, along with source code and documentation, is available at http://microbesonline.org/programmers.html.

  8. ZikaVR: An Integrated Zika Virus Resource for Genomics, Proteomics, Phylogenetic and Therapeutic Analysis

    Science.gov (United States)

    Gupta, Amit Kumar; Kaur, Karambir; Rajput, Akanksha; Dhanda, Sandeep Kumar; Sehgal, Manika; Khan, Md. Shoaib; Monga, Isha; Dar, Showkat Ahmad; Singh, Sandeep; Nagpal, Gandharva; Usmani, Salman Sadullah; Thakur, Anamika; Kaur, Gazaldeep; Sharma, Shivangi; Bhardwaj, Aman; Qureshi, Abid; Raghava, Gajendra Pal Singh; Kumar, Manoj

    2016-01-01

    Current Zika virus (ZIKV) outbreaks that spread in several areas of Africa, Southeast Asia, and in pacific islands is declared as a global health emergency by World Health Organization (WHO). It causes Zika fever and illness ranging from severe autoimmune to neurological complications in humans. To facilitate research on this virus, we have developed an integrative multi-omics platform; ZikaVR (http://bioinfo.imtech.res.in/manojk/zikavr/), dedicated to the ZIKV genomic, proteomic and therapeutic knowledge. It comprises of whole genome sequences, their respective functional information regarding proteins, genes, and structural content. Additionally, it also delivers sophisticated analysis such as whole-genome alignments, conservation and variation, CpG islands, codon context, usage bias and phylogenetic inferences at whole genome and proteome level with user-friendly visual environment. Further, glycosylation sites and molecular diagnostic primers were also analyzed. Most importantly, we also proposed potential therapeutically imperative constituents namely vaccine epitopes, siRNAs, miRNAs, sgRNAs and repurposing drug candidates. PMID:27633273

  9. GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome.

    Science.gov (United States)

    Simovski, Boris; Vodák, Daniel; Gundersen, Sveinung; Domanska, Diana; Azab, Abdulrahman; Holden, Lars; Holden, Marit; Grytten, Ivar; Rand, Knut; Drabløs, Finn; Johansen, Morten; Mora, Antonio; Lund-Andersen, Christin; Fromm, Bastian; Eskeland, Ragnhild; Gabrielsen, Odd Stokke; Ferkingstad, Egil; Nakken, Sigve; Bengtsen, Mads; Nederbragt, Alexander Johan; Thorarensen, Hildur Sif; Akse, Johannes Andreas; Glad, Ingrid; Hovig, Eivind; Sandve, Geir Kjetil

    2017-07-01

    Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.

  10. LegumeIP: an integrative database for comparative genomics and transcriptomics of model legumes.

    Science.gov (United States)

    Li, Jun; Dai, Xinbin; Liu, Tingsong; Zhao, Patrick Xuechun

    2012-01-01

    Legumes play a vital role in maintaining the nitrogen cycle of the biosphere. They conduct symbiotic nitrogen fixation through endosymbiotic relationships with bacteria in root nodules. However, this and other characteristics of legumes, including mycorrhization, compound leaf development and profuse secondary metabolism, are absent in the typical model plant Arabidopsis thaliana. We present LegumeIP (http://plantgrn.noble.org/LegumeIP/), an integrative database for comparative genomics and transcriptomics of model legumes, for studying gene function and genome evolution in legumes. LegumeIP compiles gene and gene family information, syntenic and phylogenetic context and tissue-specific transcriptomic profiles. The database holds the genomic sequences of three model legumes, Medicago truncatula, Glycine max and Lotus japonicus plus two reference plant species, A. thaliana and Populus trichocarpa, with annotations based on UniProt, InterProScan, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases. LegumeIP also contains large-scale microarray and RNA-Seq-based gene expression data. Our new database is capable of systematic synteny analysis across M. truncatula, G. max, L. japonicas and A. thaliana, as well as construction and phylogenetic analysis of gene families across the five hosted species. Finally, LegumeIP provides comprehensive search and visualization tools that enable flexible queries based on gene annotation, gene family, synteny and relative gene expression.

  11. MicrobesOnline: an integrated portal for comparative and functional genomics

    Energy Technology Data Exchange (ETDEWEB)

    Dehal, Paramvir S.; Joachimiak, Marcin P.; Price, Morgan N.; Bates, John T.; Baumohl, Jason K.; Chivian, Dylan; Friedland, Greg D.; Huang, Katherine H.; Keller, Keith; Novichkov, Pavel S.; Dubchak, Inna L.; Alm, Eric J.; Arkin, Adam P.

    2009-09-17

    Since 2003, MicrobesOnline (http://www.microbesonline.org) has been providing a community resource for comparative and functional genome analysis. The portal includes over 1000 complete genomes of bacteria, archaea and fungi and thousands of expression microarrays from diverse organisms ranging from model organisms such as Escherichia coli and Saccharomyces cerevisiae to environmental microbes such as Desulfovibrio vulgaris and Shewanella oneidensis. To assist in annotating genes and in reconstructing their evolutionary history, MicrobesOnline includes a comparative genome browser based on phylogenetic trees for every gene family as well as a species tree. To identify co-regulated genes, MicrobesOnline can search for genes based on their expression profile, and provides tools for identifying regulatory motifs and seeing if they are conserved. MicrobesOnline also includes fast phylogenetic profile searches, comparative views of metabolic pathways, operon predictions, a workbench for sequence analysis and integration with RegTransBase and other microbial genome resources. The next update of MicrobesOnline will contain significant new functionality, including comparative analysis of metagenomic sequence data. Programmatic access to the database, along with source code and documentation, is available at http://microbesonline.org/programmers.html.

  12. Genomic Integrity Detection of In Vitro Irradiated Banana Using Microsatellite Marker.

    Directory of Open Access Journals (Sweden)

    Nina Ratna Djuita

    2010-11-01

    Full Text Available Genomic Integrity Detection of In Vitro Irradiated Banana Using Microsatellite Marker. The research aims todetect genomic integrity of in vitro irradiated banana using microsatellite marker. These studies were done on bananacv. Pisang Mas irradiated by 15 Gy of gamma ray. The DNA was isolated from each accesion following Dixie.Amplification of DNA products were done by Perkin Elmer Gene Amp PCR 2400 using ten primers, and thenelectroforesis in agarose 1%. Finally a vertical polyacrylamide gel electroforesis was run and the products werevisualized by silver staining. The result shown that among the primers tested, eight primers produced clear, discrete,and reproducible bands. Number of DNA band exhibited ranging from one to two, following the ploidy level of pisangMas which is a diploid banana cultivar (AA. One band suggest homozygote allele while two bands showedheterozygote allele. Out of eight primers, six primers produced different allele among irradiated, in vitro, and in vivocontrol plant. Meanwhile, for the other two primers the allele were monomorph for all the accessions examined.Genomic modification was observed at all irradiated plants. The modification can happened at zygosity of certain allelethat may change from heterozygote to homozygote or vice versa. While modification in allele size that underlyinggenomic instability could be caused by several genetic events such as deletion, insertion, and amplification ofnucleotides.

  13. Integrating experimental and analytic approaches to improve data quality in genome-wide RNAi screens.

    Science.gov (United States)

    Zhang, Xiaohua Douglas; Espeseth, Amy S; Johnson, Eric N; Chin, Jayne; Gates, Adam; Mitnaul, Lyndon J; Marine, Shane D; Tian, Jenny; Stec, Eric M; Kunapuli, Priya; Holder, Dan J; Heyse, Joseph F; Strulovici, Berta; Ferrer, Marc

    2008-06-01

    RNA interference (RNAi) not only plays an important role in drug discovery but can also be developed directly into drugs. RNAi high-throughput screening (HTS) biotechnology allows us to conduct genome-wide RNAi research. A central challenge in genome-wide RNAi research is to integrate both experimental and computational approaches to obtain high quality RNAi HTS assays. Based on our daily practice in RNAi HTS experiments, we propose the implementation of 3 experimental and analytic processes to improve the quality of data from RNAi HTS biotechnology: (1) select effective biological controls; (2) adopt appropriate plate designs to display and/or adjust for systematic errors of measurement; and (3) use effective analytic metrics to assess data quality. The applications in 5 real RNAi HTS experiments demonstrate the effectiveness of integrating these processes to improve data quality. Due to the effectiveness in improving data quality in RNAi HTS experiments, the methods and guidelines contained in the 3 experimental and analytic processes are likely to have broad utility in genome-wide RNAi research.

  14. Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis.

    Science.gov (United States)

    Low, Teck Yew; van Heesch, Sebastiaan; van den Toorn, Henk; Giansanti, Piero; Cristobal, Alba; Toonen, Pim; Schafer, Sebastian; Hübner, Norbert; van Breukelen, Bas; Mohammed, Shabaz; Cuppen, Edwin; Heck, Albert J R; Guryev, Victor

    2013-12-12

    Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Identifying master regulators of cancer and their downstream targets by integrating genomic and epigenomic features.

    Science.gov (United States)

    Gevaert, Olivier; Plevritis, Sylvia

    2013-01-01

    Vast amounts of molecular data characterizing the genome, epigenome and transcriptome are becoming available for a variety of cancers. The current challenge is to integrate these diverse layers of molecular biology information to create a more comprehensive view of key biological processes underlying cancer. We developed a biocomputational algorithm that integrates copy number, DNA methylation, and gene expression data to study master regulators of cancer and identify their targets. Our algorithm starts by generating a list of candidate driver genes based on the rationale that genes that are driven by multiple genomic events in a subset of samples are unlikely to be randomly deregulated. We then select the master regulators from the candidate driver and identify their targets by inferring the underlying regulatory network of gene expression. We applied our biocomputational algorithm to identify master regulators and their targets in glioblastoma multiforme (GBM) and serous ovarian cancer. Our results suggest that the expression of candidate drivers is more likely to be influenced by copy number variations than DNA methylation. Next, we selected the master regulators and identified their downstream targets using module networks analysis. As a proof-of-concept, we show that the GBM and ovarian cancer module networks recapitulate known processes in these cancers. In addition, we identify master regulators that have not been previously reported and suggest their likely role. In summary, focusing on genes whose expression can be explained by their genomic and epigenomic aberrations is a promising strategy to identify master regulators of cancer.

  16. Quantitative and Qualitative Proteome Characteristics Extracted from In-Depth Integrated Genomics and Proteomics Analysis

    Directory of Open Access Journals (Sweden)

    Teck Yew Low

    2013-12-01

    Full Text Available Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner.

  17. Advances in the integration of transcriptional regulatory information into genome-scale metabolic models.

    Science.gov (United States)

    Vivek-Ananth, R P; Samal, Areejit

    2016-09-01

    A major goal of systems biology is to build predictive computational models of cellular metabolism. Availability of complete genome sequences and wealth of legacy biochemical information has led to the reconstruction of genome-scale metabolic networks in the last 15 years for several organisms across the three domains of life. Due to paucity of information on kinetic parameters associated with metabolic reactions, the constraint-based modelling approach, flux balance analysis (FBA), has proved to be a vital alternative to investigate the capabilities of reconstructed metabolic networks. In parallel, advent of high-throughput technologies has led to the generation of massive amounts of omics data on transcriptional regulation comprising mRNA transcript levels and genome-wide binding profile of transcriptional regulators. A frontier area in metabolic systems biology has been the development of methods to integrate the available transcriptional regulatory information into constraint-based models of reconstructed metabolic networks in order to increase the predictive capabilities of computational models and understand the regulation of cellular metabolism. Here, we review the existing methods to integrate transcriptional regulatory information into constraint-based models of metabolic networks.

  18. The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells

    Directory of Open Access Journals (Sweden)

    Swapna Kollu

    2015-06-01

    Full Text Available To ensure accurate genomic segregation, cells evolved the spindle assembly checkpoint (SAC, whose role in adult stem cells remains unknown. Inducible perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in skeletal muscle stem cells shows the SAC to be critical for normal muscle growth, repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting differentiation even under inductive conditions. p21CIP1 is responsible for these SAC-deficient phenotypes. Despite aneuploidy’s correlation with aging, we find that aged proliferating muscle stem cells display robust SAC activity without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to safeguard their genomic integrity. The SAC prevents chromosome missegregation and, if it fails, p21CIP1-dependent G1 arrest limits cellular propagation and tissue integration. These mechanisms ensure that muscle stem cells with compromised genomes do not contribute to tissue homeostasis.

  19. The importance of safeguarding genome integrity in germination and seed longevity.

    Science.gov (United States)

    Waterworth, Wanda M; Bray, Clifford M; West, Christopher E

    2015-06-01

    Seeds are important to agriculture and conservation of plant biodiversity. In agriculture, seed germination performance is an important determinant of crop yield, in particular under adverse climatic conditions. Deterioration in seed quality is associated with the accumulation of cellular damage to macromolecules including lipids, protein, and DNA. Mechanisms that mitigate the deleterious cellular damage incurred in the quiescent state and in cycles of desiccation-hydration are crucial for the maintenance of seed viability and germination vigour. In early-imbibing seeds, damage to the embryo genome must be repaired prior to initiation of cell division to minimize growth inhibition and mutation of genetic information. Here we review recent advances that have established molecular links between genome integrity and seed quality. These studies identified that maintenance of genome integrity is particularly important to the seed stage of the plant lifecycle, revealing new insight into the physiological roles of plant DNA repair and recombination mechanisms. The high conservation of DNA repair and recombination factors across plant species underlines their potential as promising targets for the improvement of crop performance and development of molecular markers for prediction of seed vigour.

  20. Genome-Wide Analysis of Alpharetroviral Integration in Human Hematopoietic Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Arianna Moiani

    2014-05-01

    Full Text Available Gene transfer vectors derived from gamma-retroviruses or lentiviruses are currently used for the gene therapy of genetic or acquired diseases. Retroviral vectors display a non-random integration pattern in the human genome, targeting either regulatory regions (gamma-retroviruses or the transcribed portion of expressed genes (lentiviruses, and have the potential to deregulate gene expression at the transcriptional or post-transcriptional level. A recently developed alternative vector system derives from the avian sarcoma-leukosis alpha-retrovirus (ASLV and shows favorable safety features compared to both gamma-retroviral and lentiviral vectors in preclinical models. We performed a high-throughput analysis of the integration pattern of self-inactivating (SIN alpha-retroviral vectors in human CD34+ hematopoietic stem/progenitor cells (HSPCs and compared it to previously reported gamma-retroviral and lentiviral vectors integration profiles obtained in the same experimental setting. Compared to gamma-retroviral and lentiviral vectors, the SIN-ASLV vector maintains a preference for open chromatin regions, but shows no bias for transcriptional regulatory elements or transcription units, as defined by genomic annotations and epigenetic markers (H3K4me1 and H3K4me3 histone modifications. Importantly, SIN-ASLV integrations do not cluster in hot spots and target potentially dangerous genomic loci, such as the EVI2A/B, RUNX1 and LMO2 proto-oncogenes at a virtually random frequency. These characteristics predict a safer profile for ASLV-derived vectors for clinical applications.

  1. Co-regulation of pluripotency and genetic integrity at the genomic level

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2014-11-01

    Full Text Available The Disposable Soma Theory holds that genetic integrity will be maintained at more pristine levels in germ cells than in somatic cells because of the unique role germ cells play in perpetuating the species. We tested the hypothesis that the same concept applies to pluripotent cells compared to differentiated cells. Analyses of transcriptome and cistrome databases, along with canonical pathway analysis and chromatin immunoprecipitation confirmed differential expression of DNA repair and cell death genes in embryonic stem cells and induced pluripotent stem cells relative to fibroblasts, and predicted extensive direct and indirect interactions between the pluripotency and genetic integrity gene networks in pluripotent cells. These data suggest that enhanced maintenance of genetic integrity is fundamentally linked to the epigenetic state of pluripotency at the genomic level. In addition, these findings demonstrate how a small number of key pluripotency factors can regulate large numbers of downstream genes in a pathway-specific manner.

  2. Advancing Post-Genome Data and System Integration Through Machine Learning

    Directory of Open Access Journals (Sweden)

    Francisco Azuaje

    2006-04-01

    Full Text Available Research on biological data integration has traditionally focused on the development of systems for the maintenance and interconnection of databases. In the next few years, public and private biotechnology organisations will expand their actions to promote the creation of a post-genome semantic web. It has commonly been accepted that artificial intelligence and data mining techniques may support the interpretation of huge amounts of integrated data. But at the same time, these research disciplines are contributing to the creation of content markup languages and sophisticated programs able to exploit the constraints and preferences of user domains. This paper discusses a number of issues on intelligent systems for the integration of bioinformatic resources.

  3. Neural injury alters proliferation and integration of adult-generated neurons in the dentate gyrus

    Science.gov (United States)

    Perederiy, Julia V.; Luikart, Bryan W.; Washburn, Eric K.; Schnell, Eric; Westbrook, Gary L.

    2013-01-01

    Neural plasticity following brain injury illustrates the potential for regeneration in the central nervous system. Lesioning of the perforant path, which innervates the outer 2/3rds of the molecular layer of the dentate gyrus, was one of the first models to demonstrate structural plasticity of mature granule cells (Parnavelas, 1974; Caceres and Steward, 1983; Diekmann et al., 1996). The dentate gyrus also harbors a continuously proliferating population of neuronal precursors that can integrate into functional circuits and show enhanced short-term plasticity (Schmidt-Hieber et al., 2004; Abrous et al., 2005). To examine the response of adult-generated granule cells to unilateral complete transection of the perforant path in vivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP. Lesioning triggered a marked proliferation of newborn neurons. Subsequently, the dendrites of newborn neurons showed reduced complexity within the denervated zone, but dendritic spines still formed in the absence of glutamatergic nerve terminals. Electron micrographs confirmed the lack of intact presynaptic terminals apposing spines on mature cells and on newborn neurons. Newborn neurons, but not mature granule cells, had a higher density of dendritic spines in the inner molecular layer post-lesion, accompanied by an increase in miniature EPSC amplitudes and rise times. Our results indicate that injury causes an increase in newborn neurons and lamina-specific synaptic reorganization, indicative of enhanced plasticity. The presence of de novo dendritic spines in the denervated zone suggests that the post-lesion environment provides the necessary signals for spine formation. PMID:23486947

  4. Self-Organizing Neural Integration of Pose-Motion Features for Human Action Recognition

    Directory of Open Access Journals (Sweden)

    German Ignacio Parisi

    2015-06-01

    Full Text Available The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented towards human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR networks that obtain progressively generalized representations of sensory inputs and learn inherent spatiotemporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best 21 results for a public benchmark of domestic daily actions.

  5. Developing an Intelligent Reservoir Flood Control Decision Support System through Integrating Artificial Neural Networks

    Science.gov (United States)

    Chang, L. C.; Kao, I. F.; Tsai, F. H.; Hsu, H. C.; Yang, S. N.; Shen, H. Y.; Chang, F. J.

    2015-12-01

    Typhoons and storms hit Taiwan several times every year and cause serious flood disasters. Because the mountainous terrain and steep landform rapidly accelerate the speed of flood flow, rivers cannot be a stable source of water supply. Reservoirs become one of the most important and effective floodwater storage facilities. However, real-time operation for reservoir flood control is a continuous and instant decision-making process based on rules, laws, meteorological nowcast, in addition to the immediate rainfall and hydrological data. The achievement of reservoir flood control can effectively mitigate flood disasters and store floodwaters for future uses. In this study, we construct an intelligent decision support system for reservoir flood control through integrating different types of neural networks and the above information to solve this problem. This intelligent reservoir flood control decision support system includes three parts: typhoon track classification, flood forecast and adaptive water release models. This study used the self-organizing map (SOM) for typhoon track clustering, nonlinear autoregressive with exogenous inputs (NARX) for multi-step-ahead reservoir inflow prediction, and adaptive neuro-fuzzy inference system (ANFIS) for reservoir flood control. Before typhoons landfall, we can estimate the entire flood hydrogragh of reservoir inflow by using SOM and make a pre-release strategy and real-time reservoir flood operating by using ANFIS. In the meanwhile, NARX can be constantly used real-time five-hour-ahead inflow prediction for providing the newest flood information. The system has been successfully implemented Typhoons Trami (2013), Fitow (2013) and Matmo (2014) in Shihmen Reservoir.

  6. Self-organizing neural integration of pose-motion features for human action recognition.

    Science.gov (United States)

    Parisi, German I; Weber, Cornelius; Wermter, Stefan

    2015-01-01

    The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented toward human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR) networks that obtain progressively generalized representations of sensory inputs and learn inherent spatio-temporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best results for a public benchmark of domestic daily actions.

  7. In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety.

    Directory of Open Access Journals (Sweden)

    Julie E Cooper

    Full Text Available Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety.Neurospheres generated from yellow fluorescent protein (YFP expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B. Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression.YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16 ± 0.01;43 cells, n = 6 in YFP+ transplanted ENCCs (abolished with TTX. Long-term follow-up (24 months showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites. In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone.Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies.

  8. Neural associative memories for the integration of language, vision and action in an autonomous agent.

    Science.gov (United States)

    Markert, H; Kaufmann, U; Kara Kayikci, Z; Palm, G

    2009-03-01

    Language understanding is a long-standing problem in computer science. However, the human brain is capable of processing complex languages with seemingly no difficulties. This paper shows a model for language understanding using biologically plausible neural networks composed of associative memories. The model is able to deal with ambiguities on the single word and grammatical level. The language system is embedded into a robot in order to demonstrate the correct semantical understanding of the input sentences by letting the robot perform corresponding actions. For that purpose, a simple neural action planning system has been combined with neural networks for visual object recognition and visual attention control mechanisms.

  9. Assessing Vermont's stream health and biological integrity using artificial neural networks and Bayesian methods

    Science.gov (United States)

    Rizzo, D. M.; Fytilis, N.; Stevens, L.

    2012-12-01

    Environmental managers are increasingly required to monitor and forecast long-term effects and vulnerability of biophysical systems to human-generated stresses. Ideally, a study involving both physical and biological assessments conducted concurrently (in space and time) could provide a better understanding of the mechanisms and complex relationships. However, costs and resources associated with monitoring the complex linkages between the physical, geomorphic and habitat conditions and the biological integrity of stream reaches are prohibitive. Researchers have used classification techniques to place individual streams and rivers into a broader spatial context (hydrologic or health condition). Such efforts require environmental managers to gather multiple forms of information - quantitative, qualitative and subjective. We research and develop a novel classification tool that combines self-organizing maps with a Naïve Bayesian classifier to direct resources to stream reaches most in need. The Vermont Agency of Natural Resources has developed and adopted protocols for physical stream geomorphic and habitat assessments throughout the state of Vermont. Separate from these assessments, the Vermont Department of Environmental Conservation monitors the biological communities and the water quality in streams. Our initial hypothesis is that the geomorphic reach assessments and water quality data may be leveraged to reduce error and uncertainty associated with predictions of biological integrity and stream health. We test our hypothesis using over 2500 Vermont stream reaches (~1371 stream miles) assessed by the two agencies. In the development of this work, we combine a Naïve Bayesian classifier with a modified Kohonen Self-Organizing Map (SOM). The SOM is an unsupervised artificial neural network that autonomously analyzes inherent dataset properties using input data only. It is typically used to cluster data into similar categories when a priori classes do not exist. The

  10. Integrating artificial neural network and classical methods for unsupervised classification of optical remote sensing data

    Science.gov (United States)

    Tahir, Ahmed AK

    2012-12-01

    A novel system named unsupervised multiple classifier system (UMCS) for unsupervised classification of optical remote sensing data is presented. The system is based on integrating two or more individual classifiers. A new dynamic selection-based method is developed for integrating the decisions of the individual classifiers. It is based on competition distance arranged in a table named class-distance map (CDM) associated to each individual classifier. These maps are derived from the class-to-class-distance measures which represent the distances between each class and the remaining classes for each individual classifier. Three individual classifiers are used for the development of the system, K-means and K-medians clustering of the classical approach and Kohonen network of the artificial neural network approach. The system is applied to ETM + images of an area North to Mosul dam in northern part of Iraq. To show the significance of increasing the number of individual classifiers, the application covered three modes, UMCS@, UMCS#, and UMCS*. In UMCS@, K-means and Kohonen are used as individual classifiers. In UMCS#, K-medians and Kohonen are used as individual classifiers. In UMCS*, K-means, K-medians and Kohonen are used as individual classifiers. The performance of the system for the three modes is evaluated by comparing the outputs of individual classifiers to the outputs of UMCSs using test data extracted by visual interpretation of color composite images. The evaluation has shown that the performance of the system with all three modes outrages the performance of the individual classifiers. However, the improvement in the class and average accuracy for UMCS* was significant compared to the improvements made by UMCS@, and UMCS#. For UMCS*, the accuracy of all classes were improved over the accuracy achieved by each of the individual classifiers and the average improvements reached (4.27, 3.70, and 6.41%) over the average accuracy achieved by K-means, K-medians and

  11. Genome Integration and Excision by a New Streptomyces Bacteriophage, ϕJoe.

    Science.gov (United States)

    Fogg, Paul C M; Haley, Joshua A; Stark, W Marshall; Smith, Margaret C M

    2017-03-01

    Bacteriophages are the source of many valuable tools for molecular biology and genetic manipulation. In Streptomyces, most DNA cloning vectors are based on serine integrase site-specific DNA recombination systems derived from phage. Because of their efficiency and simplicity, serine integrases are also used for diverse synthetic biology applications. Here, we present the genome of a new Streptomyces phage, ϕJoe, and investigate the conditions for integration and excision of the ϕJoe genome. ϕJoe belongs to the largest Streptomyces phage cluster (R4-like) and encodes a serine integrase. The attB site from Streptomyces venezuelae was used efficiently by an integrating plasmid, pCMF92, constructed using the ϕJoe int-attP locus. The attB site for ϕJoe integrase was occupied in several Streptomyces genomes, including that of S. coelicolor, by a mobile element that varies in gene content and size between host species. Serine integrases require a phage-encoded recombination directionality factor (RDF) to activate the excision reaction. The ϕJoe RDF was identified, and its function was confirmed in vivo Both the integrase and RDF were active in in vitro recombination assays. The ϕJoe site-specific recombination system is likely to be an important addition to the synthetic biology and genome engineering toolbox.IMPORTANCEStreptomyces spp. are prolific producers of secondary metabolites, including many clinically useful antibiotics. Bacteriophage-derived integrases are important tools for genetic engineering, as they enable integration of heterologous DNA into the Streptomyces chromosome with ease and high efficiency. Recently, researchers have been applying phage integrases for a variety of applications in synthetic biology, including rapid assembly of novel combinations of genes, biosensors, and biocomputing. An important requirement for optimal experimental design and predictability when using integrases, however, is the need for multiple enzymes with different

  12. Advances in environmental genomics: towards an integrated view of micro-organisms and ecosystems.

    Science.gov (United States)

    Bertin, Philippe N; Médigue, Claudine; Normand, Philippe

    2008-02-01

    Microbial genome sequencing has, for the first time, made accessible all the components needed for both the elaboration and the functioning of a cell. Associated with other global methods such as protein and mRNA profiling, genomics has considerably extended our knowledge of physiological processes and their diversity not only in human, animal and plant pathogens but also in environmental isolates. At a higher level of complexity, the so-called meta approaches have recently shown great promise in investigating microbial communities, including uncultured micro-organisms. Combined with classical methods of physico-chemistry and microbiology, these endeavours should provide us with an integrated view of how micro-organisms adapt to particular ecological niches and participate in the dynamics of ecosystems.

  13. Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets

    DEFF Research Database (Denmark)

    Swanton, C.; Larkin, J.M.; Gerlinger, M.

    2010-01-01

    RNA screens to identify and validate functionally important genomic or transcriptomic predictive biomarkers of individual drug response in patients. PREDICT's approach to predictive biomarker discovery differs from conventional associative learning approaches, which can be susceptible to the detection...... inhibitor. Through the analysis of tumour tissue derived from pre-operative renal cell carcinoma (RCC) clinical trials, the PREDICT consortium will use established and novel methods to integrate comprehensive tumour-derived genomic data with personalised tumour-derived shRNA and high throughput si......, reducing ineffective therapy in drug resistant disease, leading to improved quality of life and higher cost efficiency, which in turn should broaden patient access to beneficial therapeutics, thereby enhancing clinical outcome and cancer survival. The consortium will also establish and consolidate...

  14. Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar

    2016-01-01

    Full Text Available As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR, which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.

  15. Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Xiangjin Kang

    Full Text Available Human-induced pluripotent stem cells (iPSCs are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines", 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines", and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV, loss of heterozygosity (LOH and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic

  16. Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kang, Xiangjin; Yu, Qian; Huang, Yuling; Song, Bing; Chen, Yaoyong; Gao, Xingcheng; He, Wenyin; Sun, Xiaofang; Fan, Yong

    2015-01-01

    Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines"), 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines"), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture) database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP) calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations

  17. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Science.gov (United States)

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  18. An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results.

    Science.gov (United States)

    Carboni, Caterina; Bisoni, Lorenzo; Carta, Nicola; Puddu, Roberto; Raspopovic, Stanisa; Navarro, Xavier; Raffo, Luigi; Barbaro, Massimo

    2016-04-01

    The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35μ m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7μ V r m s , and to selectively elicit the tibial and plantar muscles using different active sites of the electrode.

  19. The effects of age, memory performance, and callosal integrity on the neural correlates of successful associative encoding.

    Science.gov (United States)

    de Chastelaine, Marianne; Wang, Tracy H; Minton, Brian; Muftuler, L Tugan; Rugg, Michael D

    2011-09-01

    This functional magnetic resonance imaging study investigated the relationship between the neural correlates of associative memory encoding, callosal integrity, and memory performance in older adults. Thirty-six older and 18 young subjects were scanned while making relational judgments on word pairs. Neural correlates of successful encoding (subsequent memory effects) were identified by contrasting the activity elicited by study pairs that were correctly identified as having been studied together with the activity elicited by pairs wrongly judged to have come from different study trials. Subsequent memory effects common to the 2 age groups were identified in several regions, including left inferior frontal gyrus and bilateral hippocampus. Negative effects (greater activity for forgotten than for remembered items) in default network regions in young subjects were reversed in the older group, and the amount of reversal correlated negatively with memory performance. Additionally, older subjects' subsequent memory effects in right frontal cortex correlated positively with anterior callosal integrity and negatively with memory performance. It is suggested that recruitment of right frontal cortex during verbal memory encoding may reflect the engagement of processes that compensate only partially for age-related neural degradation.

  20. Neural Network Combination by Fuzzy Integral for Robust Change Detection in Remotely Sensed Imagery

    OpenAIRE

    Nemmour Hassiba; Chibani Youcef

    2005-01-01

    Combining multiple neural networks has been used to improve the decision accuracy in many application fields including pattern recognition and classification. In this paper, we investigate the potential of this approach for land cover change detection. In a first step, we perform many experiments in order to find the optimal individual networks in terms of architecture and training rule. In the second step, different neural network change detectors are combined using a method based on the no...

  1. An integrated 4249 marker FISH/RH map of the canine genome

    Directory of Open Access Journals (Sweden)

    Mahairas Gregory G

    2004-09-01

    Full Text Available Abstract Background The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. Results To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH. The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS between the dog and human genomes, dramatically extending the length of most previously described CS. Conclusions These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps.

  2. Feature context-dependency and complexity-reduction in probability landscapes for integrative genomics

    Directory of Open Access Journals (Sweden)

    Benecke Arndt

    2008-09-01

    Full Text Available Abstract Background The question of how to integrate heterogeneous sources of biological information into a coherent framework that allows the gene regulatory code in eukaryotes to be systematically investigated is one of the major challenges faced by systems biology. Probability landscapes, which include as reference set the probabilistic representation of the genomic sequence, have been proposed as a possible approach to the systematic discovery and analysis of correlations amongst initially heterogeneous and un-relatable descriptions and genome-wide measurements. Much of the available experimental sequence and genome activity information is de facto, but not necessarily obviously, context dependent. Furthermore, the context dependency of the relevant information is itself dependent on the biological question addressed. It is hence necessary to develop a systematic way of discovering the context-dependency of functional genomics information in a flexible, question-dependent manner. Results We demonstrate here how feature context-dependency can be systematically investigated using probability landscapes. Furthermore, we show how different feature probability profiles can be conditionally collapsed to reduce the computational and formal, mathematical complexity of probability landscapes. Interestingly, the possibility of complexity reduction can be linked directly to the analysis of context-dependency. Conclusion These two advances in our understanding of the properties of probability landscapes not only simplify subsequent cross-correlation analysis in hypothesis-driven model building and testing, but also provide additional insights into the biological gene regulatory problems studied. Furthermore, insights into the nature of individual features and a classification of features according to their minimal context-dependency are achieved. The formal structure proposed contributes to a concrete and tangible basis for attempting to formulate novel

  3. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants

    Indian Academy of Sciences (India)

    Alice Kujur; Maneesha S Saxena; Deepak Bajaj; Laxmi; Swarup K Parida

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world’s food security. To improve the productivity and sustainability of agriculture, the development of high-yielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern –omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  4. Rice Annotation Project Database (RAP-DB): an integrative and interactive database for rice genomics.

    Science.gov (United States)

    Sakai, Hiroaki; Lee, Sung Shin; Tanaka, Tsuyoshi; Numa, Hisataka; Kim, Jungsok; Kawahara, Yoshihiro; Wakimoto, Hironobu; Yang, Ching-chia; Iwamoto, Masao; Abe, Takashi; Yamada, Yuko; Muto, Akira; Inokuchi, Hachiro; Ikemura, Toshimichi; Matsumoto, Takashi; Sasaki, Takuji; Itoh, Takeshi

    2013-02-01

    The Rice Annotation Project Database (RAP-DB, http://rapdb.dna.affrc.go.jp/) has been providing a comprehensive set of gene annotations for the genome sequence of rice, Oryza sativa (japonica group) cv. Nipponbare. Since the first release in 2005, RAP-DB has been updated several times along with the genome assembly updates. Here, we present our newest RAP-DB based on the latest genome assembly, Os-Nipponbare-Reference-IRGSP-1.0 (IRGSP-1.0), which was released in 2011. We detected 37,869 loci by mapping transcript and protein sequences of 150 monocot species. To provide plant researchers with highly reliable and up to date rice gene annotations, we have been incorporating literature-based manually curated data, and 1,626 loci currently incorporate literature-based annotation data, including commonly used gene names or gene symbols. Transcriptional activities are shown at the nucleotide level by mapping RNA-Seq reads derived from 27 samples. We also mapped the Illumina reads of a Japanese leading japonica cultivar, Koshihikari, and a Chinese indica cultivar, Guangluai-4, to the genome and show alignments together with the single nucleotide polymorphisms (SNPs) and gene functional annotations through a newly developed browser, Short-Read Assembly Browser (S-RAB). We have developed two satellite databases, Plant Gene Family Database (PGFD) and Integrative Database of Cereal Gene Phylogeny (IDCGP), which display gene family and homologous gene relationships among diverse plant species. RAP-DB and the satellite databases offer simple and user-friendly web interfaces, enabling plant and genome researchers to access the data easily and facilitating a broad range of plant research topics.

  5. Perspectives on Clinical Informatics: Integrating Large-Scale Clinical, Genomic, and Health Information for Clinical Care

    Directory of Open Access Journals (Sweden)

    In Young Choi

    2013-12-01

    Full Text Available The advances in electronic medical records (EMRs and bioinformatics (BI represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

  6. Perspectives on clinical informatics: integrating large-scale clinical, genomic, and health information for clinical care.

    Science.gov (United States)

    Choi, In Young; Kim, Tae-Min; Kim, Myung Shin; Mun, Seong K; Chung, Yeun-Jun

    2013-12-01

    The advances in electronic medical records (EMRs) and bioinformatics (BI) represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO) aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

  7. Development and clinical application of an integrative genomic approach to personalized cancer therapy.

    Science.gov (United States)

    Uzilov, Andrew V; Ding, Wei; Fink, Marc Y; Antipin, Yevgeniy; Brohl, Andrew S; Davis, Claire; Lau, Chun Yee; Pandya, Chetanya; Shah, Hardik; Kasai, Yumi; Powell, James; Micchelli, Mark; Castellanos, Rafael; Zhang, Zhongyang; Linderman, Michael; Kinoshita, Yayoi; Zweig, Micol; Raustad, Katie; Cheung, Kakit; Castillo, Diane; Wooten, Melissa; Bourzgui, Imane; Newman, Leah C; Deikus, Gintaras; Mathew, Bino; Zhu, Jun; Glicksberg, Benjamin S; Moe, Aye S; Liao, Jun; Edelmann, Lisa; Dudley, Joel T; Maki, Robert G; Kasarskis, Andrew; Holcombe, Randall F; Mahajan, Milind; Hao, Ke; Reva, Boris; Longtine, Janina; Starcevic, Daniela; Sebra, Robert; Donovan, Michael J; Li, Shuyu; Schadt, Eric E; Chen, Rong

    2016-06-01

    Personalized therapy provides the best outcome of cancer care and its implementation in the clinic has been greatly facilitated by recent convergence of enormous progress in basic cancer research, rapid advancement of new tumor profiling technologies, and an expanding compendium of targeted cancer therapeutics. We developed a personalized cancer therapy (PCT) program in a clinical setting, using an integrative genomics approach to fully characterize the complexity of each tumor. We carried out whole exome sequencing (WES) and single-nucleotide polymorphism (SNP) microarray genotyping on DNA from tumor and patient-matched normal specimens, as well as RNA sequencing (RNA-Seq) on available frozen specimens, to identify somatic (tumor-specific) mutations, copy number alterations (CNAs), gene expression changes, gene fusions, and also germline variants. To provide high sensitivity in known cancer mutation hotspots, Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2) was also employed. We integrated the resulting data with cancer knowledge bases and developed a specific workflow for each cancer type to improve interpretation of genomic data. We returned genomics findings to 46 patients and their physicians describing somatic alterations and predicting drug response, toxicity, and prognosis. Mean 17.3 cancer-relevant somatic mutations per patient were identified, 13.3-fold, 6.9-fold, and 4.7-fold more than could have been detected using CHPv2, Oncomine Cancer Panel (OCP), and FoundationOne, respectively. Our approach delineated the underlying genetic drivers at the pathway level and provided meaningful predictions of therapeutic efficacy and toxicity. Actionable alterations were found in 91 % of patients (mean 4.9 per patient, including somatic mutations, copy number alterations, gene expression alterations, and germline variants), a 7.5-fold, 2.0-fold, and 1.9-fold increase over what could have been uncovered by CHPv2, OCP, and FoundationOne, respectively. The findings altered

  8. Integrating resource defence theory with a neural nonapeptide pathway to explain territory-based mating systems.

    Science.gov (United States)

    Oldfield, Ronald G; Harris, Rayna M; Hofmann, Hans A

    2015-01-01

    The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom.

  9. INDIGO – INtegrated Data Warehouse of MIcrobial GenOmes with Examples from the Red Sea Extremophiles

    Science.gov (United States)

    Alam, Intikhab; Antunes, André; Kamau, Allan Anthony; Ba alawi, Wail; Kalkatawi, Manal; Stingl, Ulrich; Bajic, Vladimir B.

    2013-01-01

    Background The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. Results We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. Conclusions We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo. PMID

  10. MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes.

    Science.gov (United States)

    Vallenet, David; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Lajus, Aurélie; Josso, Adrien; Mercier, Jonathan; Renaux, Alexandre; Rollin, Johan; Rouy, Zoe; Roche, David; Scarpelli, Claude; Médigue, Claudine

    2017-01-04

    The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes

    Science.gov (United States)

    Vallenet, David; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Lajus, Aurélie; Josso, Adrien; Mercier, Jonathan; Renaux, Alexandre; Rollin, Johan; Rouy, Zoe; Roche, David; Scarpelli, Claude; Médigue, Claudine

    2017-01-01

    The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations. PMID:27899624

  12. Accurate Localization of the Integration Sites of Two Genomic Islands at Single-Nucleotide Resolution in the Genome of Bacillus cereus ATCC 10987

    Directory of Open Access Journals (Sweden)

    Ren Zhang

    2008-01-01

    Full Text Available We have identified two genomic islands, that is, BCEGI-1 and BCEGI-2, in the genome of Bacillus cereus ATCC 10987, based on comparative analysis with Bacillus cereus ATCC 14579. Furthermore, by using the cumulative GC profile and performing homology searches between the two genomes, the integration sites of the two genomic islands were determined at single-nucleotide resolution. BCEGI-1 is integrated between 159705 bp and 198000 bp, whereas BCEGI-2 is integrated between the end of ORF BCE4594 and the start of the intergenic sequence immediately following BCE4626, that is, from 4256803 bp to 4285534 bp. BCEGI-1 harbors two bacterial Tn7 transposons, which have two sets of genes encoding TnsA, B, C, and D. It is generally believed that unlike the TnsABC+E pathway, the TnsABC+D pathway would only promote vertical transmission to daughter cells. The evidence presented in this paper, however, suggests a role of the TnsABC+D pathway in the horizontal transfer of some genomic islands.

  13. Functionally integrated neural processing of linguistic and talker information: An event-related fMRI and ERP study.

    Science.gov (United States)

    Zhang, Caicai; Pugh, Kenneth R; Mencl, W Einar; Molfese, Peter J; Frost, Stephen J; Magnuson, James S; Peng, Gang; Wang, William S-Y

    2016-01-01

    Speech signals contain information of both linguistic content and a talker's voice. Conventionally, linguistic and talker processing are thought to be mediated by distinct neural systems in the left and right hemispheres respectively, but there is growing evidence that linguistic and talker processing interact in many ways. Previous studies suggest that talker-related vocal tract changes are processed integrally with phonetic changes in the bilateral posterior superior temporal gyrus/superior temporal sulcus (STG/STS), because the vocal tract parameter influences the perception of phonetic information. It is yet unclear whether the bilateral STG is also activated by the integral processing of another parameter - pitch, which influences the perception of lexical tone information and is related to talker differences in tone languages. In this study, we conducted separate functional magnetic resonance imaging (fMRI) and event-related potential (ERP) experiments to examine the spatial and temporal loci of interactions of lexical tone and talker-related pitch processing in Cantonese. We found that the STG was activated bilaterally during the processing of talker changes when listeners attended to lexical tone changes in the stimuli and during the processing of lexical tone changes when listeners attended to talker changes, suggesting that lexical tone and talker processing are functionally integrated in the bilateral STG. It extends the previous study, providing evidence for a general neural mechanism of integral phonetic and talker processing in the bilateral STG. The ERP results show interactions of lexical tone and talker processing 500-800ms after auditory word onset (a simultaneous posterior P3b and a frontal negativity). Moreover, there is some asymmetry in the interaction, such that unattended talker changes affect linguistic processing more than vice versa, which may be related to the ambiguity that talker changes cause in speech perception and/or attention bias

  14. A neural systems-based neurobiology and neuropsychiatry course: integrating biology, psychodynamics, and psychology in the psychiatric curriculum.

    Science.gov (United States)

    Lacy, Timothy; Hughes, John D

    2006-01-01

    Psychotherapy and biological psychiatry remain divided in psychiatry residency curricula. Behavioral neurobiology and neuropsychiatry provide a systems-level framework that allows teachers to integrate biology, psychodynamics, and psychology. The authors detail the underlying assumptions and outline of a neural systems-based neuroscience course they teach at the National Capital Consortium Psychiatry Residency Program. They review course assessment reports and classroom observations. Self-report measures and teacher observations are encouraging. By the end of the course, residents are able to discuss both neurobiological and psychodynamic/psychological concepts of distributed biological neural networks. They verbalize an understanding that psychology is biology, that any distinction is artificial, and that both are valuable. A neuroscience curriculum founded on the underlying principles of behavioral neurobiology and neuropsychiatry is inherently anti-reductionistic and facilitates the acquisition of detailed information as well as critical thinking and cross-disciplinary correlations with psychological theories and psychotherapy.

  15. Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration.

    Directory of Open Access Journals (Sweden)

    Aviad Levin

    Full Text Available BACKGROUND: The human immunodeficiency virus type 1 (HIV-1 integrase protein (IN, catalyzes the integration of viral DNA into the host cell genome. IN catalyzes the first step of the integration process, namely the 3'-end processing in which IN removes a pGT dinucleotide from the 3' end of each viral long terminal repeat (LTR. Following nuclear import of the viral preintegration complex, the host chromosomal DNA becomes accessible to the viral cDNA and the second step of the integration process, namely the strand-transfer step takes place. This ordered sequence of events, centered on integration, is mandatory for HIV replication. METHODOLOGY/PRINCIPAL FINDINGS: Using an integrase peptide library, we selected two peptides, designated INr-1 and INr-2, which interact with the Rev protein and probably mediate the Rev-integrase interaction. Using an in-vitro assay system, we show that INr-1 and INr-2 are able to abrogate the inhibitory effects exerted by Rev and Rev-derived peptides on integrase activity. Both INr-1 and INr-2 were found to be cell-permeable and nontoxic, allowing a study of their effect in HIV-1-infected cultured cells. Interestingly, both INr peptides stimulated virus infectivity as estimated by production of the viral P24 protein, as well as by determination of the appearance of newly formed virus particles. Furthermore, kinetics studies revealed that the cell-permeable INr peptides enhance the integration process, as was indeed confirmed by direct determination of viral DNA integration by real-time PCR. CONCLUSIONS/SIGNIFICANCE: The results of the present study raise the possibility that in HIV-infected cells, the Rev protein may be involved in the integration of proviral DNA by controlling/regulating the activity of the integrase. Release from such inhibition leads to stimulation of IN activity and multiple viral DNA integration events.

  16. A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for canine cancer studies and comparative genomic analysis.

    Science.gov (United States)

    Thomas, R; Duke, S E; Karlsson, E K; Evans, A; Ellis, P; Lindblad-Toh, K; Langford, C F; Breen, M

    2008-01-01

    Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.

  17. Conjugative Transfer and cis-Mobilization of a Genomic Island by an Integrative and Conjugative Element of Streptococcus agalactiae

    OpenAIRE

    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie

    2013-01-01

    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913–6917, 2008). We investigated here the mobility of the elements integrated into the 3′ end of a tRNALys gene. Three of the four putative ICEs tested were found to ...

  18. Improving biological understanding and complex trait prediction by integrating prior information in genomic feature models

    DEFF Research Database (Denmark)

    Edwards, Stefan McKinnon

    externally founded information, such as KEGG pathways, Gene Ontology gene sets, or genomic features, and estimate the joint contribution of the genetic variants within these sets to complex trait phenotypes. The analysis of complex trait phenotypes is hampered by the myriad of genes that control the trait......In this thesis we investigate an approach to integrate external data into the analysis of genetic variants. The goal is similar to that of gene-set enrichment tests, but relies on the robust statistical framework of linear mixed models. This approach has allowed us to integrate virtually any......, as these genes have small to moderate effects that can be difficult to detect. However, by looking at sets of genes, as in gene-set enrichment tests, it may become easier to assess an association between the set of genes and the complex trait. ---  The linear mixed models applied here are the same as used...

  19. Genome scale models of yeast: towards standardized evaluation and consistent omic integration

    DEFF Research Database (Denmark)

    Sanchez, Benjamin J.; Nielsen, Jens

    2015-01-01

    Genome scale models (GEMs) have enabled remarkable advances in systems biology, acting as functional databases of metabolism, and as scaffolds for the contextualization of high-throughput data. In the case of Saccharomyces cerevisiae (budding yeast), several GEMs have been published...... and are currently used for metabolic engineering and elucidating biological interactions. Here we review the history of yeast's GEMs, focusing on recent developments. We study how these models are typically evaluated, using both descriptive and predictive metrics. Additionally, we analyze the different ways...... in which all levels of omics data (from gene expression to flux) have been integrated in yeast GEMs. Relevant conclusions and current challenges for both GEM evaluation and omic integration are highlighted....

  20. Integration of gene expression data into genome-scale metabolic models

    DEFF Research Database (Denmark)

    Åkesson, M.; Förster, Jochen; Nielsen, Jens

    2004-01-01

    of gene expression from chemostat and batch cultures of Saccharomyces cerevisiae were combined with a recently developed genome-scale model, and the computed metabolic flux distributions were compared to experimental values from carbon labeling experiments and metabolic network analysis. The integration......A framework for integration of transcriptome data into stoichiometric metabolic models to obtain improved flux predictions is presented. The key idea is to exploit the regulatory information in the expression data to give additional constraints on the metabolic fluxes in the model. Measurements...... of expression data resulted in improved predictions of metabolic behavior in batch cultures, enabling quantitative predictions of exchange fluxes as well as qualitative estimations of changes in intracellular fluxes. A critical discussion of correlation between gene expression and metabolic fluxes is given....

  1. Application of integrative genomics and systems biology to conventional and in vitro reproductive traits in cattle

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Pedersen, Hanne S.; de Oliveira Junior, Gerson A.

    2017-01-01

    by both conventional and ARTs such as OPU-IVP. The integration of systems biology information across different biological layers generates a complete view of the different molecular networks that control complex traits and can provide a strong contribution to the understanding of traits related to ARTs....... donor and embryo recipient quality is needed to make realistic a commercialization of these procedures in the near future. A better understanding of both biological mechanisms and molecular markers associated to IVPET related traits is necessary to improve the prediction of donor and recipient cow...... quality for IVP procedures. The huge amount of data generated from high throughput technologies has a tremendous impact in the search for biomarkers of complex traits. This paper reviews integrative genomics and systems biology approaches as applied to both Bos indicus and Bos taurus cattle reproduction...

  2. Integration of transcriptome and whole genomic resequencing data to identify key genes affecting swine fat deposition.

    Directory of Open Access Journals (Sweden)

    Kai Xing

    Full Text Available Fat deposition is highly correlated with the growth, meat quality, reproductive performance and immunity of pigs. Fatty acid synthesis takes place mainly in the adipose tissue of pigs; therefore, in this study, a high-throughput massively parallel sequencing approach was used to generate adipose tissue transcriptomes from two groups of Songliao black pigs that had opposite backfat thickness phenotypes. The total number of paired-end reads produced for each sample was in the range of 39.29-49.36 millions. Approximately 188 genes were differentially expressed in adipose tissue and were enriched for metabolic processes, such as fatty acid biosynthesis, lipid synthesis, metabolism of fatty acids, etinol, caffeine and arachidonic acid and immunity. Additionally, many genetic variations were detected between the two groups through pooled whole-genome resequencing. Integration of transcriptome and whole-genome resequencing data revealed important genomic variations among the differentially expressed genes for fat deposition, for example, the lipogenic genes. Further studies are required to investigate the roles of candidate genes in fat deposition to improve pig breeding programs.

  3. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

    OpenAIRE

    Barnes, Ryan; Eckert, Kristin

    2017-01-01

    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome ...

  4. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Bekim Sadikovic

    Full Text Available Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks.

  5. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

    Science.gov (United States)

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  6. Purdue Ionomics Information Management System. An Integrated Functional Genomics Platform1[C][W][OA

    Science.gov (United States)

    Baxter, Ivan; Ouzzani, Mourad; Orcun, Seza; Kennedy, Brad; Jandhyala, Shrinivas S.; Salt, David E.

    2007-01-01

    The advent of high-throughput phenotyping technologies has created a deluge of information that is difficult to deal with without the appropriate data management tools. These data management tools should integrate defined workflow controls for genomic-scale data acquisition and validation, data storage and retrieval, and data analysis, indexed around the genomic information of the organism of interest. To maximize the impact of these large datasets, it is critical that they are rapidly disseminated to the broader research community, allowing open access for data mining and discovery. We describe here a system that incorporates such functionalities developed around the Purdue University high-throughput ionomics phenotyping platform. The Purdue Ionomics Information Management System (PiiMS) provides integrated workflow control, data storage, and analysis to facilitate high-throughput data acquisition, along with integrated tools for data search, retrieval, and visualization for hypothesis development. PiiMS is deployed as a World Wide Web-enabled system, allowing for integration of distributed workflow processes and open access to raw data for analysis by numerous laboratories. PiiMS currently contains data on shoot concentrations of P, Ca, K, Mg, Cu, Fe, Zn, Mn, Co, Ni, B, Se, Mo, Na, As, and Cd in over 60,000 shoot tissue samples of Arabidopsis (Arabidopsis thaliana), including ethyl methanesulfonate, fast-neutron and defined T-DNA mutants, and natural accession and populations of recombinant inbred lines from over 800 separate experiments, representing over 1,000,000 fully quantitative elemental concentrations. PiiMS is accessible at www.purdue.edu/dp/ionomics. PMID:17189337

  7. Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol.

    Science.gov (United States)

    Bubier, Jason A; Wilcox, Troy D; Jay, Jeremy J; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

    2016-01-01

    Identifying the biological substrates of complex neurobehavioral traits such as alcohol dependency pose a tremendous challenge given the diverse model systems and phenotypic assessments used. To address this problem we have developed a platform for integrated analysis of high-throughput or genome-wide functional genomics studies. A wealth of such data exists, but it is often found in disparate, non-computable forms. Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis. Using this system we identified a gene underlying multiple alcohol-related phenotypes in four species. A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol-related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains. We identified highly connected genes and compared these to genes currently annotated to alcohol-related behaviors and processes. The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with an increased preference for alcohol and an altered thermoregulatory response to alcohol. Although this gene has not been previously implicated in alcohol-related behaviors, its function in various neural mechanisms makes a role in alcohol-related phenomena plausible. By making diverse cross-species functional genomics data readily computable, we were able to identify and confirm a novel alcohol-related gene that may have implications for alcohol use disorders and other effects of alcohol.

  8. Multi-sensor integration for on-line tool wear estimation through radial basis function networks and fuzzy neural network.

    Science.gov (United States)

    Kuo, R J.; Cohen, P H.

    1999-03-01

    On-line tool wear estimation plays a very critical role in industry automation for higher productivity and product quality. In addition, appropriate and timely decision for tool change is significantly required in the machining systems. Thus, this paper is dedicated to develop an estimation system through integration of two promising technologies, artificial neural networks (ANN) and fuzzy logic. An on-line estimation system consisting of five components: (1) data collection; (2) feature extraction; (3) pattern recognition; (4) multi-sensor integration; and (5) tool/work distance compensation for tool flank wear, is proposed herein. For each sensor, a radial basis function (RBF) network is employed to recognize the extracted features. Thereafter, the decisions from multiple sensors are integrated through a proposed fuzzy neural network (FNN) model. Such a model is self-organizing and self-adjusting, and is able to learn from the experience. Physical experiments for the metal cutting process are implemented to evaluate the proposed system. The results show that the proposed system can significantly increase the accuracy of the product profile.

  9. A multichannel integrated circuit for neural spike detection based on EC-PC threshold estimation.

    Science.gov (United States)

    Wu, Tong; Yang, Zhi

    2013-01-01

    In extracellular neural recording experiments, spike detection is an important step for information decoding of neuronal activities. An ASIC implementation of detection algorithms can provide substantial data-rate reduction and facilitate wireless operations. In this paper, we present a 16-channel neural spike detection ASIC. The chip takes raw data as inputs, and outputs three data streams simultaneously: field potentials down sampled at 1.25 KHz, band-pass filtered neural data, and spiking probability maps sampled at 40 KHz. The functionality and the performance of the chip have been verified in both in-vivo and benchtop experiments. Fabricated in a 0.13 µm CMOS process, the chip has a peak power dissipation of 85 µW per channel and achieves a data-rate reduction of 98.44%.

  10. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Science.gov (United States)

    van der Lee, Robin; Feng, Qian; Langereis, Martijn A; Ter Horst, Rob; Szklarczyk, Radek; Netea, Mihai G; Andeweg, Arno C; van Kuppeveld, Frank J M; Huynen, Martijn A

    2015-10-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50%) that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1), and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1). Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/), obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

  11. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2015-10-01

    Full Text Available The RIG-I-like receptor (RLR pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50% that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1, and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1. Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/, obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

  12. An integrated framework for discovery and genotyping of genomic variants from high-throughput sequencing experiments.

    Science.gov (United States)

    Duitama, Jorge; Quintero, Juan Camilo; Cruz, Daniel Felipe; Quintero, Constanza; Hubmann, Georg; Foulquié-Moreno, Maria R; Verstrepen, Kevin J; Thevelein, Johan M; Tohme, Joe

    2014-04-01

    Recent advances in high-throughput sequencing (HTS) technologies and computing capacity have produced unprecedented amounts of genomic data that have unraveled the genetics of phenotypic variability in several species. However, operating and integrating current software tools for data analysis still require important investments in highly skilled personnel. Developing accurate, efficient and user-friendly software packages for HTS data analysis will lead to a more rapid discovery of genomic elements relevant to medical, agricultural and industrial applications. We therefore developed Next-Generation Sequencing Eclipse Plug-in (NGSEP), a new software tool for integrated, efficient and user-friendly detection of single nucleotide variants (SNVs), indels and copy number variants (CNVs). NGSEP includes modules for read alignment, sorting, merging, functional annotation of variants, filtering and quality statistics. Analysis of sequencing experiments in yeast, rice and human samples shows that NGSEP has superior accuracy and efficiency, compared with currently available packages for variants detection. We also show that only a comprehensive and accurate identification of repeat regions and CNVs allows researchers to properly separate SNVs from differences between copies of repeat elements. We expect that NGSEP will become a strong support tool to empower the analysis of sequencing data in a wide range of research projects on different species.

  13. Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes

    Indian Academy of Sciences (India)

    Indraneel Mittra; Naveen Kumar Khare; Gorantla Venkata Raghuram; Rohan Chaubal; Fatema Khambatti; Deepika Gupta; Ashwini Gaikwad; Preeti Prasannan; Akshita Singh; Aishwarya Iyer; Ankita Singh; Pawan Upadhyay; Naveen Kumar Nair; Pradyumna Kumar Mishra; Amit Dutt

    2015-03-01

    Whether nucleic acids that circulate in blood have any patho-physiological functions in the host have not been explored. We report here that far from being inert molecules, circulating nucleic acids have significant biological activities of their own that are deleterious to healthy cells of the body. Fragmented DNA and chromatin (DNAfs and Cfs) isolated from blood of cancer patients and healthy volunteers are readily taken up by a variety of cells in culture to be localized in their nuclei within a few minutes. The intra-nuclear DNAfs and Cfs associate themselves with host cell chromosomes to evoke a cellular DNA-damage-repair-response (DDR) followed by their incorporation into the host cell genomes. Whole genome sequencing detected the presence of tens of thousands of human sequence reads in the recipient mouse cells. Genomic incorporation of DNAfs and Cfs leads to dsDNA breaks and activation of apoptotic pathways in the treated cells. When injected intravenously into Balb/C mice, DNAfs and Cfs undergo genomic integration into cells of their vital organs resulting in activation of DDR and apoptotic proteins in the recipient cells. Cfs have significantly greater activity than DNAfs with respect to all parameters examined, while both DNAfs and Cfs isolated from cancer patients are more active than those from normal volunteers. All the above pathological actions of DNAfs and Cfs described above can be abrogated by concurrent treatment with DNase I and/or anti-histone antibody complexed nanoparticles both in vitro and in vivo. Taken together, our results that circulating DNAfs and Cfs are physiological, continuously arising, endogenous DNA damaging agents with implications to ageing and a multitude of human pathologies including initiation of cancer.

  14. Genetic control of flowering time in rice: integration of Mendelian genetics and genomics.

    Science.gov (United States)

    Hori, Kiyosumi; Matsubara, Kazuki; Yano, Masahiro

    2016-12-01

    Integration of previous Mendelian genetic analyses and recent molecular genomics approaches, such as linkage mapping and QTL cloning, dramatically strengthened our current understanding of genetic control of rice flowering time. Flowering time is one of the most important agronomic traits for seed production in rice (Oryza sativa L.). It is controlled mainly by genes associated with photoperiod sensitivity, particularly in short-day plants such as rice. Since the early twentieth century, rice breeders and researchers have been interested in elucidating the genetic basis of flowering time because its modification is important for regional adaptation and yield optimization. Although flowering time is a complex trait controlled by many quantitative trait loci (QTLs), classical genetic studies have shown that many associated genes are inherited in accordance with Mendelian laws. Decoding the rice genome sequence opened a new era in understanding the genetic control of flowering time on the basis of genome-wide mapping and gene cloning. Heading date 1 (Hd1) was the first flowering time QTL to be isolated using natural variation in rice. Recent accumulation of information on rice genome has facilitated the cloning of other QTLs, including those with minor effects on flowering time. This information has allowed us to rediscover some of the flowering genes that were identified by classical Mendelian genetics. The genes characterized so far, including Hd1, have been assigned to specific photoperiod pathways. In this review, we provide an overview of the studies that led to an in-depth understanding of the genetic control of flowering time in rice, and of the current state of improving and fine-tuning this trait for rice breeding.

  15. PSA-NCAM(+) neural precursor cells from human embryonic stem cells promote neural tissue integrity and behavioral performance in a rat stroke model.

    Science.gov (United States)

    Kim, Han-Soo; Choi, Seong-Mi; Yang, Wonsuk; Kim, Dae-Sung; Lee, Dongjin R; Cho, Sung-Rae; Kim, Dong-Wook

    2014-12-01

    Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPC(PSA-NCAM+)) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPC(PSA-NCAM+) are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPC(PSA-NCAM+). Unlike MSCs, NPC(PSA-NCAM+) demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPC(PSA-NCAM+) evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPC(PSA-NCAM+) elevated α-SMA(+) immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPC(PSA-NCAM+) preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPC(PSA-NCAM+) as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke.

  16. An integrative genomic and epigenomic approach for the study of transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Maria E Figueroa

    Full Text Available The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis and developing new targeted-therapies. Aberrant gene regulation is a hallmark of cancer and plays a central role in determining tumor phenotype. We predicted that integration of different genome-wide epigenetic regulatory marks along with gene expression levels would provide greater power in capturing biological differences between leukemia subtypes. Gene expression, cytosine methylation and histone H3 lysine 9 (H3K9 acetylation were measured using high-density oligonucleotide microarrays in primary human acute myeloid leukemia (AML and acute lymphocytic leukemia (ALL specimens. We found that DNA methylation and H3K9 acetylation distinguished these leukemias of distinct cell lineage, as expected, but that an integrative analysis combining the information from each platform revealed hundreds of additional differentially expressed genes that were missed by gene expression arrays alone. This integrated analysis also enhanced the detection and statistical significance of biological pathways dysregulated in AML and ALL. Integrative epigenomic studies are thus feasible using clinical samples and provide superior detection of aberrant transcriptional programming than single-platform microarray studies.

  17. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  18. Spectrum of the nonstationary electromyographic signal modelled with integral pulse frequency modulation and its application to estimating neural drive information.

    Science.gov (United States)

    Jiang, Ning; Parker, Philip A; Englehart, Kevin B

    2009-08-01

    The spectrum of nonstationary electromyographic signal (EMG) is investigated, from which the error for neural drive information estimation from nonstationary EMG is studied in terms of signal-to-noise ratio (SNR), in analytical, numerical simulation, and experimental work. The signal refers to the neural drive information embedded within the nonstationary EMG, and noise refers to other portions of EMG that induce error in the estimation. The analytical expressions for the SNRs of force-modulated EMG with both single and multiple motor units (MU) are derived based on a sinusoidal integral pulse frequency modulation (IPFM) model. It is shown that the previously developed SNR expressions for stationary (unmodulated) EMG are special cases of the formulas presented here. The SNR results obtained from numerical simulated EMG agree very well with the analytical result. Results from nonstationary (modulated) surface EMG obtained from seven subjects also match the analytical and simulation results reasonably well. The results obtained from this work establish an analytical framework in studying and estimating the neural drive information contained in the EMG in the context of anisotonic and isometric contractions. Through the analytical study, the effects of different physiological parameters are identified, thus providing theoretical guidelines for developing advanced signal processing methods for nonstationary EMG in applications such as prosthesis control.

  19. Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis.

    Science.gov (United States)

    Wang, Linlin; Lin, Shanshan; Zhang, Ji; Tian, Tian; Jin, Lei; Ren, Aiguo

    2017-02-01

    Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

  20. Genome-wide conserved non-coding microsatellite (CNMS) marker-based integrative genetical genomics for quantitative dissection of seed weight in chickpea

    Science.gov (United States)

    Bajaj, Deepak; Saxena, Maneesha S.; Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Tripathi, Shailesh; Upadhyaya, Hari D.; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    Phylogenetic footprinting identified 666 genome-wide paralogous and orthologous CNMS (conserved non-coding microsatellite) markers from 5′-untranslated and regulatory regions (URRs) of 603 protein-coding chickpea genes. The (CT)n and (GA)n CNMS carrying CTRMCAMV35S and GAGA8BKN3 regulatory elements, respectively, are abundant in the chickpea genome. The mapped genic CNMS markers with robust amplification efficiencies (94.7%) detected higher intraspecific polymorphic potential (37.6%) among genotypes, implying their immense utility in chickpea breeding and genetic analyses. Seventeen differentially expressed CNMS marker-associated genes showing strong preferential and seed tissue/developmental stage-specific expression in contrasting genotypes were selected to narrow down the gene targets underlying seed weight quantitative trait loci (QTLs)/eQTLs (expression QTLs) through integrative genetical genomics. The integration of transcript profiling with seed weight QTL/eQTL mapping, molecular haplotyping, and association analyses identified potential molecular tags (GAGA8BKN3 and RAV1AAT regulatory elements and alleles/haplotypes) in the LOB-domain-containing protein- and KANADI protein-encoding transcription factor genes controlling the cis-regulated expression for seed weight in the chickpea. This emphasizes the potential of CNMS marker-based integrative genetical genomics for the quantitative genetic dissection of complex seed weight in chickpea. PMID:25504138

  1. OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

    Directory of Open Access Journals (Sweden)

    John Orechia

    2015-09-01

    Full Text Available We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS and a suite of tools called Oncology Data Retrieval Systems (OncDRS. OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies.

  2. AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

    Science.gov (United States)

    Martin, Olivier; Valsesia, Armand; Telenti, Amalio; Xenarios, Ioannis; Stevenson, Brian J

    2009-03-01

    We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

  3. Explicitly integrating parameter, input, and structure uncertainties into Bayesian Neural Networks for probabilistic hydrologic forecasting

    KAUST Repository

    Zhang, Xuesong

    2011-11-01

    Estimating uncertainty of hydrologic forecasting is valuable to water resources and other relevant decision making processes. Recently, Bayesian Neural Networks (BNNs) have been proved powerful tools for quantifying uncertainty of streamflow forecasting. In this study, we propose a Markov Chain Monte Carlo (MCMC) framework (BNN-PIS) to incorporate the uncertainties associated with parameters, inputs, and structures into BNNs. This framework allows the structure of the neural networks to change by removing or adding connections between neurons and enables scaling of input data by using rainfall multipliers. The results show that the new BNNs outperform BNNs that only consider uncertainties associated with parameters and model structures. Critical evaluation of posterior distribution of neural network weights, number of effective connections, rainfall multipliers, and hyper-parameters shows that the assumptions held in our BNNs are not well supported. Further understanding of characteristics of and interactions among different uncertainty sources is expected to enhance the application of neural networks for uncertainty analysis of hydrologic forecasting. © 2011 Elsevier B.V.

  4. Identification and integration of sensory modalities: Neural basis and relation to consciousness

    NARCIS (Netherlands)

    Pennartz, C.M.A.

    2009-01-01

    A key question in studying consciousness is how neural operations in the brain can identify streams of sensory input as belonging to distinct modalities, which contributes to the representation of qualitatively different experiences. The basis for identification of modalities is proposed to be const

  5. parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube.

    Science.gov (United States)

    Lele, Zsolt; Folchert, Anja; Concha, Miguel; Rauch, Gerd-Jörg; Geisler, Robert; Rosa, Frédéric; Wilson, Steve W; Hammerschmidt, Matthias; Bally-Cuif, Laure

    2002-07-01

    N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute (pac) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n-cadherin (ncad) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion is altered, and convergent cell movements during neurulation are severely compromised. In addition, many neurons become progressively displaced along the dorsoventral and the anteroposterior axes. At the cellular level, loss of Ncad affects beta-catenin stabilization/localization and causes mispositioned and increased mitoses in the dorsal midbrain and hindbrain, a phenotype later correlated with enhanced apoptosis and the appearance of ectopic neurons in these areas. Our results thus highlight novel and crucial in vivo roles for Ncad in the control of cell convergence, maintenance of neuronal positioning and dorsal cell proliferation during vertebrate neural tube development.

  6. Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma

    Science.gov (United States)

    Shao, Chunbo; Sun, Wenyue; Tan, Marietta; Glazer, Chad A.; Bhan, Sheetal; Zhong, Xiaoli; Fakhry, Carole; Sharma, Rajni; Westra, William H.; Hoque, Mohammad O.; Moskaluk, Christopher A.; Sidransky, David; Califano, Joseph A.; Ha, Patrick K.

    2011-01-01

    Purpose Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy that is poorly understood. In order to look for relevant oncogene candidates under the control of promoter methylation, an integrated, genome-wide screen was performed. Experimental Design Global demethylation of normal salivary gland cell strains using 5-aza-2′-deoxycytidine (5-Aza dC) and Trichostatin A (TSA), followed by expression array analysis was performed. ACC-specific expression profiling was generated using expression microarray analysis of primary ACC and normal samples. Next, the two profiles were integrated to identify a subset of genes for further validation of promoter demethylation in ACC versus normal. Finally, promising candidates were further validated for mRNA, protein, and promoter methylation levels in larger ACC cohorts. Functional validation was then performed in cancer cell lines. Results We found 159 genes that were significantly re-expressed after 5-Aza dC/TSA treatment and overexpressed in ACC. After initial validation, eight candidates showed hypomethylation in ACC: AQP1, CECR1, C1QR1, CTAG2, P53AIP1, TDRD12, BEX1, and DYNLT3. Aquaporin 1 (AQP1) showed the most significant hypomethylation and was further validated. AQP1 hypomethylation in ACC was confirmed with two independent cohorts. Of note, there was significant overexpression of AQP1 in both mRNA and protein in the paraffin-embedded ACC cohort. Furthermore, AQP1 was up-regulated in 5-Aza dC/TSA treated SACC83. Lastly, AQP1 promoted cell proliferation and colony formation in SACC83. Conclusions Our integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC. AQP1 is a promising oncogene candidate for ACC and is transcriptionally regulated by promoter hypomethylation. PMID:21551254

  7. Hybrid information privacy system: integration of chaotic neural network and RSA coding

    Science.gov (United States)

    Hsu, Ming-Kai; Willey, Jeff; Lee, Ting N.; Szu, Harold H.

    2005-03-01

    Electronic mails are adopted worldwide; most are easily hacked by hackers. In this paper, we purposed a free, fast and convenient hybrid privacy system to protect email communication. The privacy system is implemented by combining private security RSA algorithm with specific chaos neural network encryption process. The receiver can decrypt received email as long as it can reproduce the specified chaos neural network series, so called spatial-temporal keys. The chaotic typing and initial seed value of chaos neural network series, encrypted by the RSA algorithm, can reproduce spatial-temporal keys. The encrypted chaotic typing and initial seed value are hidden in watermark mixed nonlinearly with message media, wrapped with convolution error correction codes for wireless 3rd generation cellular phones. The message media can be an arbitrary image. The pattern noise has to be considered during transmission and it could affect/change the spatial-temporal keys. Since any change/modification on chaotic typing or initial seed value of chaos neural network series is not acceptable, the RSA codec system must be robust and fault-tolerant via wireless channel. The robust and fault-tolerant properties of chaos neural networks (CNN) were proved by a field theory of Associative Memory by Szu in 1997. The 1-D chaos generating nodes from the logistic map having arbitrarily negative slope a = p/q generating the N-shaped sigmoid was given first by Szu in 1992. In this paper, we simulated the robust and fault-tolerance properties of CNN under additive noise and pattern noise. We also implement a private version of RSA coding and chaos encryption process on messages.

  8. An integral term adaptive neural control of fed-batch fermentation biotechnological process; Control neuronal adaptable con termino integral para un proceso biotecnologico de fermentacion por lote alimentado

    Energy Technology Data Exchange (ETDEWEB)

    Baruch, Ieroham; Hernandez, Luis Alberto; Barrera Cortes, Josefina [Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Mexico D.F. (Mexico)

    2005-07-15

    A nonlinear mathematical model of aerobic biotechnological process of a fed-batch fermentation system is derived using ordinary differential equations. A neurocontrol is applied using Recurrent Trainable Neural Network (RTNN) plus integral term; the first network performs an approximation of the plant's output; the second network generates the control signal so that the biomass concentration could be regulated by the nutrient influent flow rate into the bioreactor. [Spanish] Un modelo matematico no lineal de un proceso biotecnologico aerobio de un sistema de fermentacion por lote alimentado es presentado mediante ecuaciones diferenciales ordinarias. Es propuesto un control utilizando dos redes neuronales recurrentes entrenables (RNRE) con la adicion de un termino integral; la primera red representa un aproximador de la salida de la planta y la segunda genera la senal de control tal que la concentracion de la biomasa pueda ser regulada mediante la alimentacion de un flujo con nutrientes al biorreactor.

  9. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

    Directory of Open Access Journals (Sweden)

    Ryan Barnes

    2017-01-01

    Full Text Available Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize “difficult to replicate” genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  10. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases.

    Science.gov (United States)

    Barnes, Ryan; Eckert, Kristin

    2017-01-06

    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize "difficult to replicate" genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  11. Genomic paradigms for food-borne enteric pathogen analysis at the USFDA: case studies highlighting method utility, integration and resolution.

    Science.gov (United States)

    Elkins, C A; Kotewicz, M L; Jackson, S A; Lacher, D W; Abu-Ali, G S; Patel, I R

    2013-01-01

    Modern risk control and food safety practices involving food-borne bacterial pathogens are benefiting from new genomic technologies for rapid, yet highly specific, strain characterisations. Within the United States Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition (CFSAN), optical genome mapping and DNA microarray genotyping have been used for several years to quickly assess genomic architecture and gene content, respectively, for outbreak strain subtyping and to enhance retrospective trace-back analyses. The application and relative utility of each method varies with outbreak scenario and the suspect pathogen, with comparative analytical power enhanced by database scale and depth. Integration of these two technologies allows high-resolution scrutiny of the genomic landscapes of enteric food-borne pathogens with notable examples including Shiga toxin-producing Escherichia coli (STEC) and Salmonella enterica serovars from a variety of food commodities. Moreover, the recent application of whole genome sequencing technologies to food-borne pathogen outbreaks and surveillance has enhanced resolution to the single nucleotide scale. This new wealth of sequence data will support more refined next-generation custom microarray designs, targeted re-sequencing and "genomic signature recognition" approaches involving a combination of genes and single nucleotide polymorphism detection to distil strain-specific fingerprinting to a minimised scale. This paper examines the utility of microarrays and optical mapping in analysing outbreaks, reviews best practices and the limits of these technologies for pathogen differentiation, and it considers future integration with whole genome sequencing efforts.

  12. Existence of variant strains Fowlpox virus integrated with Reticuloendotheliosis virus in its genome in field isolates in Tanzania.

    Science.gov (United States)

    Mzula, Alexanda; Masola, Selemani N; Kasanga, Christopher J; Wambura, Philemon N

    2014-06-01

    Fowlpox virus (FPV) is one example of poultry viruses which undergoes recombination with Reticuloendotheliosis virus (REV). Trepidation had been raised, and it was well established on augmented pathogenicity of the FPV upon integration of the full intact REV. In this study, we therefore intended at assessing the integration of REV into FPV genome of the field isolates obtained in samples collected from different regions of Tanzania. DNA extraction of 85 samples (scabs) was performed, and FPV-specific PCR was done by the amplification of the highly conserved P4b gene. Evaluation of FPV-REV recombination was done to FPV-specific PCR positively identified samples by amplifying the env gene and REV long terminal repeats (5' LTR). A 578-bp PCR product was amplified from 43 samples. We are reporting for the first time in Tanzania the existence of variant stains of FPV integrated with REV in its genome as 65 % of FPV identified isolates were having full intact REV integration, 21 % had partial FPV-REV env gene integration and 5 % had partial 5' LTR integration. Despite of the fact that FPV-REV integrated stains prevailed, FPV-REV-free isolates (9 %) also existed. In view of the fact that full intact REV integration is connected with increased pathogenicity of FPV, its existence in the FPV genome of most field isolates could have played a role in increased endemic, sporadic and recurring outbreaks in selected areas in Tanzania.

  13. Reduced functional integration and segregation of distributed neural systems underlying social and emotional information processing in autism spectrum disorders.

    Science.gov (United States)

    Rudie, Jeffrey D; Shehzad, Zarrar; Hernandez, Leanna M; Colich, Natalie L; Bookheimer, Susan Y; Iacoboni, Marco; Dapretto, Mirella

    2012-05-01

    A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Here, we present findings showing that ASD is characterized by a pattern of reduced functional integration as well as reduced segregation of large-scale brain networks. Twenty-three children with ASD and 25 typically developing matched controls underwent functional magnetic resonance imaging while passively viewing emotional face expressions. We examined whole-brain functional connectivity of two brain structures previously implicated in emotional face processing in autism: the amygdala bilaterally and the right pars opercularis of the inferior frontal gyrus (rIFGpo). In the ASD group, we observed reduced functional integration (i.e., less long-range connectivity) between amygdala and secondary visual areas, as well as reduced segregation between amygdala and dorsolateral prefrontal cortex. For the rIFGpo seed, we observed reduced functional integration with parietal cortex and increased integration with right frontal cortex as well as right nucleus accumbens. Finally, we observed reduced segregation between rIFGpo and the ventromedial prefrontal cortex. We propose that a systems-level approach-whereby the integration and segregation of large-scale brain networks in ASD is examined in relation to typical development-may provide a more detailed characterization of the neural basis of ASD.

  14. A Comparison of the neural correlates that underlie rule-based and information-integration category learning.

    Science.gov (United States)

    Carpenter, Kathryn L; Wills, Andy J; Benattayallah, Abdelmalek; Milton, Fraser

    2016-10-01

    The influential competition between verbal and implicit systems (COVIS) model proposes that category learning is driven by two competing neural systems-an explicit, verbal, system, and a procedural-based, implicit, system. In the current fMRI study, participants learned either a conjunctive, rule-based (RB), category structure that is believed to engage the explicit system, or an information-integration category structure that is thought to preferentially recruit the implicit system. The RB and information-integration category structures were matched for participant error rate, the number of relevant stimulus dimensions, and category separation. Under these conditions, considerable overlap in brain activation, including the prefrontal cortex, basal ganglia, and the hippocampus, was found between the RB and information-integration category structures. Contrary to the predictions of COVIS, the medial temporal lobes and in particular the hippocampus, key regions for explicit memory, were found to be more active in the information-integration condition than in the RB condition. No regions were more activated in RB than information-integration category learning. The implications of these results for theories of category learning are discussed. Hum Brain Mapp 37:3557-3574, 2016. © 2016 Wiley Periodicals, Inc.

  15. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

    Directory of Open Access Journals (Sweden)

    Jan Tønnesen

    Full Text Available Intrastriatal grafts of stem cell-derived dopamine (DA neurons induce behavioral recovery in animal models of Parkinson's disease (PD, but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2 and halorhodopsin (NpHR, respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

  16. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

    Science.gov (United States)

    Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T; Andersson, Angelica; Lundberg, Cecilia; Deisseroth, Karl; Arenas, Ernest; Lindvall, Olle; Kokaia, Merab

    2011-03-04

    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

  17. A Facial Expression Classification System Integrating Canny, Principal Component Analysis and Artificial Neural Network

    CERN Document Server

    Thai, Le Hoang; Hai, Tran Son

    2011-01-01

    Facial Expression Classification is an interesting research problem in recent years. There are a lot of methods to solve this problem. In this research, we propose a novel approach using Canny, Principal Component Analysis (PCA) and Artificial Neural Network. Firstly, in preprocessing phase, we use Canny for local region detection of facial images. Then each of local region's features will be presented based on Principal Component Analysis (PCA). Finally, using Artificial Neural Network (ANN)applies for Facial Expression Classification. We apply our proposal method (Canny_PCA_ANN) for recognition of six basic facial expressions on JAFFE database consisting 213 images posed by 10 Japanese female models. The experimental result shows the feasibility of our proposal method.

  18. Autoregressive Integrated Adaptive Neural Networks Classifier for EEG-P300 Classification

    Directory of Open Access Journals (Sweden)

    Demi Soetraprawata

    2013-06-01

    Full Text Available Brain Computer Interface has a potency to be applied in mechatronics apparatus and vehicles in the future. Compared to the other techniques, EEG is the most preferred for BCI designs. In this paper, a new adaptive neural network classifier of different mental activities from EEG-based P300 signals is proposed. To overcome the over-training that is caused by noisy and non-stationary data, the EEG signals are filtered and extracted using autoregressive models before passed to the adaptive neural networks classifier. To test the improvement in the EEG classification performance with the proposed method, comparative experiments were conducted using Bayesian Linear Discriminant Analysis. The experiment results show that the all subjects achieve a classification accuracy of 100%.

  19. Model Integrating Fuzzy Argument with Neural Network Enhancing the Performance of Active Queue Management

    Directory of Open Access Journals (Sweden)

    Nguyen Kim Quoc

    2015-08-01

    Full Text Available The bottleneck control by active queue management mechanisms at network nodes is essential. In recent years, some researchers have used fuzzy argument to improve the active queue management mechanisms to enhance the network performance. However, the projects using the fuzzy controller depend heavily on professionals and their parameters cannot be updated according to changes in the network, so the effectiveness of this mechanism is not high. Therefore, we propose a model combining the fuzzy controller with neural network (FNN to overcome the limitations above. Results of the training of the neural networks will find the optimal parameters for the adaptive fuzzy controller well to changes of the network. This improves the operational efficiency of the active queue management mechanisms at network nodes.

  20. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Science.gov (United States)

    Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T Jake

    2014-05-01

    Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host

  1. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Directory of Open Access Journals (Sweden)

    Qisheng Li

    2014-05-01

    Full Text Available Recent functional genomics studies including genome-wide small interfering RNA (siRNA screens demonstrated that hepatitis C virus (HCV exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp, single-cycle infectious particles (HCVsc, subgenomic replicons, and HCV cell culture systems (HCVcc, we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE, a proviral factor, and N-Myc down regulated Gene 1 (NDRG1, an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study

  2. The cost of wobble translation in fungal mitochondrial genomes: integration of two traditional hypotheses

    Directory of Open Access Journals (Sweden)

    Xia Xuhua

    2008-07-01

    Full Text Available Abstract Background Fungal and animal mitochondrial genomes typically have one tRNA for each synonymous codon family. The codon-anticodon adaptation hypothesis predicts that the wobble nucleotide of a tRNA anticodon should evolve towards maximizing Watson-Crick base pairing with the most frequently used codon within each synonymous codon family, whereas the wobble versatility hypothesis argues that the nucleotide at the wobble site should be occupied by a nucleotide most versatile in wobble pairing, i.e., the tRNA wobble nucleotide should be G for NNY codon families, and U for NNR and NNN codon families (where Y stands for C or U, R for A or G and N for any nucleotide. Results We here integrate these two traditional hypotheses on tRNA anticodons into a unified model based on an analysis of the wobble costs associated with different wobble base pairs. This novel approach allows the relative cost of wobble pairing to be qualitatively evaluated. A comprehensive study of 36 fungal genomes suggests very different costs between two kinds of U:G wobble pairs, i.e., (1 between a G at the wobble site of a tRNA anticodon and a U at the third codon position (designated MU3:G and (2 between a U at the wobble site of a tRNA anticodon and a G at the third codon position (designated MG3:U. Conclusion In general, MU3:G is much smaller than MG3:U, suggesting no selection against U-ending codons in NNY codon families with a wobble G in the tRNA anticodon but strong selection against G-ending codons in NNR codon families with a wobble U at the tRNA anticodon. This finding resolves several puzzling observations in fungal genomics and corroborates previous studies showing that U3:G wobble is energetically more favorable than G3:U wobble.

  3. Systemic Approach for Health Risk Assessment of Ambient Air Concentrations of Benzene in Petrochemical Environments: Integration of Fuzzy Logic, Artificial Neural Network, and IRIS Toxicity Method

    OpenAIRE

    Vahid NOVIN; Givehchi, Saeed; HOVEIDI, Hassan

    2016-01-01

    Background: Reliable methods are crucial to cope with uncertainties in the risk analysis process. The aim of this study is to develop an integrated approach to assessing risks of benzene in the petrochemical plant that produces benzene. We offer an integrated system to contribute imprecise variables into the health risk calculation.Methods: The project was conducted in Asaluyeh, southern Iran during the years from 2013 to 2014. Integrated method includes fuzzy logic and artificial neural netw...

  4. An Integrative Model for the Neural Mechanism of Eye Movement Desensitization and Reprocessing (EMDR)

    OpenAIRE

    Coubard, Olivier A.

    2016-01-01

    Since the seminal report by Shapiro that bilateral stimulation induces cognitive and emotional changes, 26 years of basic and clinical research have examined the effects of Eye Movement Desensitization and Reprocessing (EMDR) in anxiety disorders, particularly in post-traumatic stress disorder (PTSD). The present article aims at better understanding EMDR neural mechanism. I first review procedural aspects of EMDR protocol and theoretical hypothesis about EMDR effects, and develop the reasons ...

  5. An integrative model for the neural mechanism of Eye Movement Desensitization and Reprocessing (EMDR)

    OpenAIRE

    Coubard, Olivier A.

    2016-01-01

    Since the seminal report by Shapiro that bilateral stimulation induces cognitive and emotional changes, twenty-six years of basic and clinical research have examined the effects of Eye Movement Desensitization and Reprocessing (EMDR) in anxiety disorders, particularly in Post-Traumatic Stress Disorder (PTSD). The present article aims at better understanding EMDR neural mechanism. I first review procedural aspects of EMDR protocol and theoretical hypothesis about EMDR effects, and develop the ...

  6. Pathways for Genome Integrity in G2 Phase of the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Claus Storgaard Sørensen

    2012-11-01

    Full Text Available The maintenance of genome integrity is important for normal cellular functions, organism development and the prevention of diseases, such as cancer. Cellular pathways respond immediately to DNA breaks leading to the initiation of a multi-facetted DNA damage response, which leads to DNA repair and cell cycle arrest. Cell cycle checkpoints provide the cell time to complete replication and repair the DNA damage before it can continue to the next cell cycle phase. The G2/M checkpoint plays an especially important role in ensuring the propagation of error-free copies of the genome to each daughter cell. Here, we review recent progress in our understanding of DNA repair and checkpoint pathways in late S and G2 phases. This review will first describe the current understanding of normal cell cycle progression through G2 phase to mitosis. It will also discuss the DNA damage response including cell cycle checkpoint control and DNA double-strand break repair. Finally, we discuss the emerging concept that DNA repair pathways play a major role in the G2/M checkpoint pathway thereby blocking cell division as long as DNA lesions are present.

  7. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  8. Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing.

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology.

  9. VaProS: a database-integration approach for protein/genome information retrieval

    KAUST Repository

    Gojobori, Takashi

    2016-12-24

    Life science research now heavily relies on all sorts of databases for genome sequences, transcription, protein three-dimensional (3D) structures, protein–protein interactions, phenotypes and so forth. The knowledge accumulated by all the omics research is so vast that a computer-aided search of data is now a prerequisite for starting a new study. In addition, a combinatory search throughout these databases has a chance to extract new ideas and new hypotheses that can be examined by wet-lab experiments. By virtually integrating the related databases on the Internet, we have built a new web application that facilitates life science researchers for retrieving experts’ knowledge stored in the databases and for building a new hypothesis of the research target. This web application, named VaProS, puts stress on the interconnection between the functional information of genome sequences and protein 3D structures, such as structural effect of the gene mutation. In this manuscript, we present the notion of VaProS, the databases and tools that can be accessed without any knowledge of database locations and data formats, and the power of search exemplified in quest of the molecular mechanisms of lysosomal storage disease. VaProS can be freely accessed at http://p4d-info.nig.ac.jp/vapros/.

  10. Human Ageing Genomic Resources: <