WorldWideScience

Sample records for integrative genomics approach

  1. VERSE: a novel approach to detect virus integration in host genomes through reference genome customization.

    Science.gov (United States)

    Wang, Qingguo; Jia, Peilin; Zhao, Zhongming

    2015-01-01

    Fueled by widespread applications of high-throughput next generation sequencing (NGS) technologies and urgent need to counter threats of pathogenic viruses, large-scale studies were conducted recently to investigate virus integration in host genomes (for example, human tumor genomes) that may cause carcinogenesis or other diseases. A limiting factor in these studies, however, is rapid virus evolution and resulting polymorphisms, which prevent reads from aligning readily to commonly used virus reference genomes, and, accordingly, make virus integration sites difficult to detect. Another confounding factor is host genomic instability as a result of virus insertions. To tackle these challenges and improve our capability to identify cryptic virus-host fusions, we present a new approach that detects Virus intEgration sites through iterative Reference SEquence customization (VERSE). To the best of our knowledge, VERSE is the first approach to improve detection through customizing reference genomes. Using 19 human tumors and cancer cell lines as test data, we demonstrated that VERSE substantially enhanced the sensitivity of virus integration site detection. VERSE is implemented in the open source package VirusFinder 2 that is available at http://bioinfo.mc.vanderbilt.edu/VirusFinder/.

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

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available 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.

  3. 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.

  4. Toward integration of genomic selection with crop modelling: the development of an integrated approach to predicting rice heading dates.

    Science.gov (United States)

    Onogi, Akio; Watanabe, Maya; Mochizuki, Toshihiro; Hayashi, Takeshi; Nakagawa, Hiroshi; Hasegawa, Toshihiro; Iwata, Hiroyoshi

    2016-04-01

    It is suggested that accuracy in predicting plant phenotypes can be improved by integrating genomic prediction with crop modelling in a single hierarchical model. Accurate prediction of phenotypes is important for plant breeding and management. Although genomic prediction/selection aims to predict phenotypes on the basis of whole-genome marker information, it is often difficult to predict phenotypes of complex traits in diverse environments, because plant phenotypes are often influenced by genotype-environment interaction. A possible remedy is to integrate genomic prediction with crop/ecophysiological modelling, which enables us to predict plant phenotypes using environmental and management information. To this end, in the present study, we developed a novel method for integrating genomic prediction with phenological modelling of Asian rice (Oryza sativa, L.), allowing the heading date of untested genotypes in untested environments to be predicted. The method simultaneously infers the phenological model parameters and whole-genome marker effects on the parameters in a Bayesian framework. By cultivating backcross inbred lines of Koshihikari × Kasalath in nine environments, we evaluated the potential of the proposed method in comparison with conventional genomic prediction, phenological modelling, and two-step methods that applied genomic prediction to phenological model parameters inferred from Nelder-Mead or Markov chain Monte Carlo algorithms. In predicting heading dates of untested lines in untested environments, the proposed and two-step methods tended to provide more accurate predictions than the conventional genomic prediction methods, particularly in environments where phenotypes from environments similar to the target environment were unavailable for training genomic prediction. The proposed method showed greater accuracy in prediction than the two-step methods in all cross-validation schemes tested, suggesting the potential of the integrated approach in

  5. 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.

  6. The European Renal Genome Project: An Integrated Approach Towards Understanding the Genetics of Kidney Development and Disease

    OpenAIRE

    Willnow, TE; Antignac, C; Brändli, AW; Christensen, EI; Cox, RD; Davidson, D; Davies, JA; Devuyst, O; Eichele, G; Hastie, ND; Verroust, PJ; Schedl, A; Meij, IC

    2005-01-01

    Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a thr...

  7. Integrative computational approach for genome-based study of microbial lipid-degrading enzymes.

    Science.gov (United States)

    Vorapreeda, Tayvich; Thammarongtham, Chinae; Laoteng, Kobkul

    2016-07-01

    Lipid-degrading or lipolytic enzymes have gained enormous attention in academic and industrial sectors. Several efforts are underway to discover new lipase enzymes from a variety of microorganisms with particular catalytic properties to be used for extensive applications. In addition, various tools and strategies have been implemented to unravel the functional relevance of the versatile lipid-degrading enzymes for special purposes. This review highlights the study of microbial lipid-degrading enzymes through an integrative computational approach. The identification of putative lipase genes from microbial genomes and metagenomic libraries using homology-based mining is discussed, with an emphasis on sequence analysis of conserved motifs and enzyme topology. Molecular modelling of three-dimensional structure on the basis of sequence similarity is shown to be a potential approach for exploring the structural and functional relationships of candidate lipase enzymes. The perspectives on a discriminative framework of cutting-edge tools and technologies, including bioinformatics, computational biology, functional genomics and functional proteomics, intended to facilitate rapid progress in understanding lipolysis mechanism and to discover novel lipid-degrading enzymes of microorganisms are discussed.

  8. 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 D...

  9. An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

    Science.gov (United States)

    Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

    2017-10-06

    Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

  10. A semantic web approach applied to integrative bioinformatics experimentation: a biological use case with genomics data.

    NARCIS (Netherlands)

    Post, L.J.G.; Roos, M.; Marshall, M.S.; van Driel, R.; Breit, T.M.

    2007-01-01

    The numerous public data resources make integrative bioinformatics experimentation increasingly important in life sciences research. However, it is severely hampered by the way the data and information are made available. The semantic web approach enhances data exchange and integration by providing

  11. New approaches to assessing the effects of mutagenic agents on the integrity of the human genome

    International Nuclear Information System (INIS)

    Elespuru, R.K.; Sankaranarayanan, K.

    2007-01-01

    Heritable genetic alterations, although individually rare, have a substantial collective health impact. Approximately 20% of these are new mutations of unknown cause. Assessment of the effect of exposures to DNA damaging agents, i.e. mutagenic chemicals and radiations, on the integrity of the human genome and on the occurrence of genetic disease remains a daunting challenge. Recent insights may explain why previous examination of human exposures to ionizing radiation, as in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New opportunities to assess the heritable genetic damaging effects of environmental mutagens are afforded by: (1) integration of knowledge on the molecular nature of genetic disorders and the molecular effects of mutagens; (2) the development of more practical assays for germline mutagenesis; (3) the likely use of population-based genetic screening in personalized medicine

  12. VaProS: a database-integration approach for protein/genome information retrieval

    KAUST Repository

    Gojobori, Takashi; Ikeo, Kazuho; Katayama, Yukie; Kawabata, Takeshi; Kinjo, Akira R.; Kinoshita, Kengo; Kwon, Yeondae; Migita, Ohsuke; Mizutani, Hisashi; Muraoka, Masafumi; Nagata, Koji; Omori, Satoshi; Sugawara, Hideaki; Yamada, Daichi; Yura, Kei

    2016-01-01

    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/.

  13. 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/.

  14. Statistical Methods in Integrative Genomics

    Science.gov (United States)

    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 future research directions. PMID:27482531

  15. Integrating genomics into evolutionary medicine.

    Science.gov (United States)

    Rodríguez, Juan Antonio; Marigorta, Urko M; Navarro, Arcadi

    2014-12-01

    The application of the principles of evolutionary biology into medicine was suggested long ago and is already providing insight into the ultimate causes of disease. However, a full systematic integration of medical genomics and evolutionary medicine is still missing. Here, we briefly review some cases where the combination of the two fields has proven profitable and highlight two of the main issues hindering the development of evolutionary genomic medicine as a mature field, namely the dissociation between fitness and health and the still considerable difficulties in predicting phenotypes from genotypes. We use publicly available data to illustrate both problems and conclude that new approaches are needed for evolutionary genomic medicine to overcome these obstacles. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. From Genome to Phenotype: An Integrative Approach to Evaluate the Biodiversity of Lactococcus lactis

    Science.gov (United States)

    Laroute, Valérie; Tormo, Hélène; Couderc, Christel; Mercier-Bonin, Muriel; Le Bourgeois, Pascal; Cocaign-Bousquet, Muriel; Daveran-Mingot, Marie-Line

    2017-01-01

    Lactococcus lactis is one of the most extensively used lactic acid bacteria for the manufacture of dairy products. Exploring the biodiversity of L. lactis is extremely promising both to acquire new knowledge and for food and health-driven applications. L. lactis is divided into four subspecies: lactis, cremoris, hordniae and tructae, but only subsp. lactis and subsp. cremoris are of industrial interest. Due to its various biotopes, Lactococcus subsp. lactis is considered the most diverse. The diversity of L. lactis subsp. lactis has been assessed at genetic, genomic and phenotypic levels. Multi-Locus Sequence Type (MLST) analysis of strains from different origins revealed that the subsp. lactis can be classified in two groups: “domesticated” strains with low genetic diversity, and “environmental” strains that are the main contributors of the genetic diversity of the subsp. lactis. As expected, the phenotype investigation of L. lactis strains reported here revealed highly diverse carbohydrate metabolism, especially in plant- and gut-derived carbohydrates, diacetyl production and stress survival. The integration of genotypic and phenotypic studies could improve the relevance of screening culture collections for the selection of strains dedicated to specific functions and applications. PMID:28534821

  17. Integrative genomic approaches to dissect clinically-significant relationships between the VDR cistrome and gene expression in primary colon cancer.

    Science.gov (United States)

    Long, Mark D; Campbell, Moray J

    2017-10-01

    Recently, we undertook a pan-cancer analyses of the nuclear hormone receptor (NR) superfamily in The Cancer Genome Atlas (TCGA), and revealed that the vitamin D receptor (NR1I1/VDR) was commonly and significantly down-regulated specifically in colon adenocarcinoma cohort (COAD). To examine the consequence of down-regulated VDR expression we re-analyzed VDR chromatin immunoprecipitation sequencing (ChIP-Seq) data from LS180 colon cancer cells (GSE31939). This analysis identified 1809 loci that displayed significant (p.adjcolon tumor suppressor, Galactin 4) had significantly shorted disease free survival. These analyses suggest that reduced expression of VDR in colon cancer (but neither loss nor mutation) changes the actions of the VDR by both dampening the expression of tumor suppressors (e.g. LGALS4) whilst either stabilizing or not down-regulating expression of oncogenes (e.g. Carbonic Anhydrase 9 (CA9)). These integrative genomic approaches are relatively generic and applicable to the study of any transcription factor. Copyright © 2016. Published by Elsevier Ltd.

  18. NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.

    Science.gov (United States)

    Chandrani, P; Kulkarni, V; Iyer, P; Upadhyay, P; Chaubal, R; Das, P; Mulherkar, R; Singh, R; Dutt, A

    2015-06-09

    Human papilloma virus (HPV) accounts for the most common cause of all virus-associated human cancers. Here, we describe the first graphic user interface (GUI)-based automated tool 'HPVDetector', for non-computational biologists, exclusively for detection and annotation of the HPV genome based on next-generation sequencing data sets. We developed a custom-made reference genome that comprises of human chromosomes along with annotated genome of 143 HPV types as pseudochromosomes. The tool runs on a dual mode as defined by the user: a 'quick mode' to identify presence of HPV types and an 'integration mode' to determine genomic location for the site of integration. The input data can be a paired-end whole-exome, whole-genome or whole-transcriptome data set. The HPVDetector is available in public domain for download: http://www.actrec.gov.in/pi-webpages/AmitDutt/HPVdetector/HPVDetector.html. On the basis of our evaluation of 116 whole-exome, 23 whole-transcriptome and 2 whole-genome data, we were able to identify presence of HPV in 20 exomes and 4 transcriptomes of cervical and head and neck cancer tumour samples. Using the inbuilt annotation module of HPVDetector, we found predominant integration of viral gene E7, a known oncogene, at known 17q21, 3q27, 7q35, Xq28 and novel sites of integration in the human genome. Furthermore, co-infection with high-risk HPVs such as 16 and 31 were found to be mutually exclusive compared with low-risk HPV71. HPVDetector is a simple yet precise and robust tool for detecting HPV from tumour samples using variety of next-generation sequencing platforms including whole genome, whole exome and transcriptome. Two different modes (quick detection and integration mode) along with a GUI widen the usability of HPVDetector for biologists and clinicians with minimal computational knowledge.

  19. SBH and the integration of complementary approaches in the mapping, sequencing, and understanding of complex genomes

    Energy Technology Data Exchange (ETDEWEB)

    Drmanac, R.; Drmanac, S.; Labat, I.; Vicentic, A.; Gemmell, A.; Stavropoulos, N.; Jarvis, J.

    1992-01-01

    A variant of sequencing by hybridization (SBH) is being developed with a potential to inexpensively determine up to 100 million base pairs per year. The method comprises (1) arraying short clones in 864-well plates; (2) growth of the M13 clones or PCR of the inserts; (3) automated spotting of DNAs by corresponding pin-arrays; (4) hybridization of dotted samples with 200-3000 [sup 32]P- or [sup 33]P-labeled 6- to 8-mer probes; and (5) scoring hybridization signals using storage phosphor plates. Some 200 7- to 8-mers can provide an inventory of the genes if CDNA clones are hybridized, or can define the order of 2-kb genomic clones, creating physical and structural maps with 100-bp resolution; the distribution of G+C, LINEs, SINEs, and gene families would be revealed. cDNAs that represent new genes and genomic clones in regions of interest selected by SBH can be sequenced by a gel method. Uniformly distributed clones from the previous step will be hybridized with 2000--3000 6- to 8-mers. As a result, approximately 50--60% of the genomic regions containing members of large repetitive and gene families and those families represented in GenBank would be completely sequenced. In the less redundant regions, every base pair is expected to be read with 3-4 probes, but the complete sequence can not be reconstructed. Such partial sequences allow the inference of similarity and the recognition of coding, regulatory, and repetitive sequences, as well as study of the evolutionary processes all the way up to the species delineation.

  20. SBH and the integration of complementary approaches in the mapping, sequencing, and understanding of complex genomes

    Energy Technology Data Exchange (ETDEWEB)

    Drmanac, R.; Drmanac, S.; Labat, I.; Vicentic, A.; Gemmell, A.; Stavropoulos, N.; Jarvis, J.

    1992-12-01

    A variant of sequencing by hybridization (SBH) is being developed with a potential to inexpensively determine up to 100 million base pairs per year. The method comprises (1) arraying short clones in 864-well plates; (2) growth of the M13 clones or PCR of the inserts; (3) automated spotting of DNAs by corresponding pin-arrays; (4) hybridization of dotted samples with 200-3000 {sup 32}P- or {sup 33}P-labeled 6- to 8-mer probes; and (5) scoring hybridization signals using storage phosphor plates. Some 200 7- to 8-mers can provide an inventory of the genes if CDNA clones are hybridized, or can define the order of 2-kb genomic clones, creating physical and structural maps with 100-bp resolution; the distribution of G+C, LINEs, SINEs, and gene families would be revealed. cDNAs that represent new genes and genomic clones in regions of interest selected by SBH can be sequenced by a gel method. Uniformly distributed clones from the previous step will be hybridized with 2000--3000 6- to 8-mers. As a result, approximately 50--60% of the genomic regions containing members of large repetitive and gene families and those families represented in GenBank would be completely sequenced. In the less redundant regions, every base pair is expected to be read with 3-4 probes, but the complete sequence can not be reconstructed. Such partial sequences allow the inference of similarity and the recognition of coding, regulatory, and repetitive sequences, as well as study of the evolutionary processes all the way up to the species delineation.

  1. SBH and the integration of complementary approaches in the mapping, sequencing, and understanding of complex genomes

    International Nuclear Information System (INIS)

    Drmanac, R.; Drmanac, S.; Labat, I.; Vicentic, A.; Gemmell, A.; Stavropoulos, N.; Jarvis, J.

    1992-01-01

    A variant of sequencing by hybridization (SBH) is being developed with a potential to inexpensively determine up to 100 million base pairs per year. The method comprises (1) arraying short clones in 864-well plates; (2) growth of the M13 clones or PCR of the inserts; (3) automated spotting of DNAs by corresponding pin-arrays; (4) hybridization of dotted samples with 200-3000 32 P- or 33 P-labeled 6- to 8-mer probes; and (5) scoring hybridization signals using storage phosphor plates. Some 200 7- to 8-mers can provide an inventory of the genes if CDNA clones are hybridized, or can define the order of 2-kb genomic clones, creating physical and structural maps with 100-bp resolution; the distribution of G+C, LINEs, SINEs, and gene families would be revealed. cDNAs that represent new genes and genomic clones in regions of interest selected by SBH can be sequenced by a gel method. Uniformly distributed clones from the previous step will be hybridized with 2000--3000 6- to 8-mers. As a result, approximately 50--60% of the genomic regions containing members of large repetitive and gene families and those families represented in GenBank would be completely sequenced. In the less redundant regions, every base pair is expected to be read with 3-4 probes, but the complete sequence can not be reconstructed. Such partial sequences allow the inference of similarity and the recognition of coding, regulatory, and repetitive sequences, as well as study of the evolutionary processes all the way up to the species delineation

  2. IGESS: a statistical approach to integrating individual-level genotype data and summary statistics in genome-wide association studies.

    Science.gov (United States)

    Dai, Mingwei; Ming, Jingsi; Cai, Mingxuan; Liu, Jin; Yang, Can; Wan, Xiang; Xu, Zongben

    2017-09-15

    Results from genome-wide association studies (GWAS) suggest that a complex phenotype is often affected by many variants with small effects, known as 'polygenicity'. Tens of thousands of samples are often required to ensure statistical power of identifying these variants with small effects. However, it is often the case that a research group can only get approval for the access to individual-level genotype data with a limited sample size (e.g. a few hundreds or thousands). Meanwhile, summary statistics generated using single-variant-based analysis are becoming publicly available. The sample sizes associated with the summary statistics datasets are usually quite large. How to make the most efficient use of existing abundant data resources largely remains an open question. In this study, we propose a statistical approach, IGESS, to increasing statistical power of identifying risk variants and improving accuracy of risk prediction by i ntegrating individual level ge notype data and s ummary s tatistics. An efficient algorithm based on variational inference is developed to handle the genome-wide analysis. Through comprehensive simulation studies, we demonstrated the advantages of IGESS over the methods which take either individual-level data or summary statistics data as input. We applied IGESS to perform integrative analysis of Crohns Disease from WTCCC and summary statistics from other studies. IGESS was able to significantly increase the statistical power of identifying risk variants and improve the risk prediction accuracy from 63.2% ( ±0.4% ) to 69.4% ( ±0.1% ) using about 240 000 variants. The IGESS software is available at https://github.com/daviddaigithub/IGESS . zbxu@xjtu.edu.cn or xwan@comp.hkbu.edu.hk or eeyang@hkbu.edu.hk. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Integrated Approaches for Genome-wide Interrogation of the Druggable Non-olfactory G Protein-coupled Receptor Superfamily.

    Science.gov (United States)

    Roth, Bryan L; Kroeze, Wesley K

    2015-08-07

    G-protein-coupled receptors (GPCRs) are frequent and fruitful targets for drug discovery and development, as well as being off-targets for the side effects of a variety of medications. Much of the druggable non-olfactory human GPCR-ome remains under-interrogated, and we present here various approaches that we and others have used to shine light into these previously dark corners of the human genome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

    NARCIS (Netherlands)

    Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt; Kahn, René S.; Cahn, Wiepke; Linszen, Don H.; de Haan, Lieuwe; van Os, Jim; Krabbendam, Lydia; Myin-Germeys, Inez; Wiersma, Durk; Bruggeman, Richard; Mors, O.; Børglum, A. D.; Mortensen, P. B.; Pedersen, C. B.; Demontis, D.; Grove, J.; Mattheisen, M.; Hougaard, D. M.

    2014-01-01

    In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional

  5. Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

    Science.gov (United States)

    Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

    2017-03-01

    In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Genome-wide search for miRNA-target interactions in Arabidopsis thaliana with an integrated approach

    Directory of Open Access Journals (Sweden)

    Ding Jiandong

    2012-06-01

    Full Text Available Abstract Background MiRNA are about 22nt long small noncoding RNAs that post transcriptionally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI is vital to understand their function. Currently, several integrated computational programs and databases are available for animal miRNAs, the mechanisms of which are significantly different from plant miRNAs. Methods Here we present an integrated MTI prediction and analysis toolkit (imiRTP for Arabidopsis thaliana. It features two important functions: (i combination of several effective plant miRNA target prediction methods provides a sufficiently large MTI candidate set, and (ii different filters allow for an efficient selection of potential targets. The modularity of imiRTP enables the prediction of high quality targets on genome-wide scale. Moreover, predicted MTIs can be presented in various ways, which allows for browsing through the putative target sites as well as conducting simple and advanced analyses. Results Results show that imiRTP could always find high quality candidates compared with single method by choosing appropriate filter and parameter. And we also reveal that a portion of plant miRNA could bind target genes out of coding region. Based on our results, imiRTP could facilitate the further study of Arabidopsis miRNAs in real use. All materials of imiRTP are freely available under a GNU license at (http://admis.fudan.edu.cn/projects/imiRTP.htm.

  7. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  8. 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.

  9. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  10. Genomics Portals: integrative web-platform for mining genomics data.

    Science.gov (United States)

    Shinde, Kaustubh; Phatak, Mukta; Johannes, Freudenberg M; Chen, Jing; Li, Qian; Vineet, Joshi K; Hu, Zhen; Ghosh, Krishnendu; Meller, Jaroslaw; Medvedovic, Mario

    2010-01-13

    A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis. The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.

  11. Genomics Portals: integrative web-platform for mining genomics data

    Directory of Open Access Journals (Sweden)

    Ghosh Krishnendu

    2010-01-01

    Full Text Available Abstract Background A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Results Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc, and the integration with an extensive knowledge base that can be used in such analysis. Conclusion The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.

  12. phiGENOME: an integrative navigation throughout bacteriophage genomes.

    Science.gov (United States)

    Stano, Matej; Klucar, Lubos

    2011-11-01

    phiGENOME is a web-based genome browser generating dynamic and interactive graphical representation of phage genomes stored in the phiSITE, database of gene regulation in bacteriophages. phiGENOME is an integral part of the phiSITE web portal (http://www.phisite.org/phigenome) and it was optimised for visualisation of phage genomes with the emphasis on the gene regulatory elements. phiGENOME consists of three components: (i) genome map viewer built using Adobe Flash technology, providing dynamic and interactive graphical display of phage genomes; (ii) sequence browser based on precisely formatted HTML tags, providing detailed exploration of genome features on the sequence level and (iii) regulation illustrator, based on Scalable Vector Graphics (SVG) and designed for graphical representation of gene regulations. Bringing 542 complete genome sequences accompanied with their rich annotations and references, makes phiGENOME a unique information resource in the field of phage genomics. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Transcription as a Threat to Genome Integrity.

    Science.gov (United States)

    Gaillard, Hélène; Aguilera, Andrés

    2016-06-02

    Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant.

  14. Integration a functional approach

    CERN Document Server

    Bichteler, Klaus

    1998-01-01

    This book covers Lebesgue integration and its generalizations from Daniell's point of view, modified by the use of seminorms. Integrating functions rather than measuring sets is posited as the main purpose of measure theory. From this point of view Lebesgue's integral can be had as a rather straightforward, even simplistic, extension of Riemann's integral; and its aims, definitions, and procedures can be motivated at an elementary level. The notion of measurability, for example, is suggested by Littlewood's observations rather than being conveyed authoritatively through definitions of (sigma)-algebras and good-cut-conditions, the latter of which are hard to justify and thus appear mysterious, even nettlesome, to the beginner. The approach taken provides the additional benefit of cutting the labor in half. The use of seminorms, ubiquitous in modern analysis, speeds things up even further. The book is intended for the reader who has some experience with proofs, a beginning graduate student for example. It might...

  15. Integrating genomics into undergraduate nursing education.

    Science.gov (United States)

    Daack-Hirsch, Sandra; Dieter, Carla; Quinn Griffin, Mary T

    2011-09-01

    To prepare the next generation of nurses, faculty are now faced with the challenge of incorporating genomics into curricula. Here we discuss how to meet this challenge. Steps to initiate curricular changes to include genomics are presented along with a discussion on creating a genomic curriculum thread versus a standalone course. Ideas for use of print material and technology on genomic topics are also presented. Information is based on review of the literature and curriculum change efforts by the authors. In recognition of advances in genomics, the nursing profession is increasing an emphasis on the integration of genomics into professional practice and educational standards. Incorporating genomics into nurses' practices begins with changes in our undergraduate curricula. Information given in didactic courses should be reinforced in clinical practica, and Internet-based tools such as WebQuest, Second Life, and wikis offer attractive, up-to-date platforms to deliver this now crucial content. To provide information that may assist faculty to prepare the next generation of nurses to practice using genomics. © 2011 Sigma Theta Tau International.

  16. High throughput platforms for structural genomics of integral membrane proteins.

    Science.gov (United States)

    Mancia, Filippo; Love, James

    2011-08-01

    Structural genomics approaches on integral membrane proteins have been postulated for over a decade, yet specific efforts are lagging years behind their soluble counterparts. Indeed, high throughput methodologies for production and characterization of prokaryotic integral membrane proteins are only now emerging, while large-scale efforts for eukaryotic ones are still in their infancy. Presented here is a review of recent literature on actively ongoing structural genomics of membrane protein initiatives, with a focus on those aimed at implementing interesting techniques aimed at increasing our rate of success for this class of macromolecules. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    KAUST Repository

    Alam, Intikhab; Antunes, André ; Kamau, Allan; Ba Alawi, Wail; Kalkatawi, Manal M.; 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.

  18. 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.

  19. GAPIT: genome association and prediction integrated tool.

    Science.gov (United States)

    Lipka, Alexander E; Tian, Feng; Wang, Qishan; Peiffer, Jason; Li, Meng; Bradbury, Peter J; Gore, Michael A; Buckler, Edward S; Zhang, Zhiwu

    2012-09-15

    Software programs that conduct genome-wide association studies and genomic prediction and selection need to use methodologies that maximize statistical power, provide high prediction accuracy and run in a computationally efficient manner. We developed an R package called Genome Association and Prediction Integrated Tool (GAPIT) that implements advanced statistical methods including the compressed mixed linear model (CMLM) and CMLM-based genomic prediction and selection. The GAPIT package can handle large datasets in excess of 10 000 individuals and 1 million single-nucleotide polymorphisms with minimal computational time, while providing user-friendly access and concise tables and graphs to interpret results. http://www.maizegenetics.net/GAPIT. zhiwu.zhang@cornell.edu Supplementary data are available at Bioinformatics online.

  20. Integrative Genome Comparison of Primary and Metastatic Melanomas

    Science.gov (United States)

    Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

    2010-01-01

    A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

  1. Genomics approaches in the understanding of Entamoeba ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... Here, we reviewed recent advances in the efforts to understand ... expression regulation in E. histolytica by using genomic approaches based on microarray technology ... tic abscesses that result in approximately 70,000 -.

  2. Genomic integrity and the ageing brain.

    Science.gov (United States)

    Chow, Hei-man; Herrup, Karl

    2015-11-01

    DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

  3. Genomic Approaches in Marine Biodiversity and Aquaculture

    Directory of Open Access Journals (Sweden)

    Jorge A Huete-Pérez

    2013-01-01

    Full Text Available Recent advances in genomic and post-genomic technologies have now established the new standard in medical and biotechnological research. The introduction of next-generation sequencing, NGS,has resulted in the generation of thousands of genomes from all domains of life, including the genomes of complex uncultured microbial communities revealed through metagenomics. Although the application of genomics to marine biodiversity remains poorly developed overall, some noteworthy progress has been made in recent years. The genomes of various model marine organisms have been published and a few more are underway. In addition, the recent large-scale analysis of marine microbes, along with transcriptomic and proteomic approaches to the study of teleost fishes, mollusks and crustaceans, to mention a few, has provided a better understanding of phenotypic variability and functional genomics. The past few years have also seen advances in applications relevant to marine aquaculture and fisheries. In this review we introduce several examples of recent discoveries and progress made towards engendering genomic resources aimed at enhancing our understanding of marine biodiversity and promoting the development of aquaculture. Finally, we discuss the need for auspicious science policies to address challenges confronting smaller nations in the appropriate oversight of this growing domain as they strive to guarantee food security and conservation of their natural resources.

  4. Integrative genomics approaches validate PpYUC11-like as candidate gene for the stony hard trait in peach (P. persica L. Batsch).

    Science.gov (United States)

    Cirilli, Marco; Giovannini, Daniela; Ciacciulli, Angelo; Chiozzotto, Remo; Gattolin, Stefano; Rossini, Laura; Liverani, Alessandro; Bassi, Daniele

    2018-05-18

    Texture is one of the most important fruit quality attributes. In peach, stony hard (SH) is a recessive monogenic trait (hd/hd) that confers exceptionally prolonged firm flesh to fully ripe fruit. Previous studies have shown that the SH mutation affects the fruit ability to synthesize appropriate amounts of indol-3-acetic acid (IAA), which orchestrates the ripening processes through the activation of system 2 ethylene pathway. Allelic variation in a TC microsatellite located within the first intron of PpYUC11-like (a YUCCA-like auxin-biosynthesis gene) has been recently proposed as the causal mutation of the SH phenotype. The simple genetic determinism of the SH trait has been clarified through genome-wide association and LD analyses in a diverse set of accessions, restricting the hd locus to an interval of about 1.8 Mbp in chromosome 6. The comparison of fruit transcriptome data from non-SH (melting flesh) and SH accessions provided an expression patterns overview of the annotated transcripts within the hd locus, confirming the absence of PpYUC11-like expression in SH fruits. To explore further possible associations between genomic variants at the hd locus and the SH phenotype, re-sequencing data of the SH accession 'D41-62' were compared with several SH and non-SH accessions with different genetic backgrounds. A further step of validation was provided through the evaluation of variant-trait association in two bi-parental F 2 populations issued from the SH accession 'D41-62' and a panel of advanced breeding selections, showing perfect co-segregation of the PpYUC11-like intron TC 20 allele and the SH phenotype. In this study, we provide a multi-level validation of the genetic control of the SH trait through the integration of genome-wide association mapping, transcriptome analysis and whole-genome resequencing data for SH and non-SH accessions, and marker-trait association in a panel of advanced breeding selections and segregating progenies. Collectively, our data

  5. Variant Review with the Integrative Genomics Viewer.

    Science.gov (United States)

    Robinson, James T; Thorvaldsdóttir, Helga; Wenger, Aaron M; Zehir, Ahmet; Mesirov, Jill P

    2017-11-01

    Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org Cancer Res; 77(21); e31-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Population Genomics of Infectious and Integrated Wolbachia pipientis Genomes in Drosophila ananassae

    Science.gov (United States)

    Choi, Jae Young; Bubnell, Jaclyn E.; Aquadro, Charles F.

    2015-01-01

    Coevolution between Drosophila and its endosymbiont Wolbachia pipientis has many intriguing aspects. For example, Drosophila ananassae hosts two forms of W. pipientis genomes: One being the infectious bacterial genome and the other integrated into the host nuclear genome. Here, we characterize the infectious and integrated genomes of W. pipientis infecting D. ananassae (wAna), by genome sequencing 15 strains of D. ananassae that have either the infectious or integrated wAna genomes. Results indicate evolutionarily stable maternal transmission for the infectious wAna genome suggesting a relatively long-term coevolution with its host. In contrast, the integrated wAna genome showed pseudogene-like characteristics accumulating many variants that are predicted to have deleterious effects if present in an infectious bacterial genome. Phylogenomic analysis of sequence variation together with genotyping by polymerase chain reaction of large structural variations indicated several wAna variants among the eight infectious wAna genomes. In contrast, only a single wAna variant was found among the seven integrated wAna genomes examined in lines from Africa, south Asia, and south Pacific islands suggesting that the integration occurred once from a single infectious wAna genome and then spread geographically. Further analysis revealed that for all D. ananassae we examined with the integrated wAna genomes, the majority of the integrated wAna genomic regions is represented in at least two copies suggesting a double integration or single integration followed by an integrated genome duplication. The possible evolutionary mechanism underlying the widespread geographical presence of the duplicate integration of the wAna genome is an intriguing question remaining to be answered. PMID:26254486

  7. Integrative Genomics Viewer (IGV) | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    The Integrative Genomics Viewer (IGV) is a high-performance visualization tool for interactive exploration of large, integrated genomic datasets. It supports a wide variety of data types, including array-based and next-generation sequence data, and genomic annotations.

  8. Microbial genome analysis: the COG approach.

    Science.gov (United States)

    Galperin, Michael Y; Kristensen, David M; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2017-09-14

    For the past 20 years, the Clusters of Orthologous Genes (COG) database had been a popular tool for microbial genome annotation and comparative genomics. Initially created for the purpose of evolutionary classification of protein families, the COG have been used, apart from straightforward functional annotation of sequenced genomes, for such tasks as (i) unification of genome annotation in groups of related organisms; (ii) identification of missing and/or undetected genes in complete microbial genomes; (iii) analysis of genomic neighborhoods, in many cases allowing prediction of novel functional systems; (iv) analysis of metabolic pathways and prediction of alternative forms of enzymes; (v) comparison of organisms by COG functional categories; and (vi) prioritization of targets for structural and functional characterization. Here we review the principles of the COG approach and discuss its key advantages and drawbacks in microbial genome analysis. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

  9. Patient-controlled encrypted genomic data: an approach to advance clinical genomics

    Directory of Open Access Journals (Sweden)

    Trakadis Yannis J

    2012-07-01

    Full Text Available Abstract Background The revolution in DNA sequencing technologies over the past decade has made it feasible to sequence an individual’s whole genome at a relatively low cost. The potential value of the information generated by genomic technologies for medicine and society is enormous. However, in order for exome sequencing, and eventually whole genome sequencing, to be implemented clinically, a number of major challenges need to be overcome. For instance, obtaining meaningful informed-consent, managing incidental findings and the great volume of data generated (including multiple findings with uncertain clinical significance, re-interpreting the genomic data and providing additional counselling to patients as genetic knowledge evolves are issues that need to be addressed. It appears that medical genetics is shifting from the present “phenotype-first” medical model to a “data-first” model which leads to multiple complexities. Discussion This manuscript discusses the different challenges associated with integrating genomic technologies into clinical practice and describes a “phenotype-first” approach, namely, “Individualized Mutation-weighed Phenotype Search”, and its benefits. The proposed approach allows for a more efficient prioritization of the genes to be tested in a clinical lab based on both the patient’s phenotype and his/her entire genomic data. It simplifies “informed-consent” for clinical use of genomic technologies and helps to protect the patient’s autonomy and privacy. Overall, this approach could potentially render widespread use of genomic technologies, in the immediate future, practical, ethical and clinically useful. Summary The “Individualized Mutation-weighed Phenotype Search” approach allows for an incremental integration of genomic technologies into clinical practice. It ensures that we do not over-medicalize genomic data but, rather, continue our current medical model which is based on serving

  10. Advances in Ecological Speciation: an integrative approach.

    Science.gov (United States)

    Faria, Rui; Renaut, Sebastien; Galindo, Juan; Pinho, Catarina; Melo-Ferreira, José; Melo, Martim; Jones, Felicity; Salzburger, Walter; Schluter, Dolph; Butlin, Roger

    2014-02-01

    The role of natural selection in promoting reproductive isolation has received substantial renewed interest within the last two decades. As a consequence, the study of ecological speciation has become an extremely productive research area in modern evolutionary biology. Recent innovations in sequencing technologies offer an unprecedented opportunity to study the mechanisms involved in ecological speciation. Genome scans provide significant insights but have some important limitations; efforts are needed to integrate them with other approaches to make full use of the sequencing data deluge. An international conference 'Advances in Ecological Speciation' organized by the University of Porto (Portugal) aimed to review current progress in ecological speciation. Using some of the examples presented at the conference, we highlight the benefits of integrating ecological and genomic data and discuss different mechanisms of parallel evolution. Finally, future avenues of research are suggested to advance our knowledge concerning the role of natural selection in the establishment of reproductive isolation during ecological speciation. © 2013 John Wiley & Sons Ltd.

  11. 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.

  12. On genome-wide association studies for family-based designs: an integrative analysis approach combining ascertained family samples with unselected controls.

    NARCIS (Netherlands)

    Lasky-Su, J.; Won, S.; Mick, E.; Anney, R.J.; Franke, B.; Neale, B.; Biederman, J.; Smalley, S.L.; Loo, S.K.; Todorov, A.A.; Faraone, S.V.; Weiss, S.T.; Lange, C.

    2010-01-01

    Large numbers of control individuals with genome-wide genotype data are now available through various databases. These controls are regularly used in case-control genome-wide association studies (GWAS) to increase the statistical power. Controls are often "unselected" for the disease of interest and

  13. 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

  14. IMG: the integrated microbial genomes database and comparative analysis system

    Science.gov (United States)

    Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Grechkin, Yuri; Ratner, Anna; Jacob, Biju; Huang, Jinghua; Williams, Peter; Huntemann, Marcel; Anderson, Iain; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2012-01-01

    The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life 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. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp). PMID:22194640

  15. Integration of Genomic, Biologic, and Chemical Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer

    Science.gov (United States)

    2016-09-01

    in this progress report: p53 triple-negative breast cancer subtypes gene expression somatic cell genetics CRISPR / Cas 3. ACCOMPLISHMENTS Major...report, we described the creation of an isogenic p53 mutant TNBC cell line panel using CRISPR / Cas -mediated genome editing8 and the resultant...LOF null state. To validate that mutant p53 is directly responsible for this altered transcription, we will use the same CRISPR -mediated genome

  16. Functional genomics approaches in parasitic helminths.

    Science.gov (United States)

    Hagen, J; Lee, E F; Fairlie, W D; Kalinna, B H

    2012-01-01

    As research on parasitic helminths is moving into the post-genomic era, an enormous effort is directed towards deciphering gene function and to achieve gene annotation. The sequences that are available in public databases undoubtedly hold information that can be utilized for new interventions and control but the exploitation of these resources has until recently remained difficult. Only now, with the emergence of methods to genetically manipulate and transform parasitic worms will it be possible to gain a comprehensive understanding of the molecular mechanisms involved in nutrition, metabolism, developmental switches/maturation and interaction with the host immune system. This review focuses on functional genomics approaches in parasitic helminths that are currently used, to highlight potential applications of these technologies in the areas of cell biology, systems biology and immunobiology of parasitic helminths. © 2011 Blackwell Publishing Ltd.

  17. Data integration to prioritize drugs using genomics and curated data.

    Science.gov (United States)

    Louhimo, Riku; Laakso, Marko; Belitskin, Denis; Klefström, Juha; Lehtonen, Rainer; Hautaniemi, Sampsa

    2016-01-01

    Genomic alterations affecting drug target proteins occur in several tumor types and are prime candidates for patient-specific tailored treatments. Increasingly, patients likely to benefit from targeted cancer therapy are selected based on molecular alterations. The selection of a precision therapy benefiting most patients is challenging but can be enhanced with integration of multiple types of molecular data. Data integration approaches for drug prioritization have successfully integrated diverse molecular data but do not take full advantage of existing data and literature. We have built a knowledge-base which connects data from public databases with molecular results from over 2200 tumors, signaling pathways and drug-target databases. Moreover, we have developed a data mining algorithm to effectively utilize this heterogeneous knowledge-base. Our algorithm is designed to facilitate retargeting of existing drugs by stratifying samples and prioritizing drug targets. We analyzed 797 primary tumors from The Cancer Genome Atlas breast and ovarian cancer cohorts using our framework. FGFR, CDK and HER2 inhibitors were prioritized in breast and ovarian data sets. Estrogen receptor positive breast tumors showed potential sensitivity to targeted inhibitors of FGFR due to activation of FGFR3. Our results suggest that computational sample stratification selects potentially sensitive samples for targeted therapies and can aid in precision medicine drug repositioning. Source code is available from http://csblcanges.fimm.fi/GOPredict/.

  18. 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.

  19. 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.

  20. Integrating cancer genomic data into electronic health records

    Directory of Open Access Journals (Sweden)

    Jeremy L. Warner

    2016-10-01

    Full Text Available Abstract The rise of genomically targeted therapies and immunotherapy has revolutionized the practice of oncology in the last 10–15 years. At the same time, new technologies and the electronic health record (EHR in particular have permeated the oncology clinic. Initially designed as billing and clinical documentation systems, EHR systems have not anticipated the complexity and variety of genomic information that needs to be reviewed, interpreted, and acted upon on a daily basis. Improved integration of cancer genomic data with EHR systems will help guide clinician decision making, support secondary uses, and ultimately improve patient care within oncology clinics. Some of the key factors relating to the challenge of integrating cancer genomic data into EHRs include: the bioinformatics pipelines that translate raw genomic data into meaningful, actionable results; the role of human curation in the interpretation of variant calls; and the need for consistent standards with regard to genomic and clinical data. Several emerging paradigms for integration are discussed in this review, including: non-standardized efforts between individual institutions and genomic testing laboratories; “middleware” products that portray genomic information, albeit outside of the clinical workflow; and application programming interfaces that have the potential to work within clinical workflow. The critical need for clinical-genomic knowledge bases, which can be independent or integrated into the aforementioned solutions, is also discussed.

  1. Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.

    Directory of Open Access Journals (Sweden)

    David Lindgren

    Full Text Available Similar to other malignancies, urothelial carcinoma (UC is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21, and BCL2L1 (20q11. We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development.

  2. 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.

  3. Building a genome database using an object-oriented approach.

    Science.gov (United States)

    Barbasiewicz, Anna; Liu, Lin; Lang, B Franz; Burger, Gertraud

    2002-01-01

    GOBASE is a relational database that integrates data associated with mitochondria and chloroplasts. The most important data in GOBASE, i. e., molecular sequences and taxonomic information, are obtained from the public sequence data repository at the National Center for Biotechnology Information (NCBI), and are validated by our experts. Maintaining a curated genomic database comes with a towering labor cost, due to the shear volume of available genomic sequences and the plethora of annotation errors and omissions in records retrieved from public repositories. Here we describe our approach to increase automation of the database population process, thereby reducing manual intervention. As a first step, we used Unified Modeling Language (UML) to construct a list of potential errors. Each case was evaluated independently, and an expert solution was devised, and represented as a diagram. Subsequently, the UML diagrams were used as templates for writing object-oriented automation programs in the Java programming language.

  4. 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.

  5. An Integrated Approach to Biology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 8. An Integrated Approach to Biology. Aniket Bhattacharya. General Article Volume 16 Issue 8 August 2011 pp 742-753. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/016/08/0742-0753 ...

  6. 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

  7. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jizhong [Univ. of Oklahoma, Norman, OK (United States); He, Zhili [Univ. of Oklahoma, Norman, OK (United States)

    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.

  8. Ares I Integrated Test Approach

    Science.gov (United States)

    Taylor, Jim

    2008-01-01

    This slide presentation reviews the testing approach that NASA is developing for the Ares I launch vehicle. NASA is planning a complete series of development, qualification and verification tests. These include: (1) Upper stage engine sea-level and altitude testing (2) First stage development and qualification motors (3) Upper stage structural and thermal development and qualification test articles (4) Main Propulsion Test Article (MPTA) (5) Upper stage green run testing (6) Integrated Vehicle Ground Vibration Testing (IVGVT) and (7) Aerodynamic characterization testing.

  9. INE: a rice genome database with an integrated map view.

    Science.gov (United States)

    Sakata, K; Antonio, B A; Mukai, Y; Nagasaki, H; Sakai, Y; Makino, K; Sasaki, T

    2000-01-01

    The Rice Genome Research Program (RGP) launched a large-scale rice genome sequencing in 1998 aimed at decoding all genetic information in rice. A new genome database called INE (INtegrated rice genome Explorer) has been developed in order to integrate all the genomic information that has been accumulated so far and to correlate these data with the genome sequence. A web interface based on Java applet provides a rapid viewing capability in the database. The first operational version of the database has been completed which includes a genetic map, a physical map using YAC (Yeast Artificial Chromosome) clones and PAC (P1-derived Artificial Chromosome) contigs. These maps are displayed graphically so that the positional relationships among the mapped markers on each chromosome can be easily resolved. INE incorporates the sequences and annotations of the PAC contig. A site on low quality information ensures that all submitted sequence data comply with the standard for accuracy. As a repository of rice genome sequence, INE will also serve as a common database of all sequence data obtained by collaborating members of the International Rice Genome Sequencing Project (IRGSP). The database can be accessed at http://www. dna.affrc.go.jp:82/giot/INE. html or its mirror site at http://www.staff.or.jp/giot/INE.html

  10. 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.

  11. 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 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.

  12. Order and correlations in genomic DNA sequences. The spectral approach

    International Nuclear Information System (INIS)

    Lobzin, Vasilii V; Chechetkin, Vladimir R

    2000-01-01

    The structural analysis of genomic DNA sequences is discussed in the framework of the spectral approach, which is sufficiently universal due to the reciprocal correspondence and mutual complementarity of Fourier transform length scales. The spectral characteristics of random sequences of the same nucleotide composition possess the property of self-averaging for relatively short sequences of length M≥100-300. Comparison with the characteristics of random sequences determines the statistical significance of the structural features observed. Apart from traditional applications to the search for hidden periodicities, spectral methods are also efficient in studying mutual correlations in DNA sequences. By combining spectra for structure factors and correlation functions, not only integral correlations can be estimated but also their origin identified. Using the structural spectral entropy approach, the regularity of a sequence can be quantitatively assessed. A brief introduction to the problem is also presented and other major methods of DNA sequence analysis described. (reviews of topical problems)

  13. Improving Microbial Genome Annotations in an Integrated Database Context

    Science.gov (United States)

    Chen, I-Min A.; Markowitz, Victor M.; Chu, Ken; Anderson, Iain; Mavromatis, Konstantinos; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2013-01-01

    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/. PMID:23424620

  14. 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/.

  15. 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.

  16. A Genomics Approach to Tumor Gemome Analysis

    National Research Council Canada - National Science Library

    Collins, Colin

    2002-01-01

    Genomes of solid tumors are often highly rearranged and these rearrangements promote cancer progression through disruption of genes mediating immortality, survival, metastasis, and resistance to therapy...

  17. Human Papillomavirus Genome Integration and Head and Neck Cancer.

    Science.gov (United States)

    Pinatti, L M; Walline, H M; Carey, T E

    2018-06-01

    We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

  18. Malaysia implements the integrated approach.

    Science.gov (United States)

    1977-01-01

    Malaysia has implemented an integrated approach in providing family planning services to eligible couples. In 1964 the government of Malaysia adopted a national family planning program, and implementation began in the urban areas and extended into the rural areas. Other agencies are involved in providing family planning services and information including the Federation of Family Planning Associations, the Ministry of Health, the National Family Planning Board, and the Federal Land Development Authority. The number of women practicing contraception has increased from 20,726 in 1967 to 533,646 by 1976. and other methods, 3.9%, respectively. There has been an increase in the percentage of acceptors between ages 15-29 from 56% in 1968 to 71.3% in 1975. The 2nd Malaysian national plan will use a multidisciplinary approach to the problem.

  19. Genomics approaches in the understanding of Entamoeba ...

    African Journals Online (AJOL)

    Entamoeba histolytica is the intestinal protozoan parasite responsible for amebic colitis and liver abscesses, which cause mortality in many developing countries. The sequencing of the parasite genome provides new insights into the cellular workings and genome evolution of this major human pathogen. Here, we reviewed ...

  20. An efficient approach to BAC based assembly of complex genomes.

    Science.gov (United States)

    Visendi, Paul; Berkman, Paul J; Hayashi, Satomi; Golicz, Agnieszka A; Bayer, Philipp E; Ruperao, Pradeep; Hurgobin, Bhavna; Montenegro, Juan; Chan, Chon-Kit Kenneth; Staňková, Helena; Batley, Jacqueline; Šimková, Hana; Doležel, Jaroslav; Edwards, David

    2016-01-01

    There has been an exponential growth in the number of genome sequencing projects since the introduction of next generation DNA sequencing technologies. Genome projects have increasingly involved assembly of whole genome data which produces inferior assemblies compared to traditional Sanger sequencing of genomic fragments cloned into bacterial artificial chromosomes (BACs). While whole genome shotgun sequencing using next generation sequencing (NGS) is relatively fast and inexpensive, this method is extremely challenging for highly complex genomes, where polyploidy or high repeat content confounds accurate assembly, or where a highly accurate 'gold' reference is required. Several attempts have been made to improve genome sequencing approaches by incorporating NGS methods, to variable success. We present the application of a novel BAC sequencing approach which combines indexed pools of BACs, Illumina paired read sequencing, a sequence assembler specifically designed for complex BAC assembly, and a custom bioinformatics pipeline. We demonstrate this method by sequencing and assembling BAC cloned fragments from bread wheat and sugarcane genomes. We demonstrate that our assembly approach is accurate, robust, cost effective and scalable, with applications for complete genome sequencing in large and complex genomes.

  1. 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

  2. Approaches for in silico finishing of microbial genome sequences

    Directory of Open Access Journals (Sweden)

    Frederico Schmitt Kremer

    Full Text Available Abstract The introduction of next-generation sequencing (NGS had a significant effect on the availability of genomic information, leading to an increase in the number of sequenced genomes from a large spectrum of organisms. Unfortunately, due to the limitations implied by the short-read sequencing platforms, most of these newly sequenced genomes remained as “drafts”, incomplete representations of the whole genetic content. The previous genome sequencing studies indicated that finishing a genome sequenced by NGS, even bacteria, may require additional sequencing to fill the gaps, making the entire process very expensive. As such, several in silico approaches have been developed to optimize the genome assemblies and facilitate the finishing process. The present review aims to explore some free (open source, in many cases tools that are available to facilitate genome finishing.

  3. Approaches for in silico finishing of microbial genome sequences.

    Science.gov (United States)

    Kremer, Frederico Schmitt; McBride, Alan John Alexander; Pinto, Luciano da Silva

    The introduction of next-generation sequencing (NGS) had a significant effect on the availability of genomic information, leading to an increase in the number of sequenced genomes from a large spectrum of organisms. Unfortunately, due to the limitations implied by the short-read sequencing platforms, most of these newly sequenced genomes remained as "drafts", incomplete representations of the whole genetic content. The previous genome sequencing studies indicated that finishing a genome sequenced by NGS, even bacteria, may require additional sequencing to fill the gaps, making the entire process very expensive. As such, several in silico approaches have been developed to optimize the genome assemblies and facilitate the finishing process. The present review aims to explore some free (open source, in many cases) tools that are available to facilitate genome finishing.

  4. Integrated genomics and molecular breeding approaches for ...

    Indian Academy of Sciences (India)

    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 ...

  5. Integrated approaches to perceptual learning.

    Science.gov (United States)

    Jacobs, Robert A

    2010-04-01

    New technologies and new ways of thinking have recently led to rapid expansions in the study of perceptual learning. We describe three themes shared by many of the nine articles included in this topic on Integrated Approaches to Perceptual Learning. First, perceptual learning cannot be studied on its own because it is closely linked to other aspects of cognition, such as attention, working memory, decision making, and conceptual knowledge. Second, perceptual learning is sensitive to both the stimulus properties of the environment in which an observer exists and to the properties of the tasks that the observer needs to perform. Moreover, the environmental and task properties can be characterized through their statistical regularities. Finally, the study of perceptual learning has important implications for society, including implications for science education and medical rehabilitation. Contributed articles relevant to each theme are summarized. Copyright © 2010 Cognitive Science Society, Inc.

  6. An Integrative Bioinformatics Framework for Genome-scale Multiple Level Network Reconstruction of Rice

    Directory of Open Access Journals (Sweden)

    Liu Lili

    2013-06-01

    Full Text Available Understanding how metabolic reactions translate the genome of an organism into its phenotype is a grand challenge in biology. Genome-wide association studies (GWAS statistically connect genotypes to phenotypes, without any recourse to known molecular interactions, whereas a molecular mechanistic description ties gene function to phenotype through gene regulatory networks (GRNs, protein-protein interactions (PPIs and molecular pathways. Integration of different regulatory information levels of an organism is expected to provide a good way for mapping genotypes to phenotypes. However, the lack of curated metabolic model of rice is blocking the exploration of genome-scale multi-level network reconstruction. Here, we have merged GRNs, PPIs and genome-scale metabolic networks (GSMNs approaches into a single framework for rice via omics’ regulatory information reconstruction and integration. Firstly, we reconstructed a genome-scale metabolic model, containing 4,462 function genes, 2,986 metabolites involved in 3,316 reactions, and compartmentalized into ten subcellular locations. Furthermore, 90,358 pairs of protein-protein interactions, 662,936 pairs of gene regulations and 1,763 microRNA-target interactions were integrated into the metabolic model. Eventually, a database was developped for systematically storing and retrieving the genome-scale multi-level network of rice. This provides a reference for understanding genotype-phenotype relationship of rice, and for analysis of its molecular regulatory network.

  7. The Genome-Scale Integrated Networks in Microorganisms

    Directory of Open Access Journals (Sweden)

    Tong Hao

    2018-02-01

    Full Text Available The genome-scale cellular network has become a necessary tool in the systematic analysis of microbes. In a cell, there are several layers (i.e., types of the molecular networks, for example, genome-scale metabolic network (GMN, transcriptional regulatory network (TRN, and signal transduction network (STN. It has been realized that the limitation and inaccuracy of the prediction exist just using only a single-layer network. Therefore, the integrated network constructed based on the networks of the three types attracts more interests. The function of a biological process in living cells is usually performed by the interaction of biological components. Therefore, it is necessary to integrate and analyze all the related components at the systems level for the comprehensively and correctly realizing the physiological function in living organisms. In this review, we discussed three representative genome-scale cellular networks: GMN, TRN, and STN, representing different levels (i.e., metabolism, gene regulation, and cellular signaling of a cell’s activities. Furthermore, we discussed the integration of the networks of the three types. With more understanding on the complexity of microbial cells, the development of integrated network has become an inevitable trend in analyzing genome-scale cellular networks of microorganisms.

  8. DOE systems approach and integration

    International Nuclear Information System (INIS)

    Logan, J.A.

    1987-01-01

    Six sites are now disposing of most of DOE's currently generated waste. These are: Hanford, Idaho National Engineering Laboratory, Los Alamos National Laboratory, the Nevada Test Site, Oak Ridge, and Savannah River. Within DOE, experience with disposal of solid LLW has been that arid site disposal facilities (first four) appear to have performed well, while humid site disposal facilities (last two) have experienced some waste migration. DOE's intent, of course, is to operate all its waste disposal facilities so that public health and safety are not adversely affected. To ensure that this continues to be the case, activities are underway to increase use of waste form stabilization and engineered barriers where appropriate. For the sake of overall economy, these measures are to be applied as and where needed, through use of the systems approach. In this paper the author discusses two topics: the system approach, which DOE has decided to use for resolving waste disposal problems in the management of DOE's low-level wastes; and DOE's intended integration of activities underway at the waste management systems throughout DOE facilities. 2 figures

  9. 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

  10. 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

  11. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.

    Science.gov (United States)

    Thorvaldsdóttir, Helga; Robinson, James T; Mesirov, Jill P

    2013-03-01

    Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today's sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv, under a GNU LGPL open-source license.

  12. Human papillomavirus genome integration in squamous carcinogenesis: what have next-generation sequencing studies taught us?

    Science.gov (United States)

    Groves, Ian J; Coleman, Nicholas

    2018-05-01

    Human papillomavirus (HPV) infection is associated with ∼5% of all human cancers, including a range of squamous cell carcinomas. Persistent infection by high-risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an important event in HPV-associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation, and further genomic instability. However, the mechanisms by which HRHPV integration occur and by which the subsequent gene expression changes take place are incompletely understood. The advent of next-generation sequencing (NGS) of both RNA and DNA has allowed powerful interrogation of the association of HRHPVs with human disease, including precise determination of the sites of integration and the genomic rearrangements at integration loci. In turn, these data have indicated that integration occurs through two main mechanisms: looping integration and direct insertion. Improved understanding of integration sites is allowing further investigation of the factors that provide a competitive advantage to some integrants during disease progression. Furthermore, advanced approaches to the generation of genome-wide samples have given novel insights into the three-dimensional interactions within the nucleus, which could act as another layer of epigenetic control of both virus and host transcription. It is hoped that further advances in NGS techniques and analysis will not only allow the examination of further unanswered questions regarding HPV infection, but also direct new approaches to treating HPV-associated human disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John

  13. Genome Editing: A New Approach to Human Therapeutics.

    Science.gov (United States)

    Porteus, Matthew

    2016-01-01

    The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

  14. Genomic approaches in aquaculture and fisheries

    DEFF Research Database (Denmark)

    Cancela, M. Leonor; Bargelloni, Luca; Boudry, Pierre

    2010-01-01

    . Improving state-of-the-art genomics research in various aquaculture systems, as well as its industrial applications, remains one of the major challenges in this area and should be the focus of well developed strategies to be implemented in the next generation of projects. This chapter will first provide...

  15. 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.

  16. Ensembl Genomes: an integrative resource for genome-scale data from non-vertebrate species.

    Science.gov (United States)

    Kersey, Paul J; Staines, Daniel M; Lawson, Daniel; Kulesha, Eugene; Derwent, Paul; Humphrey, Jay C; Hughes, Daniel S T; Keenan, Stephan; Kerhornou, Arnaud; Koscielny, Gautier; Langridge, Nicholas; McDowall, Mark D; Megy, Karine; Maheswari, Uma; Nuhn, Michael; Paulini, Michael; Pedro, Helder; Toneva, Iliana; Wilson, Derek; Yates, Andrew; Birney, Ewan

    2012-01-01

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrative resource for genome-scale data from non-vertebrate species. The project exploits and extends technology (for genome annotation, analysis and dissemination) developed in the context of the (vertebrate-focused) Ensembl project and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. Since its launch in 2009, Ensembl Genomes has undergone rapid expansion, with the goal of providing coverage of all major experimental organisms, and additionally including taxonomic reference points to provide the evolutionary context in which genes can be understood. Against the backdrop of a continuing increase in genome sequencing activities in all parts of the tree of life, we seek to work, wherever possible, with the communities actively generating and using data, and are participants in a growing range of collaborations involved in the annotation and analysis of genomes.

  17. Reduced representation approaches to interrogate genome diversity in large repetitive plant genomes.

    Science.gov (United States)

    Hirsch, Cory D; Evans, Joseph; Buell, C Robin; Hirsch, Candice N

    2014-07-01

    Technology and software improvements in the last decade now provide methodologies to access the genome sequence of not only a single accession, but also multiple accessions of plant species. This provides a means to interrogate species diversity at the genome level. Ample diversity among accessions in a collection of species can be found, including single-nucleotide polymorphisms, insertions and deletions, copy number variation and presence/absence variation. For species with small, non-repetitive rich genomes, re-sequencing of query accessions is robust, highly informative, and economically feasible. However, for species with moderate to large sized repetitive-rich genomes, technical and economic barriers prevent en masse genome re-sequencing of accessions. Multiple approaches to access a focused subset of loci in species with larger genomes have been developed, including reduced representation sequencing, exome capture and transcriptome sequencing. Collectively, these approaches have enabled interrogation of diversity on a genome scale for large plant genomes, including crop species important to worldwide food security. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. From integrated control to integrated farming, an experimental approach

    NARCIS (Netherlands)

    Vereijken, P.H.

    1989-01-01

    Integrated control or integrated pest management (IPM), as envisaged originally, is not being practised to any large extent in arable farming, notwithstanding considerable research efforts. The reasons for this are discussed. A more basic approach called integrated farming is suggested. Preliminary

  19. Integration of genomic information with biological networks using Cytoscape.

    Science.gov (United States)

    Bauer-Mehren, Anna

    2013-01-01

    Cytoscape is an open-source software for visualizing, analyzing, and modeling biological networks. This chapter explains how to use Cytoscape to analyze the functional effect of sequence variations in the context of biological networks such as protein-protein interaction networks and signaling pathways. The chapter is divided into five parts: (1) obtaining information about the functional effect of sequence variation in a Cytoscape readable format, (2) loading and displaying different types of biological networks in Cytoscape, (3) integrating the genomic information (SNPs and mutations) with the biological networks, and (4) analyzing the effect of the genomic perturbation onto the network structure using Cytoscape built-in functions. Finally, we briefly outline how the integrated data can help in building mathematical network models for analyzing the effect of the sequence variation onto the dynamics of the biological system. Each part is illustrated by step-by-step instructions on an example use case and visualized by many screenshots and figures.

  20. 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/.

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

    Science.gov (United States)

    Jung, Sook; Jesudurai, Christopher; Staton, Margaret; Du, Zhidian; Ficklin, Stephen; Cho, Ilhyung; Abbott, Albert; Tomkins, Jeffrey; Main, Dorrie

    2004-09-09

    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. 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. 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/.

  2. Evolving approaches to the ethical management of genomic data.

    Science.gov (United States)

    McEwen, Jean E; Boyer, Joy T; Sun, Kathie Y

    2013-06-01

    The ethical landscape in the field of genomics is rapidly shifting. Plummeting sequencing costs, along with ongoing advances in bioinformatics, now make it possible to generate an enormous volume of genomic data about vast numbers of people. The informational richness, complexity, and frequently uncertain meaning of these data, coupled with evolving norms surrounding the sharing of data and samples and persistent privacy concerns, have generated a range of approaches to the ethical management of genomic information. As calls increase for the expanded use of broad or even open consent, and as controversy grows about how best to handle incidental genomic findings, these approaches, informed by normative analysis and empirical data, will continue to evolve alongside the science. Published by Elsevier Ltd.

  3. 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.

  4. 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.

  5. Data integration approaches using ETL

    Directory of Open Access Journals (Sweden)

    Alexandra Maria Ioana FLOREA

    2016-01-01

    Full Text Available Traditional data warehouses and ETL tools have been slowly pushed to expand their limits as big data has become a more and more prominent actor on the analytics stage. This paper analyzes and compares the features of Pentaho Data Integration and Oracle Data Integrator, two of the main data integration platforms. Such tools are relevant in the context of the evolution of the analytics field, which is expanding from classical business intelligence activities to the use and analysis of big data.

  6. Protecting genomic integrity in somatic cells and embryonic stem cells

    International Nuclear Information System (INIS)

    Hong, Y.; Cervantes, R.B.; Tichy, E.; Tischfield, J.A.; Stambrook, P.J.

    2007-01-01

    Mutation frequencies at some loci in mammalian somatic cells in vivo approach 10 -4 . The majority of these events occur as a consequence of loss of heterozygosity (LOH) due to mitotic recombination. Such high levels of DNA damage in somatic cells, which can accumulate with age, will cause injury and, after a latency period, may lead to somatic disease and ultimately death. This high level of DNA damage is untenable for germ cells, and by extrapolation for embryonic stem (ES) cells, that must recreate the organism. ES cells cannot tolerate such a high frequency of damage since mutations will immediately impact the altered cell, and subsequently the entire organism. Most importantly, the mutations may be passed on to future generations. ES cells, therefore, must have robust mechanisms to protect the integrity of their genomes. We have examined two such mechanisms. Firstly, we have shown that mutation frequencies and frequencies of mitotic recombination in ES cells are about 100-fold lower than in adult somatic cells or in isogenic mouse embryonic fibroblasts (MEFs). A second complementary protective mechanism eliminates those ES cells that have acquired a mutational burden, thereby maintaining a pristine population. Consistent with this hypothesis, ES cells lack a G1 checkpoint, and the two known signaling pathways that mediate the checkpoint are compromised. The checkpoint kinase, Chk2, which participates in both pathways is sequestered at centrosomes in ES cells and does not phosphorylate its substrates (i.e. p53 and Cdc25A) that must be modified to produce a G1 arrest. Ectopic expression of Chk2 does not rescue the p53-mediated pathway, but does restore the pathway mediated by Cdc25A. Wild type ES cells exposed to ionizing radiation do not accumulate in G1 but do so in S-phase and in G2. ES cells that ectopically express Chk2 undergo cell cycle arrest in G1 as well as G2, and appear to be protected from apoptosis

  7. 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.

  8. 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

  9. A Ranking Approach to Genomic Selection.

    Science.gov (United States)

    Blondel, Mathieu; Onogi, Akio; Iwata, Hiroyoshi; Ueda, Naonori

    2015-01-01

    Genomic selection (GS) is a recent selective breeding method which uses predictive models based on whole-genome molecular markers. Until now, existing studies formulated GS as the problem of modeling an individual's breeding value for a particular trait of interest, i.e., as a regression problem. To assess predictive accuracy of the model, the Pearson correlation between observed and predicted trait values was used. In this paper, we propose to formulate GS as the problem of ranking individuals according to their breeding value. Our proposed framework allows us to employ machine learning methods for ranking which had previously not been considered in the GS literature. To assess ranking accuracy of a model, we introduce a new measure originating from the information retrieval literature called normalized discounted cumulative gain (NDCG). NDCG rewards more strongly models which assign a high rank to individuals with high breeding value. Therefore, NDCG reflects a prerequisite objective in selective breeding: accurate selection of individuals with high breeding value. We conducted a comparison of 10 existing regression methods and 3 new ranking methods on 6 datasets, consisting of 4 plant species and 25 traits. Our experimental results suggest that tree-based ensemble methods including McRank, Random Forests and Gradient Boosting Regression Trees achieve excellent ranking accuracy. RKHS regression and RankSVM also achieve good accuracy when used with an RBF kernel. Traditional regression methods such as Bayesian lasso, wBSR and BayesC were found less suitable for ranking. Pearson correlation was found to correlate poorly with NDCG. Our study suggests two important messages. First, ranking methods are a promising research direction in GS. Second, NDCG can be a useful evaluation measure for GS.

  10. Visualization of RNA structure models within the Integrative Genomics Viewer.

    Science.gov (United States)

    Busan, Steven; Weeks, Kevin M

    2017-07-01

    Analyses of the interrelationships between RNA structure and function are increasingly important components of genomic studies. The SHAPE-MaP strategy enables accurate RNA structure probing and realistic structure modeling of kilobase-length noncoding RNAs and mRNAs. Existing tools for visualizing RNA structure models are not suitable for efficient analysis of long, structurally heterogeneous RNAs. In addition, structure models are often advantageously interpreted in the context of other experimental data and gene annotation information, for which few tools currently exist. We have developed a module within the widely used and well supported open-source Integrative Genomics Viewer (IGV) that allows visualization of SHAPE and other chemical probing data, including raw reactivities, data-driven structural entropies, and data-constrained base-pair secondary structure models, in context with linear genomic data tracks. We illustrate the usefulness of visualizing RNA structure in the IGV by exploring structure models for a large viral RNA genome, comparing bacterial mRNA structure in cells with its structure under cell- and protein-free conditions, and comparing a noncoding RNA structure modeled using SHAPE data with a base-pairing model inferred through sequence covariation analysis. © 2017 Busan and Weeks; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  11. Structured Matrix Completion with Applications to Genomic Data Integration.

    Science.gov (United States)

    Cai, Tianxi; Cai, T Tony; Zhang, Anru

    2016-01-01

    Matrix completion has attracted significant recent attention in many fields including statistics, applied mathematics and electrical engineering. Current literature on matrix completion focuses primarily on independent sampling models under which the individual observed entries are sampled independently. Motivated by applications in genomic data integration, we propose a new framework of structured matrix completion (SMC) to treat structured missingness by design. Specifically, our proposed method aims at efficient matrix recovery when a subset of the rows and columns of an approximately low-rank matrix are observed. We provide theoretical justification for the proposed SMC method and derive lower bound for the estimation errors, which together establish the optimal rate of recovery over certain classes of approximately low-rank matrices. Simulation studies show that the method performs well in finite sample under a variety of configurations. The method is applied to integrate several ovarian cancer genomic studies with different extent of genomic measurements, which enables us to construct more accurate prediction rules for ovarian cancer survival.

  12. 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.

  13. Genome-Wide Approaches to Drosophila Heart Development

    Directory of Open Access Journals (Sweden)

    Manfred Frasch

    2016-05-01

    Full Text Available The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control Drosophila cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated Drosophila genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to Drosophila heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level.

  14. 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.

  15. Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

    Science.gov (United States)

    Taylor, Alison M; Shih, Juliann; Ha, Gavin; Gao, Galen F; Zhang, Xiaoyang; Berger, Ashton C; Schumacher, Steven E; Wang, Chen; Hu, Hai; Liu, Jianfang; Lazar, Alexander J; Cherniack, Andrew D; Beroukhim, Rameen; Meyerson, Matthew

    2018-04-09

    Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. STINGRAY: system for integrated genomic resources and analysis.

    Science.gov (United States)

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

    2014-03-07

    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. 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 interface that makes the system intuitive, facilitating the tasks of data analysis and annotation. STINGRAY showed to be an easy to use and complete system for analyzing sequencing data. While both Sanger and NGS platforms are supported, the system could be faster using Sanger data, since the large NGS datasets could potentially slow down the MySQL database usage. STINGRAY is available at http://stingray.biowebdb.org and the open source code at http://sourceforge.net/projects/stingray-biowebdb/.

  17. INTEGRATED EXPERIENCE APPROACH TO LEARNING.

    Science.gov (United States)

    POSTLETHWAIT, S.N.; AND OTHERS

    THE USE OF AUDIOTUTORIAL TECHNIQUES FOR TEACHING INTRODUCTORY COLLEGE BOTANY IS DESCRIBED. SPECIFIC PRACTICES USED AT PURDUE UNIVERSITY TO ILLUSTRATE DIFFERENT FACETS OF THE APPROACH ARE ANALYZED. INCLUDED ARE INDEPENDENT STUDY SESSIONS, SMALL ASSEMBLY SESSIONS, GENERAL ASSEMBLY SESSIONS, AND HOME STUDY SESSIONS. ILLUSTRATIONS AND SPECIFICATIONS…

  18. Integrative approaches to computational biomedicine

    Science.gov (United States)

    Coveney, Peter V.; Diaz-Zuccarini, Vanessa; Graf, Norbert; Hunter, Peter; Kohl, Peter; Tegner, Jesper; Viceconti, Marco

    2013-01-01

    The new discipline of computational biomedicine is concerned with the application of computer-based techniques and particularly modelling and simulation to human health. Since 2007, this discipline has been synonymous, in Europe, with the name given to the European Union's ambitious investment in integrating these techniques with the eventual aim of modelling the human body as a whole: the virtual physiological human. This programme and its successors are expected, over the next decades, to transform the study and practice of healthcare, moving it towards the priorities known as ‘4P's’: predictive, preventative, personalized and participatory medicine.

  19. Integrative medicine approach to chronic pain.

    Science.gov (United States)

    Teets, Raymond Y; Dahmer, Stephen; Scott, Emilie

    2010-06-01

    Chronic pain can be a frustrating condition for patient and clinician. The integrative medicine approach to pain can offer hope, adding safe complementary and alternative medical (CAM) therapies to mitigate pain and suffering. Such CAM therapies include nutrition, supplements and herbs, manual medicine, acupuncture, yoga, and mind-body approaches. The evidence is heterogeneous regarding these approaches, but some evidence suggests efficacy and confirms safety. The integrative medicine approach can be beneficial in a patient with chronic pain. Copyright 2010 Elsevier Inc. All rights reserved.

  20. 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

  1. Statistical inference an integrated approach

    CERN Document Server

    Migon, Helio S; Louzada, Francisco

    2014-01-01

    Introduction Information The concept of probability Assessing subjective probabilities An example Linear algebra and probability Notation Outline of the bookElements of Inference Common statistical modelsLikelihood-based functions Bayes theorem Exchangeability Sufficiency and exponential family Parameter elimination Prior Distribution Entirely subjective specification Specification through functional forms Conjugacy with the exponential family Non-informative priors Hierarchical priors Estimation Introduction to decision theoryBayesian point estimation Classical point estimation Empirical Bayes estimation Comparison of estimators Interval estimation Estimation in the Normal model Approximating Methods The general problem of inference Optimization techniquesAsymptotic theory Other analytical approximations Numerical integration methods Simulation methods Hypothesis Testing Introduction Classical hypothesis testingBayesian hypothesis testing Hypothesis testing and confidence intervalsAsymptotic tests Prediction...

  2. 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

    2017-07-03

    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). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Functional integral approach to classical statistical dynamics

    International Nuclear Information System (INIS)

    Jensen, R.V.

    1980-04-01

    A functional integral method is developed for the statistical solution of nonlinear stochastic differential equations which arise in classical dynamics. The functional integral approach provides a very natural and elegant derivation of the statistical dynamical equations that have been derived using the operator formalism of Martin, Siggia, and Rose

  4. 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

  5. Integrated Artificial Intelligence Approaches for Disease Diagnostics.

    Science.gov (United States)

    Vashistha, Rajat; Chhabra, Deepak; Shukla, Pratyoosh

    2018-06-01

    Mechanocomputational techniques in conjunction with artificial intelligence (AI) are revolutionizing the interpretations of the crucial information from the medical data and converting it into optimized and organized information for diagnostics. It is possible due to valuable perfection in artificial intelligence, computer aided diagnostics, virtual assistant, robotic surgery, augmented reality and genome editing (based on AI) technologies. Such techniques are serving as the products for diagnosing emerging microbial or non microbial diseases. This article represents a combinatory approach of using such approaches and providing therapeutic solutions towards utilizing these techniques in disease diagnostics.

  6. 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

  7. Toward an Integrated Psychological Approach - Phase II

    International Development Research Centre (IDRC) Digital Library (Canada)

    Trauma, Development and Peacebuilding : Toward an Integrated Psychological Approach - Phase II. Over the past decade, the peace, conflict and development community has begun to question the value of medicalized approaches such as post-traumatic stress disorder (PTSD) in dealing with aftermath of political violence ...

  8. Combining genomic and proteomic approaches for epigenetics research

    Science.gov (United States)

    Han, Yumiao; Garcia, Benjamin A

    2014-01-01

    Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence. In this review, current methods, both genomic and proteomic, associated with epigenetics research are discussed. Among them, chromatin immunoprecipitation (ChIP) followed by sequencing and other ChIP-based techniques are powerful techniques for genome-wide profiling of DNA-binding proteins, histone post-translational modifications or nucleosome positions. However, mass spectrometry-based proteomics is increasingly being used in functional biological studies and has proved to be an indispensable tool to characterize histone modifications, as well as DNA–protein and protein–protein interactions. With the development of genomic and proteomic approaches, combination of ChIP and mass spectrometry has the potential to expand our knowledge of epigenetics research to a higher level. PMID:23895656

  9. 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

  10. Genome Investigations of Vector Competence in Aedes aegypti to Inform Novel Arbovirus Disease Control Approaches

    Directory of Open Access Journals (Sweden)

    David W. Severson

    2016-10-01

    Full Text Available Dengue (DENV, yellow fever, chikungunya, and Zika virus transmission to humans by a mosquito host is confounded by both intrinsic and extrinsic variables. Besides virulence factors of the individual arboviruses, likelihood of virus transmission is subject to variability in the genome of the primary mosquito vector, Aedes aegypti. The “vectorial capacity” of A. aegypti varies depending upon its density, biting rate, and survival rate, as well as its intrinsic ability to acquire, host and transmit a given arbovirus. This intrinsic ability is known as “vector competence”. Based on whole transcriptome analysis, several genes and pathways have been predicated to have an association with a susceptible or refractory response in A. aegypti to DENV infection. However, the functional genomics of vector competence of A. aegypti is not well understood, primarily due to lack of integrative approaches in genomic or transcriptomic studies. In this review, we focus on the present status of genomics studies of DENV vector competence in A. aegypti as limited information is available relative to the other arboviruses. We propose future areas of research needed to facilitate the integration of vector and virus genomics and environmental factors to work towards better understanding of vector competence and vectorial capacity in natural conditions.

  11. 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). PMID:24165883

  12. 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).

  13. MinGenome: An In Silico Top-Down Approach for the Synthesis of Minimized Genomes.

    Science.gov (United States)

    Wang, Lin; Maranas, Costas D

    2018-02-16

    Genome minimized strains offer advantages as production chassis by reducing transcriptional cost, eliminating competing functions and limiting unwanted regulatory interactions. Existing approaches for identifying stretches of DNA to remove are largely ad hoc based on information on presumably dispensable regions through experimentally determined nonessential genes and comparative genomics. Here we introduce a versatile genome reduction algorithm MinGenome that implements a mixed-integer linear programming (MILP) algorithm to identify in size descending order all dispensable contiguous sequences without affecting the organism's growth or other desirable traits. Known essential genes or genes that cause significant fitness or performance loss can be flagged and their deletion can be prohibited. MinGenome also preserves needed transcription factors and promoter regions ensuring that retained genes will be properly transcribed while also avoiding the simultaneous deletion of synthetic lethal pairs. The potential benefit of removing even larger contiguous stretches of DNA if only one or two essential genes (to be reinserted elsewhere) are within the deleted sequence is explored. We applied the algorithm to design a minimized E. coli strain and found that we were able to recapitulate the long deletions identified in previous experimental studies and discover alternative combinations of deletions that have not yet been explored in vivo.

  14. 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.

  15. An Approach for Integrating Toxicogenomic Data in Risk Assessment: The Dibutyl Phthalate Case Study

    Science.gov (United States)

    An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and ...

  16. Curriculum Integration Using Enterprise Resource Planning: An Integrative Case Approach

    Science.gov (United States)

    Cannon, David M.; Klein, Helen A; Koste, Lori L.; Magal, Simha R.

    2004-01-01

    Efforts to achieve greater curriculum integration in schools of business have included team teaching, student group projects, multidisciplinary cases, and, more recently, the use of enterprise resource planning (ERP) systems. Although these approaches are beneficial, they tend to be implemented on an ad hoc basis rather than through curriculum…

  17. 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 and ...

  18. An approach for integrating toxicogenomic data in risk assessment: The dibutyl phthalate case study

    Energy Technology Data Exchange (ETDEWEB)

    Euling, Susan Y., E-mail: euling.susan@epa.gov [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Thompson, Chad M. [ToxStrategies, Inc., 23501 Cinco Ranch Blvd., Suite G265, Katy, TX 77494 (United States); Chiu, Weihsueh A. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Benson, Robert [U.S. Environmental Protection Agency, Region 8, Mail code 8P-W, 1595 Wynkoop Street, Denver, CO 80202 (United States)

    2013-09-15

    An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate (DBP) was selected for the case study exercise. The scoping phase of the dibutyl phthalate case study was conducted by considering the available DBP genomic data, taken together with the entire data set, for whether they could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose–response. A description of weighing the available dibutyl phthalate data set for utility in risk assessment provides an example for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions—Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics?—were selected to focus the case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various qualitative and/or quantitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on experience from the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment. - Highlights: • Performed DBP case study for integrating genomic data in risk assessment • Present approach for considering genomic data in chemical risk assessment • Present recommendations for use of genomic data in chemical risk assessment.

  19. Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

    Directory of Open Access Journals (Sweden)

    Zhongqi Ge

    2018-04-01

    Full Text Available Summary: Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. : Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development. Keywords: ubiquitin pathway, pan-cancer analysis, The Cancer Genome Atlas, tumor subtype, cancer prognosis, therapeutic targets, biomarker, FBXW7

  20. Graph-based sequence annotation using a data integration approach.

    Science.gov (United States)

    Pesch, Robert; Lysenko, Artem; Hindle, Matthew; Hassani-Pak, Keywan; Thiele, Ralf; Rawlings, Christopher; Köhler, Jacob; Taubert, Jan

    2008-08-25

    The automated annotation of data from high throughput sequencing and genomics experiments is a significant challenge for bioinformatics. Most current approaches rely on sequential pipelines of gene finding and gene function prediction methods that annotate a gene with information from different reference data sources. Each function prediction method contributes evidence supporting a functional assignment. Such approaches generally ignore the links between the information in the reference datasets. These links, however, are valuable for assessing the plausibility of a function assignment and can be used to evaluate the confidence in a prediction. We are working towards a novel annotation system that uses the network of information supporting the function assignment to enrich the annotation process for use by expert curators and predicting the function of previously unannotated genes. In this paper we describe our success in the first stages of this development. We present the data integration steps that are needed to create the core database of integrated reference databases (UniProt, PFAM, PDB, GO and the pathway database Ara-Cyc) which has been established in the ONDEX data integration system. We also present a comparison between different methods for integration of GO terms as part of the function assignment pipeline and discuss the consequences of this analysis for improving the accuracy of gene function annotation. The methods and algorithms presented in this publication are an integral part of the ONDEX system which is freely available from http://ondex.sf.net/.

  1. CANDU plant life management - An integrated approach

    International Nuclear Information System (INIS)

    Hopkins, J.R.

    1998-01-01

    An integrated approach to plant life management has been developed for CANDU reactors. Strategies, methods, and procedures have been developed for assessment of critical systems structures and components and for implementing a reliability centred maintenance program. A Technology Watch program is being implemented to eliminate 'surprises'. Specific work has been identified for 1998. AECL is working on the integrated program with CANDU owners and seeks participation from other CANDU owners

  2. BG7: A New Approach for Bacterial Genome Annotation Designed for Next Generation Sequencing Data

    Science.gov (United States)

    Pareja-Tobes, Pablo; Manrique, Marina; Pareja-Tobes, Eduardo; Pareja, Eduardo; Tobes, Raquel

    2012-01-01

    BG7 is a new system for de novo bacterial, archaeal and viral genome annotation based on a new approach specifically designed for annotating genomes sequenced with next generation sequencing technologies. The system is versatile and able to annotate genes even in the step of preliminary assembly of the genome. It is especially efficient detecting unexpected genes horizontally acquired from bacterial or archaeal distant genomes, phages, plasmids, and mobile elements. From the initial phases of the gene annotation process, BG7 exploits the massive availability of annotated protein sequences in databases. BG7 predicts ORFs and infers their function based on protein similarity with a wide set of reference proteins, integrating ORF prediction and functional annotation phases in just one step. BG7 is especially tolerant to sequencing errors in start and stop codons, to frameshifts, and to assembly or scaffolding errors. The system is also tolerant to the high level of gene fragmentation which is frequently found in not fully assembled genomes. BG7 current version – which is developed in Java, takes advantage of Amazon Web Services (AWS) cloud computing features, but it can also be run locally in any operating system. BG7 is a fast, automated and scalable system that can cope with the challenge of analyzing the huge amount of genomes that are being sequenced with NGS technologies. Its capabilities and efficiency were demonstrated in the 2011 EHEC Germany outbreak in which BG7 was used to get the first annotations right the next day after the first entero-hemorrhagic E. coli genome sequences were made publicly available. The suitability of BG7 for genome annotation has been proved for Illumina, 454, Ion Torrent, and PacBio sequencing technologies. Besides, thanks to its plasticity, our system could be very easily adapted to work with new technologies in the future. PMID:23185310

  3. BG7: a new approach for bacterial genome annotation designed for next generation sequencing data.

    Directory of Open Access Journals (Sweden)

    Pablo Pareja-Tobes

    Full Text Available BG7 is a new system for de novo bacterial, archaeal and viral genome annotation based on a new approach specifically designed for annotating genomes sequenced with next generation sequencing technologies. The system is versatile and able to annotate genes even in the step of preliminary assembly of the genome. It is especially efficient detecting unexpected genes horizontally acquired from bacterial or archaeal distant genomes, phages, plasmids, and mobile elements. From the initial phases of the gene annotation process, BG7 exploits the massive availability of annotated protein sequences in databases. BG7 predicts ORFs and infers their function based on protein similarity with a wide set of reference proteins, integrating ORF prediction and functional annotation phases in just one step. BG7 is especially tolerant to sequencing errors in start and stop codons, to frameshifts, and to assembly or scaffolding errors. The system is also tolerant to the high level of gene fragmentation which is frequently found in not fully assembled genomes. BG7 current version - which is developed in Java, takes advantage of Amazon Web Services (AWS cloud computing features, but it can also be run locally in any operating system. BG7 is a fast, automated and scalable system that can cope with the challenge of analyzing the huge amount of genomes that are being sequenced with NGS technologies. Its capabilities and efficiency were demonstrated in the 2011 EHEC Germany outbreak in which BG7 was used to get the first annotations right the next day after the first entero-hemorrhagic E. coli genome sequences were made publicly available. The suitability of BG7 for genome annotation has been proved for Illumina, 454, Ion Torrent, and PacBio sequencing technologies. Besides, thanks to its plasticity, our system could be very easily adapted to work with new technologies in the future.

  4. Convergent functional genomics in addiction research - a translational approach to study candidate genes and gene networks.

    Science.gov (United States)

    Spanagel, Rainer

    2013-01-01

    Convergent functional genomics (CFG) is a translational methodology that integrates in a Bayesian fashion multiple lines of evidence from studies in human and animal models to get a better understanding of the genetics of a disease or pathological behavior. Here the integration of data sets that derive from forward genetics in animals and genetic association studies including genome wide association studies (GWAS) in humans is described for addictive behavior. The aim of forward genetics in animals and association studies in humans is to identify mutations (e.g. SNPs) that produce a certain phenotype; i.e. "from phenotype to genotype". Most powerful in terms of forward genetics is combined quantitative trait loci (QTL) analysis and gene expression profiling in recombinant inbreed rodent lines or genetically selected animals for a specific phenotype, e.g. high vs. low drug consumption. By Bayesian scoring genomic information from forward genetics in animals is then combined with human GWAS data on a similar addiction-relevant phenotype. This integrative approach generates a robust candidate gene list that has to be functionally validated by means of reverse genetics in animals; i.e. "from genotype to phenotype". It is proposed that studying addiction relevant phenotypes and endophenotypes by this CFG approach will allow a better determination of the genetics of addictive behavior.

  5. 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

  6. Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

    Directory of Open Access Journals (Sweden)

    Claudia Bartoli

    2017-05-01

    Full Text Available The emergence and re-emergence of plant pathogenic microorganisms are processes that imply perturbations in both host and pathogen ecological niches. Global change is largely assumed to drive the emergence of new etiological agents by altering the equilibrium of the ecological habitats which in turn places hosts more in contact with pathogen reservoirs. In this context, the number of epidemics is expected to increase dramatically in the next coming decades both in wild and crop plants. Under these considerations, the identification of the genetic variants underlying natural variation of resistance is a pre-requisite to estimate the adaptive potential of wild plant populations and to develop new breeding resistant cultivars. On the other hand, the prediction of pathogen's genetic determinants underlying disease emergence can help to identify plant resistance alleles. In the genomic era, whole genome sequencing combined with the development of statistical methods led to the emergence of Genome Wide Association (GWA mapping, a powerful tool for detecting genomic regions associated with natural variation of disease resistance in both wild and cultivated plants. However, GWA mapping has been less employed for the detection of genetic variants associated with pathogenicity in microbes. Here, we reviewed GWA studies performed either in plants or in pathogenic microorganisms (bacteria, fungi and oomycetes. In addition, we highlighted the benefits and caveats of the emerging joint GWA mapping approach that allows for the simultaneous identification of genes interacting between genomes of both partners. Finally, based on co-evolutionary processes in wild populations, we highlighted a phenotyping-free joint GWA mapping approach as a promising tool for describing the molecular landscape underlying plant - microbe interactions.

  7. The transformative potential of an integrative approach to pregnancy.

    Science.gov (United States)

    Eidem, Haley R; McGary, Kriston L; Capra, John A; Abbot, Patrick; Rokas, Antonis

    2017-09-01

    Complex traits typically involve diverse biological pathways and are shaped by numerous genetic and environmental factors. Pregnancy-associated traits and pathologies are further complicated by extensive communication across multiple tissues in two individuals, interactions between two genomes-maternal and fetal-that obscure causal variants and lead to genetic conflict, and rapid evolution of pregnancy-associated traits across mammals and in the human lineage. Given the multi-faceted complexity of human pregnancy, integrative approaches that synthesize diverse data types and analyses harbor tremendous promise to identify the genetic architecture and environmental influences underlying pregnancy-associated traits and pathologies. We review current research that addresses the extreme complexities of traits and pathologies associated with human pregnancy. We find that successful efforts to address the many complexities of pregnancy-associated traits and pathologies often harness the power of many and diverse types of data, including genome-wide association studies, evolutionary analyses, multi-tissue transcriptomic profiles, and environmental conditions. We propose that understanding of pregnancy and its pathologies will be accelerated by computational platforms that provide easy access to integrated data and analyses. By simplifying the integration of diverse data, such platforms will provide a comprehensive synthesis that transcends many of the inherent challenges present in studies of pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Inferring genetic architecture of complex traits using Bayesian integrative analysis of genome and transcriptiome data

    DEFF Research Database (Denmark)

    Ehsani, Alireza; Sørensen, Peter; Pomp, Daniel

    2012-01-01

    Background To understand the genetic architecture of complex traits and bridge the genotype-phenotype gap, it is useful to study intermediate -omics data, e.g. the transcriptome. The present study introduces a method for simultaneous quantification of the contributions from single nucleotide......-modal distribution of genomic values collapses, when gene expressions are added to the model Conclusions With increased availability of various -omics data, integrative approaches are promising tools for understanding the genetic architecture of complex traits. Partitioning of explained variances at the chromosome...

  9. Prokaryote genome fluidity: toward a system approach of the mobilome.

    Science.gov (United States)

    Toussaint, Ariane; Chandler, Mick

    2012-01-01

    The importance of horizontal/lateral gene transfer (LGT) in shaping the genomes of prokaryotic organisms has been recognized in recent years as a result of analysis of the increasing number of available genome sequences. LGT is largely due to the transfer and recombination activities of mobile genetic elements (MGEs). Bacterial and archaeal genomes are mosaics of vertically and horizontally transmitted DNA segments. This generates reticulate relationships between members of the prokaryotic world that are better represented by networks than by "classical" phylogenetic trees. In this review we summarize the nature and activities of MGEs, and the problems that presently limit their analysis on a large scale. We propose routes to improve their annotation in the flow of genomic and metagenomic sequences that currently exist and those that become available. We describe network analysis of evolutionary relationships among some MGE categories and sketch out possible developments of this type of approach to get more insight into the role of the mobilome in bacterial adaptation and evolution.

  10. Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR

    DEFF Research Database (Denmark)

    Jakočiūnas, Tadas; Jensen, Emil D.; Jensen, Michael Krogh

    2018-01-01

    and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking......Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome...... engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. Cas...

  11. Integrated Approach to User Account Management

    Science.gov (United States)

    Kesselman, Glenn; Smith, William

    2007-01-01

    IT environments consist of both Windows and other platforms. Providing user account management for this model has become increasingly diffi cult. If Microsoft#s Active Directory could be enhanced to extend a W indows identity for authentication services for Unix, Linux, Java and Macintosh systems, then an integrated approach to user account manag ement could be realized.

  12. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

    Science.gov (United States)

    Gonçalves, Juliana; Moreira, Elsa; Sequeira, Inês J.; Rodrigues, António S.; Rueff, José; Brás, Aldina

    2016-01-01

    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. PMID:27294106

  13. Statistical inference an integrated Bayesianlikelihood approach

    CERN Document Server

    Aitkin, Murray

    2010-01-01

    Filling a gap in current Bayesian theory, Statistical Inference: An Integrated Bayesian/Likelihood Approach presents a unified Bayesian treatment of parameter inference and model comparisons that can be used with simple diffuse prior specifications. This novel approach provides new solutions to difficult model comparison problems and offers direct Bayesian counterparts of frequentist t-tests and other standard statistical methods for hypothesis testing.After an overview of the competing theories of statistical inference, the book introduces the Bayes/likelihood approach used throughout. It pre

  14. Graph-based sequence annotation using a data integration approach

    Directory of Open Access Journals (Sweden)

    Pesch Robert

    2008-06-01

    Full Text Available The automated annotation of data from high throughput sequencing and genomics experiments is a significant challenge for bioinformatics. Most current approaches rely on sequential pipelines of gene finding and gene function prediction methods that annotate a gene with information from different reference data sources. Each function prediction method contributes evidence supporting a functional assignment. Such approaches generally ignore the links between the information in the reference datasets. These links, however, are valuable for assessing the plausibility of a function assignment and can be used to evaluate the confidence in a prediction. We are working towards a novel annotation system that uses the network of information supporting the function assignment to enrich the annotation process for use by expert curators and predicting the function of previously unannotated genes. In this paper we describe our success in the first stages of this development. We present the data integration steps that are needed to create the core database of integrated reference databases (UniProt, PFAM, PDB, GO and the pathway database Ara- Cyc which has been established in the ONDEX data integration system. We also present a comparison between different methods for integration of GO terms as part of the function assignment pipeline and discuss the consequences of this analysis for improving the accuracy of gene function annotation.

  15. THE FEMINIST APPROACH TO PSYCHOTHERAPY INTEGRATION

    Directory of Open Access Journals (Sweden)

    Lorena Božac Deležan

    2011-12-01

    Full Text Available The goal of Integrative Psychotherapy is to establish full inner and external contact (Moursund & Erskine, 2004. The most important goal in feminist therapy is the transformation of an individual as well as the transformation of the society as a whole (Herlihy & Corey, 2004. In my work I attempt to integrate both: to help the client establish inner and external contact, but also help him/her to become aware and recognize inner messages connected with his/her gender and replace them with constructive beliefs of his/her own, as well as for him/her to learn, regardless of his/her gender, to trust his/her intuition and experience. In this article I present my approach to integration in psychotherapy and the way I use feminist principles in Integrative Psychotherapy.

  16. Adapting legume crops to climate change using genomic approaches.

    Science.gov (United States)

    Mousavi-Derazmahalleh, Mahsa; Bayer, Philipp E; Hane, James K; Babu, Valliyodan; Nguyen, Henry T; Nelson, Matthew N; Erskine, William; Varshney, Rajeev K; Papa, Roberto; Edwards, David

    2018-03-30

    Our agricultural system and hence food security is threatened by combination of events, such as increasing population, the impacts of climate change and the need to a more sustainable development. Evolutionary adaptation may help some species to overcome environmental changes through new selection pressures driven by climate change. However, success of evolutionary adaptation is dependent on various factors, one of which is the extent of genetic variation available within species. Genomic approaches provide an exceptional opportunity to identify genetic variation that can be employed in crop improvement programs. In this review, we illustrate some of the routinely used genomics-based methods as well as recent breakthroughs, which facilitate assessment of genetic variation and discovery of adaptive genes in legumes. While additional information is needed, the current utility of selection tools indicate a robust ability to utilize existing variation among legumes to address the challenges of climate uncertainty. This article is protected by copyright. All rights reserved.

  17. 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 .

  18. Performance improvement integration: a whole systems approach.

    Science.gov (United States)

    Page, C K

    1999-02-01

    Performance improvement integration in health care organizations is a challenge for health care leaders. Required for accreditation by the Joint Commission on Accreditation of Healthcare Organizations (Joint Commission), performance improvement (PI) can be designed as a sustainable model for performance to survive in a turbulent period. Central Baptist Hospital developed a model for PI that focused on strategy established by the leadership team, delineated responsibility through the organizational structure of shared governance, and accountability for outcomes evidenced through the organization's profitability. Such an approach integrated into the culture of the organization can produce positive financial margins, positive customer satisfaction, and commendations from the Joint Commission.

  19. Dual-In/Out strategy for genes integration into bacterial chromosome: a novel approach to step-by-step construction of plasmid-less marker-less recombinant E. coli strains with predesigned genome structure

    Directory of Open Access Journals (Sweden)

    Biryukova Irina V

    2008-08-01

    Full Text Available Abstract Background The development of modern producer strains with metabolically engineered pathways poses special problems that often require manipulating many genes and expressing them individually at different levels or under separate regulatory controls. The construction of plasmid-less marker-less strains has many advantages for the further practical exploitation of these bacteria in industry. Such producer strains are usually constructed by sequential chromosome modifications including deletions and integration of genetic material. For these purposes complex methods based on in vitro and in vivo recombination processes have been developed. Results Here, we describe the new scheme of insertion of the foreign DNA for step-by-step construction of plasmid-less marker-less recombinant E. coli strains with chromosome structure designed in advance. This strategy, entitled as Dual-In/Out, based on the initial Red-driven insertion of artificial φ80-attB sites into desired points of the chromosome followed by two site-specific recombination processes: first, the φ80 system is used for integration of the recombinant DNA based on selective marker-carrier conditionally-replicated plasmid with φ80-attP-site, and second, the λ system is used for excision of inserted vector part, including the plasmid ori-replication and the marker, flanked by λ-attL/R-sites. Conclusion The developed Dual-In/Out strategy is a rather straightforward, but convenient combination of previously developed recombination methods: phages site-specific and general Red/ET-mediated. This new approach allows us to detail the design of future recombinant marker-less strains, carrying, in particular, rather large artificial insertions that could be difficult to introduce by usually used PCR-based Recombineering procedure. The developed strategy is simple and could be particularly useful for construction of strains for the biotechnological industry.

  20. 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.

  1. Introduction to solid mechanics an integrated approach

    CERN Document Server

    Lubliner, Jacob

    2017-01-01

    This expanded second edition presents in one text the concepts and processes covered in statics and mechanics of materials curricula following a systematic, topically integrated approach. Building on the novel pedagogy of fusing concepts covered in traditional undergraduate courses in rigid-body statics and deformable body mechanics, rather than simply grafting them together, this new edition develops further the authors’ very original treatment of solid mechanics with additional figures, an elaboration on selected solved problems, and additional text as well as a new subsection on viscoelasticity in response to students’ feedback. Introduction to Solid Mechanics: An Integrated Approach, Second Edition, offers a holistic treatment of the depth and breadth of solid mechanics and the inter-relationships of its underlying concepts. Proceeding from first principles to applications, the book stands as a whole greater than the sum of its parts.  .

  2. Data integration for plant genomics--exemplars from the integration of Arabidopsis thaliana databases.

    Science.gov (United States)

    Lysenko, Artem; Lysenko, Atem; Hindle, Matthew Morritt; Taubert, Jan; Saqi, Mansoor; Rawlings, Christopher John

    2009-11-01

    The development of a systems based approach to problems in plant sciences requires integration of existing information resources. However, the available information is currently often incomplete and dispersed across many sources and the syntactic and semantic heterogeneity of the data is a challenge for integration. In this article, we discuss strategies for data integration and we use a graph based integration method (Ondex) to illustrate some of these challenges with reference to two example problems concerning integration of (i) metabolic pathway and (ii) protein interaction data for Arabidopsis thaliana. We quantify the degree of overlap for three commonly used pathway and protein interaction information sources. For pathways, we find that the AraCyc database contains the widest coverage of enzyme reactions and for protein interactions we find that the IntAct database provides the largest unique contribution to the integrated dataset. For both examples, however, we observe a relatively small amount of data common to all three sources. Analysis and visual exploration of the integrated networks was used to identify a number of practical issues relating to the interpretation of these datasets. We demonstrate the utility of these approaches to the analysis of groups of coexpressed genes from an individual microarray experiment, in the context of pathway information and for the combination of coexpression data with an integrated protein interaction network.

  3. Brassica database (BRAD) version 2.0: integrating and mining Brassicaceae species genomic resources.

    Science.gov (United States)

    Wang, Xiaobo; Wu, Jian; Liang, Jianli; Cheng, Feng; Wang, Xiaowu

    2015-01-01

    The Brassica database (BRAD) was built initially to assist users apply Brassica rapa and Arabidopsis thaliana genomic data efficiently to their research. However, many Brassicaceae genomes have been sequenced and released after its construction. These genomes are rich resources for comparative genomics, gene annotation and functional evolutionary studies of Brassica crops. Therefore, we have updated BRAD to version 2.0 (V2.0). In BRAD V2.0, 11 more Brassicaceae genomes have been integrated into the database, namely those of Arabidopsis lyrata, Aethionema arabicum, Brassica oleracea, Brassica napus, Camelina sativa, Capsella rubella, Leavenworthia alabamica, Sisymbrium irio and three extremophiles Schrenkiella parvula, Thellungiella halophila and Thellungiella salsuginea. BRAD V2.0 provides plots of syntenic genomic fragments between pairs of Brassicaceae species, from the level of chromosomes to genomic blocks. The Generic Synteny Browser (GBrowse_syn), a module of the Genome Browser (GBrowse), is used to show syntenic relationships between multiple genomes. Search functions for retrieving syntenic and non-syntenic orthologs, as well as their annotation and sequences are also provided. Furthermore, genome and annotation information have been imported into GBrowse so that all functional elements can be visualized in one frame. We plan to continually update BRAD by integrating more Brassicaceae genomes into the database. Database URL: http://brassicadb.org/brad/. © The Author(s) 2015. Published by Oxford University Press.

  4. Addressing uncertainties in the ERICA Integrated Approach

    International Nuclear Information System (INIS)

    Oughton, D.H.; Agueero, A.; Avila, R.; Brown, J.E.; Copplestone, D.; Gilek, M.

    2008-01-01

    Like any complex environmental problem, ecological risk assessment of the impacts of ionising radiation is confounded by uncertainty. At all stages, from problem formulation through to risk characterisation, the assessment is dependent on models, scenarios, assumptions and extrapolations. These include technical uncertainties related to the data used, conceptual uncertainties associated with models and scenarios, as well as social uncertainties such as economic impacts, the interpretation of legislation, and the acceptability of the assessment results to stakeholders. The ERICA Integrated Approach has been developed to allow an assessment of the risks of ionising radiation, and includes a number of methods that are intended to make the uncertainties and assumptions inherent in the assessment more transparent to users and stakeholders. Throughout its development, ERICA has recommended that assessors deal openly with the deeper dimensions of uncertainty and acknowledge that uncertainty is intrinsic to complex systems. Since the tool is based on a tiered approach, the approaches to dealing with uncertainty vary between the tiers, ranging from a simple, but highly conservative screening to a full probabilistic risk assessment including sensitivity analysis. This paper gives on overview of types of uncertainty that are manifest in ecological risk assessment and the ERICA Integrated Approach to dealing with some of these uncertainties

  5. 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.

  6. Cancer prevention, the need to preserve the integrity of the genome at all cost.

    Science.gov (United States)

    Okafor, M T; Nwagha, T U; Anusiem, C; Okoli, U A; Nubila, N I; Al-Alloosh, F; Udenyia, I J

    2018-05-01

    The entire genetic information carried by an organism makes up its genome. Genes have a diverse number of functions. They code different proteins for normal proliferation of cells. However, changes in the base sequence of genes affect their protein by-products which act as messengers for normal cellular functions such as proliferation and repairs. Salient processes for maintaining the integrity of the genome are hinged on intricate mechanisms put in place for the evolution to tackle genomic stresses. To discuss how cells sense and repair damage to their deoxyribonucleic acid (DNA) as well as to highlight how defects in the genes involved in DNA repair contribute to cancer development. Methodology: Online searches on the following databases such as Google Scholar, PubMed, Biomed Central, and SciELO were done. Attempt was made to review articles with keywords such as cancer, cell cycle, tumor suppressor genes, and DNA repair. The cell cycle, tumor suppression genes, DNA repair mechanism, as well as their contribution to cancer development, were discussed and reviewed. Knowledge on how cells detect and repair DNA damage through an array of mechanisms should allay our anxiety as regards cancer development. More studies on DNA damage detection and repair processes are important toward a holistic approach to cancer treatment.

  7. Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR.

    Science.gov (United States)

    Jakočiūnas, Tadas; Jensen, Emil D; Jensen, Michael K; Keasling, Jay D

    2018-01-01

    Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. CasEMBLR capitalizes on the CRISPR/Cas9 technology to generate double-strand breaks in genomic loci, thus prompting native homologous recombination (HR) machinery to integrate exogenously derived homology templates. As proof-of-principle for microbial cell factory development, CasEMBLR was used for one-step assembly and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking out two genes. This new method complements and improves the field of genome engineering in S. cerevisiae by providing a more flexible platform for rapid and precise strain building.

  8. 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.

  9. Community standards for genomic resources, genetic conservation, and data integration

    Science.gov (United States)

    Jill Wegrzyn; Meg Staton; Emily Grau; Richard Cronn; C. Dana Nelson

    2017-01-01

    Genetics and genomics are increasingly important in forestry management and conservation. Next generation sequencing can increase analytical power, but still relies on building on the structure of previously acquired data. Data standards and data sharing allow the community to maximize the analytical power of high throughput genomics data. The landscape of incomplete...

  10. GIGGLE: a search engine for large-scale integrated genome analysis

    Science.gov (United States)

    Layer, Ryan M; Pedersen, Brent S; DiSera, Tonya; Marth, Gabor T; Gertz, Jason; Quinlan, Aaron R

    2018-01-01

    GIGGLE is a genomics search engine that identifies and ranks the significance of genomic loci shared between query features and thousands of genome interval files. GIGGLE (https://github.com/ryanlayer/giggle) scales to billions of intervals and is over three orders of magnitude faster than existing methods. Its speed extends the accessibility and utility of resources such as ENCODE, Roadmap Epigenomics, and GTEx by facilitating data integration and hypothesis generation. PMID:29309061

  11. GIGGLE: a search engine for large-scale integrated genome analysis.

    Science.gov (United States)

    Layer, Ryan M; Pedersen, Brent S; DiSera, Tonya; Marth, Gabor T; Gertz, Jason; Quinlan, Aaron R

    2018-02-01

    GIGGLE is a genomics search engine that identifies and ranks the significance of genomic loci shared between query features and thousands of genome interval files. GIGGLE (https://github.com/ryanlayer/giggle) scales to billions of intervals and is over three orders of magnitude faster than existing methods. Its speed extends the accessibility and utility of resources such as ENCODE, Roadmap Epigenomics, and GTEx by facilitating data integration and hypothesis generation.

  12. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

    Science.gov (United States)

    Brat, Daniel J; Verhaak, Roel G W; Aldape, Kenneth D; Yung, W K Alfred; Salama, Sofie R; Cooper, Lee A D; Rheinbay, Esther; Miller, C Ryan; Vitucci, Mark; Morozova, Olena; Robertson, A Gordon; Noushmehr, Houtan; Laird, Peter W; Cherniack, Andrew D; Akbani, Rehan; Huse, Jason T; Ciriello, Giovanni; Poisson, Laila M; Barnholtz-Sloan, Jill S; Berger, Mitchel S; Brennan, Cameron; Colen, Rivka R; Colman, Howard; Flanders, Adam E; Giannini, Caterina; Grifford, Mia; Iavarone, Antonio; Jain, Rajan; Joseph, Isaac; Kim, Jaegil; Kasaian, Katayoon; Mikkelsen, Tom; Murray, Bradley A; O'Neill, Brian Patrick; Pachter, Lior; Parsons, Donald W; Sougnez, Carrie; Sulman, Erik P; Vandenberg, Scott R; Van Meir, Erwin G; von Deimling, Andreas; Zhang, Hailei; Crain, Daniel; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron; Bowen, Jay; Dicostanzo, Katie; Gastier-Foster, Julie; Leraas, Kristen M; Lichtenberg, Tara M; Pierson, Christopher R; Ramirez, Nilsa C; Taylor, Cynthia; Weaver, Stephanie; Wise, Lisa; Zmuda, Erik; Davidsen, Tanja; Demchok, John A; Eley, Greg; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Ozenberger, Bradley A; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Jensen, Mark A; Liu, Jia; Pihl, Todd; Raman, Rohini; Wan, Yunhu; Wu, Ye; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B; Beroukhim, Rameen; Bootwalla, Moiz S; Bowlby, Reanne; Bristow, Christopher A; Brooks, Denise; Butterfield, Yaron; Carlsen, Rebecca; Carter, Scott; Chin, Lynda; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Clarke, Amanda; Coetzee, Simon G; Dhalla, Noreen; Fennell, Tim; Fisher, Sheila; Gabriel, Stacey; Getz, Gad; Gibbs, Richard; Guin, Ranabir; Hadjipanayis, Angela; Hayes, D Neil; Hinoue, Toshinori; Hoadley, Katherine; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven; Jones, Corbin D; Kucherlapati, Raju; Lai, Phillip H; Lander, Eric; Lee, Semin; Lichtenstein, Lee; Ma, Yussanne; Maglinte, Dennis T; Mahadeshwar, Harshad S; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew L; Mieczkowski, Piotr A; Moore, Richard A; Mose, Lisle E; Mungall, Andrew J; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J; Parker, Joel S; Perou, Charles M; Protopopov, Alexei; Ren, Xiaojia; Roach, Jeffrey; Sabedot, Thaís S; Schein, Jacqueline; Schumacher, Steven E; Seidman, Jonathan G; Seth, Sahil; Shen, Hui; Simons, Janae V; Sipahimalani, Payal; Soloway, Matthew G; Song, Xingzhi; Sun, Huandong; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Thiessen, Nina; Triche, Timothy; Van Den Berg, David J; Veluvolu, Umadevi; Waring, Scot; Weisenberger, Daniel J; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Xu, Andrew W; Yang, Lixing; Zack, Travis I; Zhang, Jianhua; Aksoy, B Arman; Arachchi, Harindra; Benz, Chris; Bernard, Brady; Carlin, Daniel; Cho, Juok; DiCara, Daniel; Frazer, Scott; Fuller, Gregory N; Gao, JianJiong; Gehlenborg, Nils; Haussler, David; Heiman, David I; Iype, Lisa; Jacobsen, Anders; Ju, Zhenlin; Katzman, Sol; Kim, Hoon; Knijnenburg, Theo; Kreisberg, Richard Bailey; Lawrence, Michael S; Lee, William; Leinonen, Kalle; Lin, Pei; Ling, Shiyun; Liu, Wenbin; Liu, Yingchun; Liu, Yuexin; Lu, Yiling; Mills, Gordon; Ng, Sam; Noble, Michael S; Paull, Evan; Rao, Arvind; Reynolds, Sheila; Saksena, Gordon; Sanborn, Zack; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Shen, Ronglai; Shmulevich, Ilya; Sinha, Rileen; Stuart, Josh; Sumer, S Onur; Sun, Yichao; Tasman, Natalie; Taylor, Barry S; Voet, Doug; Weinhold, Nils; Weinstein, John N; Yang, Da; Yoshihara, Kosuke; Zheng, Siyuan; Zhang, Wei; Zou, Lihua; Abel, Ty; Sadeghi, Sara; Cohen, Mark L; Eschbacher, Jenny; Hattab, Eyas M; Raghunathan, Aditya; Schniederjan, Matthew J; Aziz, Dina; Barnett, Gene; Barrett, Wendi; Bigner, Darell D; Boice, Lori; Brewer, Cathy; Calatozzolo, Chiara; Campos, Benito; Carlotti, Carlos Gilberto; Chan, Timothy A; Cuppini, Lucia; Curley, Erin; Cuzzubbo, Stefania; Devine, Karen; DiMeco, Francesco; Duell, Rebecca; Elder, J Bradley; Fehrenbach, Ashley; Finocchiaro, Gaetano; Friedman, William; Fulop, Jordonna; Gardner, Johanna; Hermes, Beth; Herold-Mende, Christel; Jungk, Christine; Kendler, Ady; Lehman, Norman L; Lipp, Eric; Liu, Ouida; Mandt, Randy; McGraw, Mary; Mclendon, Roger; McPherson, Christopher; Neder, Luciano; Nguyen, Phuong; Noss, Ardene; Nunziata, Raffaele; Ostrom, Quinn T; Palmer, Cheryl; Perin, Alessandro; Pollo, Bianca; Potapov, Alexander; Potapova, Olga; Rathmell, W Kimryn; Rotin, Daniil; Scarpace, Lisa; Schilero, Cathy; Senecal, Kelly; Shimmel, Kristen; Shurkhay, Vsevolod; Sifri, Suzanne; Singh, Rosy; Sloan, Andrew E; Smolenski, Kathy; Staugaitis, Susan M; Steele, Ruth; Thorne, Leigh; Tirapelli, Daniela P C; Unterberg, Andreas; Vallurupalli, Mahitha; Wang, Yun; Warnick, Ronald; Williams, Felicia; Wolinsky, Yingli; Bell, Sue; Rosenberg, Mara; Stewart, Chip; Huang, Franklin; Grimsby, Jonna L; Radenbaugh, Amie J; Zhang, Jianan

    2015-06-25

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most

  13. Evolutionary time-scale of the begomoviruses: evidence from integrated sequences in the Nicotiana genome.

    Directory of Open Access Journals (Sweden)

    Pierre Lefeuvre

    Full Text Available Despite having single stranded DNA genomes that are replicated by host DNA polymerases, viruses in the family Geminiviridae are apparently evolving as rapidly as some RNA viruses. The observed substitution rates of geminiviruses in the genera Begomovirus and Mastrevirus are so high that the entire family could conceivably have originated less than a million years ago (MYA. However, the existence of geminivirus related DNA (GRD integrated within the genomes of various Nicotiana species suggests that the geminiviruses probably originated >10 MYA. Some have even suggested that a distinct New-World (NW lineage of begomoviruses may have arisen following the separation by continental drift of African and American proto-begomoviruses ∼110 MYA. We evaluate these various geminivirus origin hypotheses using Bayesian coalescent-based approaches to date firstly the Nicotiana GRD integration events, and then the divergence of the NW and Old-World (OW begomoviruses. Besides rejecting the possibility of a<2 MYA OW-NW begomovirus split, we could also discount that it may have occurred concomitantly with the breakup of Gondwanaland 110 MYA. Although we could only confidently narrow the date of the split down to between 2 and 80 MYA, the most plausible (and best supported date for the split is between 20 and 30 MYA--a time when global cooling ended the dispersal of temperate species between Asia and North America via the Beringian land bridge.

  14. Integrative Functional Genomics for Systems Genetics in GeneWeaver.org.

    Science.gov (United States)

    Bubier, Jason A; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

    2017-01-01

    The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data. GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets. These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org. Data are analyzed using statistical tools and advanced graph algorithms to discover new relations, prioritize candidate genes, and generate function hypotheses. Here we use GeneWeaver to find genes common to multiple gene sets, prioritize candidate genes from a quantitative trait locus, and characterize a set of differentially expressed genes. Coupling a large multispecies repository curated and empirical functional genomics data to fast computational tools allows for the rapid integrative analysis of heterogeneous data for interpreting and extrapolating systems genetics results.

  15. Integration models: multicultural and liberal approaches confronted

    Science.gov (United States)

    Janicki, Wojciech

    2012-01-01

    European societies have been shaped by their Christian past, upsurge of international migration, democratic rule and liberal tradition rooted in religious tolerance. Boosting globalization processes impose new challenges on European societies, striving to protect their diversity. This struggle is especially clearly visible in case of minorities trying to resist melting into mainstream culture. European countries' legal systems and cultural policies respond to these efforts in many ways. Respecting identity politics-driven group rights seems to be the most common approach, resulting in creation of a multicultural society. However, the outcome of respecting group rights may be remarkably contradictory to both individual rights growing out from liberal tradition, and to reinforced concept of integration of immigrants into host societies. The hereby paper discusses identity politics upturn in the context of both individual rights and integration of European societies.

  16. Introduction to solid mechanics an integrated approach

    CERN Document Server

    Lubliner, Jacob

    2014-01-01

    This textbook presents for the first time in one text the concepts and processes covered in statics and mechanics of materials curricula following a systematic, topically integrated approach. Since the turn of the millennium, it has become common in engineering schools to combine the traditional undergraduate offerings in rigid-body statics (usually called “statics”) and deformable body mechanics (known traditionally as “strength of materials” or, more recently, “mechanics of materials”) into a single, introductory course in solid mechanics. Many textbooks for the new course sequentially meld pieces of existing, discrete books—sometimes, but not always, acknowledging the origin—into two halves covering Statics and Mechanics of Materials. In this volume, Professors Lubliner and Papadopoulos methodically combine the essentials of statics and mechanics of materials, illustrating the relationship of concepts throughout, into one "integrated" text. This book also: ·         Offers thorough...

  17. Pedagogic process modeling: Humanistic-integrative approach

    Directory of Open Access Journals (Sweden)

    Boritko Nikolaj M.

    2007-01-01

    Full Text Available The paper deals with some current problems of modeling the dynamics of the subject-features development of the individual. The term "process" is considered in the context of the humanistic-integrative approach, in which the principles of self education are regarded as criteria for efficient pedagogic activity. Four basic characteristics of the pedagogic process are pointed out: intentionality reflects logicality and regularity of the development of the process; discreteness (stageability in dicates qualitative stages through which the pedagogic phenomenon passes; nonlinearity explains the crisis character of pedagogic processes and reveals inner factors of self-development; situationality requires a selection of pedagogic conditions in accordance with the inner factors, which would enable steering the pedagogic process. Offered are two steps for singling out a particular stage and the algorithm for developing an integrative model for it. The suggested conclusions might be of use for further theoretic research, analyses of educational practices and for realistic predicting of pedagogical phenomena. .

  18. FUPOL: an Integrated Approach to Participative Policies

    Directory of Open Access Journals (Sweden)

    Silvana Tomic Rotim

    2014-05-01

    Full Text Available The Future Policy Modelling Project (FUPOL is a research project funded by the 7th framework program of the European Union. Its research focus are new technologies and methods for e-governance, e-participation and policy modelling. The FUPOL consortium consists of partners from European countries, China and Kenya. and comprises innovative multinational companies, leading research institutes, high-level political organizations as well as strong pilot partners. This paper describes the FUPOL new integrated approach to policy design and implementation including also specific examples from real life pilots in cities from different countries. FUPOL consists of an advanced policy lifecycle and an IT-solution with features supporting all phases of the proposed lifecycle. The FUPOL concept and functional modules as well as the technical architecture to achieve such a complete integration are described.

  19. Experimental Approaches to Study Genome Packaging of Influenza A Viruses

    Directory of Open Access Journals (Sweden)

    Catherine Isel

    2016-08-01

    Full Text Available The genome of influenza A viruses (IAV consists of eight single-stranded negative sense viral RNAs (vRNAs encapsidated into viral ribonucleoproteins (vRNPs. It is now well established that genome packaging (i.e., the incorporation of a set of eight distinct vRNPs into budding viral particles, follows a specific pathway guided by segment-specific cis-acting packaging signals on each vRNA. However, the precise nature and function of the packaging signals, and the mechanisms underlying the assembly of vRNPs into sub-bundles in the cytoplasm and their selective packaging at the viral budding site, remain largely unknown. Here, we review the diverse and complementary methods currently being used to elucidate these aspects of the viral cycle. They range from conventional and competitive reverse genetics, single molecule imaging of vRNPs by fluorescence in situ hybridization (FISH and high-resolution electron microscopy and tomography of budding viral particles, to solely in vitro approaches to investigate vRNA-vRNA interactions at the molecular level.

  20. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas.

    Directory of Open Access Journals (Sweden)

    Priscila Daniele Ramos Cirilo

    Full Text Available Uterine Leiomyomas (ULs are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs. Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC and gene expression microarrays (SAM. The CONEXIC algorithm was applied to integrate the data.The integrated analysis identified the top 30 significant genes (P<0.01, which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively and IGFBP5 (P = 0.0002 and P = 0.006, respectively were up-regulated in the tumours when compared with the adjacent normal myometrium.The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.

  1. 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

  2. Brassica ASTRA: an integrated database for Brassica genomic research.

    Science.gov (United States)

    Love, Christopher G; Robinson, Andrew J; Lim, Geraldine A C; Hopkins, Clare J; Batley, Jacqueline; Barker, Gary; Spangenberg, German C; Edwards, David

    2005-01-01

    Brassica ASTRA is a public database for genomic information on Brassica species. The database incorporates expressed sequences with Swiss-Prot and GenBank comparative sequence annotation as well as secondary Gene Ontology (GO) annotation derived from the comparison with Arabidopsis TAIR GO annotations. Simple sequence repeat molecular markers are identified within resident sequences and mapped onto the closely related Arabidopsis genome sequence. Bacterial artificial chromosome (BAC) end sequences derived from the Multinational Brassica Genome Project are also mapped onto the Arabidopsis genome sequence enabling users to identify candidate Brassica BACs corresponding to syntenic regions of Arabidopsis. This information is maintained in a MySQL database with a web interface providing the primary means of interrogation. The database is accessible at http://hornbill.cspp.latrobe.edu.au.

  3. Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles.

    Science.gov (United States)

    Stepanauskas, Ramunas; Fergusson, Elizabeth A; Brown, Joseph; Poulton, Nicole J; Tupper, Ben; Labonté, Jessica M; Becraft, Eric D; Brown, Julia M; Pachiadaki, Maria G; Povilaitis, Tadas; Thompson, Brian P; Mascena, Corianna J; Bellows, Wendy K; Lubys, Arvydas

    2017-07-20

    Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.

  4. Integrate genome-based assessment of safety for probiotic strains: Bacillus coagulans GBI-30, 6086 as a case study.

    Science.gov (United States)

    Salvetti, Elisa; Orrù, Luigi; Capozzi, Vittorio; Martina, Alessia; Lamontanara, Antonella; Keller, David; Cash, Howard; Felis, Giovanna E; Cattivelli, Luigi; Torriani, Sandra; Spano, Giuseppe

    2016-05-01

    Probiotics are microorganisms that confer beneficial effects on the host; nevertheless, before being allowed for human consumption, their safety must be verified with accurate protocols. In the genomic era, such procedures should take into account the genomic-based approaches. This study aims at assessing the safety traits of Bacillus coagulans GBI-30, 6086 integrating the most updated genomics-based procedures and conventional phenotypic assays. Special attention was paid to putative virulence factors (VF), antibiotic resistance (AR) genes and genes encoding enzymes responsible for harmful metabolites (i.e. biogenic amines, BAs). This probiotic strain was phenotypically resistant to streptomycin and kanamycin, although the genome analysis suggested that the AR-related genes were not easily transferrable to other bacteria, and no other genes with potential safety risks, such as those related to VF or BA production, were retrieved. Furthermore, no unstable elements that could potentially lead to genomic rearrangements were detected. Moreover, a workflow is proposed to allow the proper taxonomic identification of a microbial strain and the accurate evaluation of risk-related gene traits, combining whole genome sequencing analysis with updated bioinformatics tools and standard phenotypic assays. The workflow presented can be generalized as a guideline for the safety investigation of novel probiotic strains to help stakeholders (from scientists to manufacturers and consumers) to meet regulatory requirements and avoid misleading information.

  5. APPROACH FOR IMPROVING THE INTEGRATED SENSOR ORIENTATION

    Directory of Open Access Journals (Sweden)

    E. Mitishita

    2016-06-01

    Full Text Available The direct determination of exterior orientation parameters (EOP of aerial images via integration of the Inertial Measurement Unit (IMU and GPS is often used in photogrammetric mapping nowadays. The accuracies of the EOP depend on the accurate parameters related to sensors mounting when the job is performed (offsets of the IMU relative to the projection centre and the angles of boresigth misalignment between the IMU and the photogrammetric coordinate system. In principle, when the EOP values do not achieve the required accuracies for the photogrammetric application, the approach, known as Integrated Sensor Orientation (ISO, is used to refine the direct EOP. ISO approach requires accurate Interior Orientation Parameters (IOP and standard deviation of the EOP under flight condition. This paper investigates the feasibility of use the in situ camera calibration to obtain these requirements. The camera calibration uses a small sub block of images, extracted from the entire block. A digital Vexcel UltraCam XP camera connected to APPLANIX POS AVTM system was used to get two small blocks of images that were use in this study. The blocks have different flight heights and opposite flight directions. The proposed methodology improved significantly the vertical and horizontal accuracies of the 3D point intersection. Using a minimum set of control points, the horizontal and vertical accuracies achieved nearly one image pixel of resolution on the ground (GSD. The experimental results are shown and discussed.

  6. Integrating Diverse Types of Genomic Data to Identify Genes that Underlie Adverse Pregnancy Phenotypes.

    Directory of Open Access Journals (Sweden)

    Jibril Hirbo

    Full Text Available Progress in understanding complex genetic diseases has been bolstered by synthetic approaches that overlay diverse data types and analyses to identify functionally important genes. Pre-term birth (PTB, a major complication of pregnancy, is a leading cause of infant mortality worldwide. A major obstacle in addressing PTB is that the mechanisms controlling parturition and birth timing remain poorly understood. Integrative approaches that overlay datasets derived from comparative genomics with function-derived ones have potential to advance our understanding of the genetics of birth timing, and thus provide insights into the genes that may contribute to PTB. We intersected data from fast evolving coding and non-coding gene regions in the human and primate lineage with data from genes expressed in the placenta, from genes that show enriched expression only in the placenta, as well as from genes that are differentially expressed in four distinct PTB clinical subtypes. A large fraction of genes that are expressed in placenta, and differentially expressed in PTB clinical subtypes (23-34% are fast evolving, and are associated with functions that include adhesion neurodevelopmental and immune processes. Functional categories of genes that express fast evolution in coding regions differ from those linked to fast evolution in non-coding regions. Finally, there is a surprising lack of overlap between fast evolving genes that are differentially expressed in four PTB clinical subtypes. Integrative approaches, especially those that incorporate evolutionary perspectives, can be successful in identifying potential genetic contributions to complex genetic diseases, such as PTB.

  7. Joint Genome Institute's Automation Approach and History

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Simon

    2006-07-05

    Department of Energy/Joint Genome Institute (DOE/JGI) collaborates with DOE national laboratories and community users, to advance genome science in support of the DOE missions of clean bio-energy, carbon cycling, and bioremediation.

  8. Healing and Preventing Pain: Complementary and Integrative Approaches

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Pain Management Healing and Preventing Pain, Complementary and Integrative Approaches Past ... Pain Management" Articles Putting A Pause In Pain / Healing and Preventing Pain Complementary and Integrative Approaches / Pain ...

  9. Integration of Genome-Wide TF Binding and Gene Expression Data to Characterize Gene Regulatory Networks in Plant Development.

    Science.gov (United States)

    Chen, Dijun; Kaufmann, Kerstin

    2017-01-01

    Key transcription factors (TFs) controlling the morphogenesis of flowers and leaves have been identified in the model plant Arabidopsis thaliana. Recent genome-wide approaches based on chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) enable systematic identification of genome-wide TF binding sites (TFBSs) of these regulators. Here, we describe a computational pipeline for analyzing ChIP-seq data to identify TFBSs and to characterize gene regulatory networks (GRNs) with applications to the regulatory studies of flower development. In particular, we provide step-by-step instructions on how to download, analyze, visualize, and integrate genome-wide data in order to construct GRNs for beginners of bioinformatics. The practical guide presented here is ready to apply to other similar ChIP-seq datasets to characterize GRNs of interest.

  10. Construction of reference chromosome-scale pseudomolecules for potato: integrating the potato genome with genetic and physical maps.

    Science.gov (United States)

    Sharma, Sanjeev Kumar; Bolser, Daniel; de Boer, Jan; Sønderkær, Mads; Amoros, Walter; Carboni, Martin Federico; D'Ambrosio, Juan Martín; de la Cruz, German; Di Genova, Alex; Douches, David S; Eguiluz, Maria; Guo, Xiao; Guzman, Frank; Hackett, Christine A; Hamilton, John P; Li, Guangcun; Li, Ying; Lozano, Roberto; Maass, Alejandro; Marshall, David; Martinez, Diana; McLean, Karen; Mejía, Nilo; Milne, Linda; Munive, Susan; Nagy, Istvan; Ponce, Olga; Ramirez, Manuel; Simon, Reinhard; Thomson, Susan J; Torres, Yerisf; Waugh, Robbie; Zhang, Zhonghua; Huang, Sanwen; Visser, Richard G F; Bachem, Christian W B; Sagredo, Boris; Feingold, Sergio E; Orjeda, Gisella; Veilleux, Richard E; Bonierbale, Merideth; Jacobs, Jeanne M E; Milbourne, Dan; Martin, David Michael Alan; Bryan, Glenn J

    2013-11-06

    The genome of potato, a major global food crop, was recently sequenced. The work presented here details the integration of the potato reference genome (DM) with a new sequence-tagged site marker-based linkage map and other physical and genetic maps of potato and the closely related species tomato. Primary anchoring of the DM genome assembly was accomplished by the use of a diploid segregating population, which was genotyped with several types of molecular genetic markers to construct a new ~936 cM linkage map comprising 2469 marker loci. In silico anchoring approaches used genetic and physical maps from the diploid potato genotype RH89-039-16 (RH) and tomato. This combined approach has allowed 951 superscaffolds to be ordered into pseudomolecules corresponding to the 12 potato chromosomes. These pseudomolecules represent 674 Mb (~93%) of the 723 Mb genome assembly and 37,482 (~96%) of the 39,031 predicted genes. The superscaffold order and orientation within the pseudomolecules are closely collinear with independently constructed high density linkage maps. Comparisons between marker distribution and physical location reveal regions of greater and lesser recombination, as well as regions exhibiting significant segregation distortion. The work presented here has led to a greatly improved ordering of the potato reference genome superscaffolds into chromosomal "pseudomolecules".

  11. The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

    Directory of Open Access Journals (Sweden)

    Adam Alexander Thil Smith

    2012-05-01

    Full Text Available Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes, a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short. The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.

  12. Role of Shwachman-Bodian-Diamond syndrome protein in translation machinery and cell chemotaxis: a comparative genomics approach

    Directory of Open Access Journals (Sweden)

    Vasieva O

    2011-09-01

    Full Text Available Olga VasievaInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; Fellowship for the Interpretation of Genomes, Burr Ridge, IL, USAAbstract: Shwachman-Bodian-Diamond syndrome (SBDS is linked to a mutation in a single gene. The SBDS proinvolved in RNA metabolism and ribosome-associated functions, but SBDS mutation is primarily linked to a defect in polymorphonuclear leukocytes unable to orient correctly in a spatial gradient of chemoattractants. Results of data mining and comparative genomic approaches undertaken in this study suggest that SBDS protein is also linked to tRNA metabolism and translation initiation. Analysis of crosstalk between translation machinery and cytoskeletal dynamics provides new insights into the cellular chemotactic defects caused by SBDS protein malfunction. The proposed functional interactions provide a new approach to exploit potential targets in the treatment and monitoring of this disease.Keywords: Shwachman-Bodian-Diamond syndrome, wybutosine, tRNA, chemotaxis, translation, genomics, gene proximity

  13. CoryneCenter – An online resource for the integrated analysis of corynebacterial genome and transcriptome data

    Directory of Open Access Journals (Sweden)

    Hüser Andrea T

    2007-11-01

    Full Text Available Abstract Background The introduction of high-throughput genome sequencing and post-genome analysis technologies, e.g. DNA microarray approaches, has created the potential to unravel and scrutinize complex gene-regulatory networks on a large scale. The discovery of transcriptional regulatory interactions has become a major topic in modern functional genomics. Results To facilitate the analysis of gene-regulatory networks, we have developed CoryneCenter, a web-based resource for the systematic integration and analysis of genome, transcriptome, and gene regulatory information for prokaryotes, especially corynebacteria. For this purpose, we extended and combined the following systems into a common platform: (1 GenDB, an open source genome annotation system, (2 EMMA, a MAGE compliant application for high-throughput transcriptome data storage and analysis, and (3 CoryneRegNet, an ontology-based data warehouse designed to facilitate the reconstruction and analysis of gene regulatory interactions. We demonstrate the potential of CoryneCenter by means of an application example. Using microarray hybridization data, we compare the gene expression of Corynebacterium glutamicum under acetate and glucose feeding conditions: Known regulatory networks are confirmed, but moreover CoryneCenter points out additional regulatory interactions. Conclusion CoryneCenter provides more than the sum of its parts. Its novel analysis and visualization features significantly simplify the process of obtaining new biological insights into complex regulatory systems. Although the platform currently focusses on corynebacteria, the integrated tools are by no means restricted to these species, and the presented approach offers a general strategy for the analysis and verification of gene regulatory networks. CoryneCenter provides freely accessible projects with the underlying genome annotation, gene expression, and gene regulation data. The system is publicly available at http://www.CoryneCenter.de.

  14. Integrating population genetics and conservation biology in the era of genomics.

    Science.gov (United States)

    Ouborg, N Joop

    2010-02-23

    As one of the final activities of the ESF-CONGEN Networking programme, a conference entitled 'Integrating Population Genetics and Conservation Biology' was held at Trondheim, Norway, from 23 to 26 May 2009. Conference speakers and poster presenters gave a display of the state-of-the-art developments in the field of conservation genetics. Over the five-year running period of the successful ESF-CONGEN Networking programme, much progress has been made in theoretical approaches, basic research on inbreeding depression and other genetic processes associated with habitat fragmentation and conservation issues, and with applying principles of conservation genetics in the conservation of many species. Future perspectives were also discussed in the conference, and it was concluded that conservation genetics is evolving into conservation genomics, while at the same time basic and applied research on threatened species and populations from a population genetic point of view continues to be emphasized.

  15. 2. Gestaltdrama as an Integrative Psychotherapeutic Approach

    Directory of Open Access Journals (Sweden)

    Polínek Martin Dominik

    2016-03-01

    Full Text Available The following text is an overview study which defines the basic phenomena and effective factors of Gestalt drama and outlines some of the researches carried out in this area by the author during recent years. Gestalt drama is the name of a specific psychotherapeutic approach applied by the author in his practice, which combines Gestalt therapy with expressive approaches (especially with dramatherapy, theatrotherapy and fairytale-therapy. Linking Gestalt therapy and expressive techniques results in a specific psychotherapeutic approach whose versatility and holistic conception makes it suitable not only for psychotherapy but also for self-development of people with special needs, as it has the potential to meet the higher psychological needs even when the lower needs are not sufficiently saturated. The article further presents the interpretation of the partial results of research focusing on the analysis of integration performance where gestaltdrama techniques have been applied. These performances resulted from one-day dramatherapy workshops with clients suffering from mental retardation and with clients with behavioural disorders. This includes the analysis of differences between dramatical expression within the above target groups.

  16. 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.

  17. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Agnelli Luca

    2008-08-01

    Full Text Available Abstract Background The role of microRNAs (miRNAs in multiple myeloma (MM has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs and focused on transcripts whose expression varied significantly across the dataset. Methods miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets. Results We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and

  18. Omics and Environmental Science Genomic Approaches With Natural Fish Populations From Polluted Environments

    Science.gov (United States)

    Bozinovic, Goran; Oleksiak, Marjorie F.

    2010-01-01

    Transcriptomics and population genomics are two complementary genomic approaches that can be used to gain insight into pollutant effects in natural populations. Transcriptomics identify altered gene expression pathways while population genomics approaches more directly target the causative genomic polymorphisms. Neither approach is restricted to a pre-determined set of genes or loci. Instead, both approaches allow a broad overview of genomic processes. Transcriptomics and population genomic approaches have been used to explore genomic responses in populations of fish from polluted environments and have identified sets of candidate genes and loci that appear biologically important in response to pollution. Often differences in gene expression or loci between polluted and reference populations are not conserved among polluted populations suggesting a biological complexity that we do not yet fully understand. As genomic approaches become less expensive with the advent of new sequencing and genotyping technologies, they will be more widely used in complimentary studies. However, while these genomic approaches are immensely powerful for identifying candidate gene and loci, the challenge of determining biological mechanisms that link genotypes and phenotypes remains. PMID:21072843

  19. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

    2011-01-01

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

  20. Permutation statistical methods an integrated approach

    CERN Document Server

    Berry, Kenneth J; Johnston, Janis E

    2016-01-01

    This research monograph provides a synthesis of a number of statistical tests and measures, which, at first consideration, appear disjoint and unrelated. Numerous comparisons of permutation and classical statistical methods are presented, and the two methods are compared via probability values and, where appropriate, measures of effect size. Permutation statistical methods, compared to classical statistical methods, do not rely on theoretical distributions, avoid the usual assumptions of normality and homogeneity of variance, and depend only on the data at hand. This text takes a unique approach to explaining statistics by integrating a large variety of statistical methods, and establishing the rigor of a topic that to many may seem to be a nascent field in statistics. This topic is new in that it took modern computing power to make permutation methods available to people working in the mainstream of research. This research monograph addresses a statistically-informed audience, and can also easily serve as a ...

  1. Thermodynamics and statistical mechanics an integrated approach

    CERN Document Server

    Shell, M Scott

    2015-01-01

    Learn classical thermodynamics alongside statistical mechanics with this fresh approach to the subjects. Molecular and macroscopic principles are explained in an integrated, side-by-side manner to give students a deep, intuitive understanding of thermodynamics and equip them to tackle future research topics that focus on the nanoscale. Entropy is introduced from the get-go, providing a clear explanation of how the classical laws connect to the molecular principles, and closing the gap between the atomic world and thermodynamics. Notation is streamlined throughout, with a focus on general concepts and simple models, for building basic physical intuition and gaining confidence in problem analysis and model development. Well over 400 guided end-of-chapter problems are included, addressing conceptual, fundamental, and applied skill sets. Numerous worked examples are also provided together with handy shaded boxes to emphasize key concepts, making this the complete teaching package for students in chemical engineer...

  2. Stakeholder interaction within the ERICA Integrated Approach.

    Science.gov (United States)

    Zinger, I; Oughton, D H; Jones, S R

    2008-09-01

    Within the ERICA project, stakeholder involvement has been addressed within three main areas: generic interactions throughout the project, specific consultation by means of attendance to events and considerations as part of the ERICA Integrated Approach and Assessment Tool. The word stakeholders meant namely any individual or group who may be affected by or have an interest in an issue, and to include experts, lay-people and the public. An End-Users-Group (EUG) was set up to facilitate the two-way dialogue between the ERICA Consortium and stakeholders. The ERICA EUG consisted of representatives of 60 organisations ranging from regulatory bodies, national advisory bodies, academia, non-governmental organisations, industry, consultants and inter-governmental organisations. Stakeholder interaction was included from the very start of the project. Inputs from the EUG were recorded and in most instances incorporated within the development of the project and thus influenced and helped to shape some of the ERICA deliverables.

  3. MODELS OF TECHNOLOGY ADOPTION: AN INTEGRATIVE APPROACH

    Directory of Open Access Journals (Sweden)

    Andrei OGREZEANU

    2015-06-01

    Full Text Available The interdisciplinary study of information technology adoption has developed rapidly over the last 30 years. Various theoretical models have been developed and applied such as: the Technology Acceptance Model (TAM, Innovation Diffusion Theory (IDT, Theory of Planned Behavior (TPB, etc. The result of these many years of research is thousands of contributions to the field, which, however, remain highly fragmented. This paper develops a theoretical model of technology adoption by integrating major theories in the field: primarily IDT, TAM, and TPB. To do so while avoiding mess, an approach that goes back to basics in independent variable type’s development is proposed; emphasizing: 1 the logic of classification, and 2 psychological mechanisms behind variable types. Once developed these types are then populated with variables originating in empirical research. Conclusions are developed on which types are underpopulated and present potential for future research. I end with a set of methodological recommendations for future application of the model.

  4. Integrating systems Approaches into Pharmaceutical Sciences

    DEFF Research Database (Denmark)

    Westerhoff, H.V.; Mosekilde, Erik; Noe, C. R.

    2008-01-01

    During the first week of December 2007, the European Federation for Pharmaceutical Sciences (EUFEPS) and BioSim, the major European Network of Excellence on Systems Biology, held a challenging conference on the use of mathematical models in the drug development process. More precisely, the purpose...... of the conference was to promote the ‘Integration of Systems Approaches into Pharmaceutical Sciences’ in view of optimising the development of new effective drugs. And a challenge this is, considering both the high attrition rates in the pharmaceutical industry and the failure of finding definitive drug solutions...... for many of the diseases that plague mankind today. The conference was co-sponsored by the American College of Clinical Pharmacology, the European Center for Pharmaceutical Medicine, and the Swiss Society of Pharmaceutical Sciences and, besides representatives from the European Regulatory Agencies and FDA...

  5. Systematic Approach to Better Understanding Integration Costs

    Energy Technology Data Exchange (ETDEWEB)

    Stark, Gregory B. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-09-01

    This research presents a systematic approach to evaluating the costs of integrating new generation and operational procedures into an existing power system, and the methodology is independent of the type of change or nature of the generation. The work was commissioned by the U.S. Department of Energy and performed by the National Renewable Energy Laboratory to investigate three integration cost-related questions: (1) How does the addition of new generation affect a system's operational costs, (2) How do generation mix and operating parameters and procedures affect costs, and (3) How does the amount of variable generation (non-dispatchable wind and solar) impact the accuracy of natural gas orders? A detailed operational analysis was performed for seven sets of experiments: variable generation, large conventional generation, generation mix, gas prices, fast-start generation, self-scheduling, and gas supply constraints. For each experiment, four components of integration costs were examined: cycling costs, non-cycling VO&M costs, fuel costs, and reserves provisioning costs. The investigation was conducted with PLEXOS production cost modeling software utilizing an updated version of the Institute of Electrical and Electronics Engineers 118-bus test system overlaid with projected operating loads from the Western Electricity Coordinating Council for the Sacramento Municipal Utility District, Puget Sound Energy, and Public Service Colorado in the year 2020. The test system was selected in consultation with an industry-based technical review committee to be a reasonable approximation of an interconnection yet small enough to allow the research team to investigate a large number of scenarios and sensitivity combinations. The research should prove useful to market designers, regulators, utilities, and others who want to better understand how system changes can affect production costs.

  6. Quantum gravitation. The Feynman path integral approach

    International Nuclear Information System (INIS)

    Hamber, Herbert W.

    2009-01-01

    The book covers the theory of Quantum Gravitation from the point of view of Feynman path integrals. These provide a manifestly covariant approach in which fundamental quantum aspects of the theory such as radiative corrections and the renormalization group can be systematically and consistently addressed. The path integral method is suitable for both perturbative as well as non-perturbative studies, and is known to already provide a framework of choice for the theoretical investigation of non-abelian gauge theories, the basis for three of the four known fundamental forces in nature. The book thus provides a coherent outline of the present status of the theory gravity based on Feynman's formulation, with an emphasis on quantitative results. Topics are organized in such a way that the correspondence to similar methods and results in modern gauge theories becomes apparent. Covariant perturbation theory are developed using the full machinery of Feynman rules, gauge fixing, background methods and ghosts. The renormalization group for gravity and the existence of non-trivial ultraviolet fixed points are investigated, stressing a close correspondence with well understood statistical field theory models. Later the lattice formulation of gravity is presented as an essential tool towards an understanding of key features of the non-perturbative vacuum. The book ends with a discussion of contemporary issues in quantum cosmology such as scale dependent gravitational constants and quantum effects in the early universe. (orig.)

  7. Novel approach for deriving genome wide SNP analysis data from archived blood spots

    Science.gov (United States)

    2012-01-01

    Background The ability to transport and store DNA at room temperature in low volumes has the advantage of optimising cost, time and storage space. Blood spots on adapted filter papers are popular for this, with FTA (Flinders Technology Associates) Whatman™TM technology being one of the most recent. Plant material, plasmids, viral particles, bacteria and animal blood have been stored and transported successfully using this technology, however the method of porcine DNA extraction from FTA Whatman™TM cards is a relatively new approach, allowing nucleic acids to be ready for downstream applications such as PCR, whole genome amplification, sequencing and subsequent application to single nucleotide polymorphism microarrays has hitherto been under-explored. Findings DNA was extracted from FTA Whatman™TM cards (following adaptations of the manufacturer’s instructions), whole genome amplified and subsequently analysed to validate the integrity of the DNA for downstream SNP analysis. DNA was successfully extracted from 288/288 samples and amplified by WGA. Allele dropout post WGA, was observed in less than 2% of samples and there was no clear evidence of amplification bias nor contamination. Acceptable call rates on porcine SNP chips were also achieved using DNA extracted and amplified in this way. Conclusions DNA extracted from FTA Whatman cards is of a high enough quality and quantity following whole genomic amplification to perform meaningful SNP chip studies. PMID:22974252

  8. Modeling the integration of bacterial rRNA fragments into the human cancer genome.

    Science.gov (United States)

    Sieber, Karsten B; Gajer, Pawel; Dunning Hotopp, Julie C

    2016-03-21

    Cancer is a disease driven by the accumulation of genomic alterations, including the integration of exogenous DNA into the human somatic genome. We previously identified in silico evidence of DNA fragments from a Pseudomonas-like bacteria integrating into the 5'-UTR of four proto-oncogenes in stomach cancer sequencing data. The functional and biological consequences of these bacterial DNA integrations remain unknown. Modeling of these integrations suggests that the previously identified sequences cover most of the sequence flanking the junction between the bacterial and human DNA. Further examination of these reads reveals that these integrations are rich in guanine nucleotides and the integrated bacterial DNA may have complex transcript secondary structures. The models presented here lay the foundation for future experiments to test if bacterial DNA integrations alter the transcription of the human genes.

  9. Putative bacterial interactions from metagenomic knowledge with an integrative systems ecology approach.

    Science.gov (United States)

    Bordron, Philippe; Latorre, Mauricio; Cortés, Maria-Paz; González, Mauricio; Thiele, Sven; Siegel, Anne; Maass, Alejandro; Eveillard, Damien

    2016-02-01

    Following the trend of studies that investigate microbial ecosystems using different metagenomic techniques, we propose a new integrative systems ecology approach that aims to decipher functional roles within a consortium through the integration of genomic and metabolic knowledge at genome scale. For the sake of application, using public genomes of five bacterial strains involved in copper bioleaching: Acidiphilium cryptum, Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, Leptospirillum ferriphilum, and Sulfobacillus thermosulfidooxidans, we first reconstructed a global metabolic network. Next, using a parsimony assumption, we deciphered sets of genes, called Sets from Genome Segments (SGS), that (1) are close on their respective genomes, (2) take an active part in metabolic pathways and (3) whose associated metabolic reactions are also closely connected within metabolic networks. Overall, this SGS paradigm depicts genomic functional units that emphasize respective roles of bacterial strains to catalyze metabolic pathways and environmental processes. Our analysis suggested that only few functional metabolic genes are horizontally transferred within the consortium and that no single bacterial strain can accomplish by itself the whole copper bioleaching. The use of SGS pinpoints a functional compartmentalization among the investigated species and exhibits putative bacterial interactions necessary for promoting these pathways. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  10. 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 ...

  11. An Integrated Genetic and Cytogenetic Map of the Cucumber Genome

    Science.gov (United States)

    The Cucurbitaceae includes important crops as cucumber, melon, watermelon, and 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 li...

  12. Integrated genome-based studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Tiedje, James M. [Michigan State Univ., East Lansing, MI (United States); Konstantinidis, Kostas [Michigan State Univ., East Lansing, MI (United States); Worden, Mark [Michigan State Univ., East Lansing, MI (United States)

    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.

  13. 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%) than...

  14. Pressure Shell Approach to Integrated Environmental Protection

    Science.gov (United States)

    Kennedy, Kriss J.

    2011-01-01

    The next generation of exploration mission human systems will require environmental protection such as radiation protection that is effective and efficient. In order to continue human exploration, habitat systems will require special shells to protect astronauts from hostile environments. The Pressure Shell Approach to integrated environmental (radiation) protection is a multi-layer shell that can be used for multifunctional environmental protection. Self-healing, self-repairing nano technologies and sensors are incorporated into the shell. This shell consists of multiple layers that can be tailored for specific environmental protection needs. Mainly, this innovation focuses on protecting crew from exposure to micrometeorites, thermal, solar flares, and galactic cosmic ray (GCR) radiation. The Pressure Shell Approach consists of a micrometeoroid and secondary ejecta protection layer; a thin, composite shell placed in between two layers that is non-structural; an open cavity layer that can be filled with water, regolith, or polyethylene foam; a thicker composite shell that is a structural load bearing that is placed between two layers; and a bladder coating on the interior composite shell. This multi-layer shell creates an effective radiation protection system. Most of its layers can be designed with the materials necessary for specific environments. In situ materials such as water or regolith can be added to the shell design for supplemental radiation protection.

  15. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu......The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

  16. A knowledge integration approach to flood vulnerability

    Science.gov (United States)

    Mazzorana, Bruno; Fuchs, Sven

    2014-05-01

    Understanding, qualifying and quantifying vulnerability is an essential need for implementing effective and efficient flood risk mitigation strategies; in particular if possible synergies between different mitigation alternatives, such as active and passive measures, should be achieved. In order to combine different risk management options it is necessary to take an interdisciplinary approach to vulnerability reduction, and as a result the affected society may be willing to accept a certain degree of self-responsibility. However, due to differing mono-disciplinary approaches and regional foci undertaken until now, different aspects of vulnerability to natural hazards in general and to floods in particular remain uncovered and as a result the developed management options remain sub-optimal. Taking an even more fundamental viewpoint, the empirical vulnerability functions used in risk assessment specifically fail to capture physical principles of the damage-generating mechanisms to the build environment. The aim of this paper is to partially close this gap by discussing a balanced knowledge integration approach which can be used to resolve the multidisciplinary disorder in flood vulnerability research. Modelling techniques such as mathematical-physical modelling of the flood hazard impact to and response from the building envelope affected, and formative scenario analyses of possible consequences in terms of damage and loss are used in synergy to provide an enhanced understanding of vulnerability and to render the derived knowledge into interdisciplinary mitigation strategies. The outlined formal procedure allows for a convincing knowledge alignment of quantified, but partial, information about vulnerability as a result of the application of physical and engineering notions and valuable, but often underspecified, qualitative argumentation strings emerging from the adopted socio-economic viewpoint.

  17. 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.

  18. A multi-objective constraint-based approach for modeling genome-scale microbial ecosystems.

    Science.gov (United States)

    Budinich, Marko; Bourdon, Jérémie; Larhlimi, Abdelhalim; Eveillard, Damien

    2017-01-01

    Interplay within microbial communities impacts ecosystems on several scales, and elucidation of the consequent effects is a difficult task in ecology. In particular, the integration of genome-scale data within quantitative models of microbial ecosystems remains elusive. This study advocates the use of constraint-based modeling to build predictive models from recent high-resolution -omics datasets. Following recent studies that have demonstrated the accuracy of constraint-based models (CBMs) for simulating single-strain metabolic networks, we sought to study microbial ecosystems as a combination of single-strain metabolic networks that exchange nutrients. This study presents two multi-objective extensions of CBMs for modeling communities: multi-objective flux balance analysis (MO-FBA) and multi-objective flux variability analysis (MO-FVA). Both methods were applied to a hot spring mat model ecosystem. As a result, multiple trade-offs between nutrients and growth rates, as well as thermodynamically favorable relative abundances at community level, were emphasized. We expect this approach to be used for integrating genomic information in microbial ecosystems. Following models will provide insights about behaviors (including diversity) that take place at the ecosystem scale.

  19. A multi-objective constraint-based approach for modeling genome-scale microbial ecosystems.

    Directory of Open Access Journals (Sweden)

    Marko Budinich

    Full Text Available Interplay within microbial communities impacts ecosystems on several scales, and elucidation of the consequent effects is a difficult task in ecology. In particular, the integration of genome-scale data within quantitative models of microbial ecosystems remains elusive. This study advocates the use of constraint-based modeling to build predictive models from recent high-resolution -omics datasets. Following recent studies that have demonstrated the accuracy of constraint-based models (CBMs for simulating single-strain metabolic networks, we sought to study microbial ecosystems as a combination of single-strain metabolic networks that exchange nutrients. This study presents two multi-objective extensions of CBMs for modeling communities: multi-objective flux balance analysis (MO-FBA and multi-objective flux variability analysis (MO-FVA. Both methods were applied to a hot spring mat model ecosystem. As a result, multiple trade-offs between nutrients and growth rates, as well as thermodynamically favorable relative abundances at community level, were emphasized. We expect this approach to be used for integrating genomic information in microbial ecosystems. Following models will provide insights about behaviors (including diversity that take place at the ecosystem scale.

  20. Group sparse canonical correlation analysis for genomic data integration.

    Science.gov (United States)

    Lin, Dongdong; Zhang, Jigang; Li, Jingyao; Calhoun, Vince D; Deng, Hong-Wen; Wang, Yu-Ping

    2013-08-12

    The emergence of high-throughput genomic datasets from different sources and platforms (e.g., gene expression, single nucleotide polymorphisms (SNP), and copy number variation (CNV)) has greatly enhanced our understandings of the interplay of these genomic factors as well as their influences on the complex diseases. It is challenging to explore the relationship between these different types of genomic data sets. In this paper, we focus on a multivariate statistical method, canonical correlation analysis (CCA) method for this problem. Conventional CCA method does not work effectively if the number of data samples is significantly less than that of biomarkers, which is a typical case for genomic data (e.g., SNPs). Sparse CCA (sCCA) methods were introduced to overcome such difficulty, mostly using penalizations with l-1 norm (CCA-l1) or the combination of l-1and l-2 norm (CCA-elastic net). However, they overlook the structural or group effect within genomic data in the analysis, which often exist and are important (e.g., SNPs spanning a gene interact and work together as a group). We propose a new group sparse CCA method (CCA-sparse group) along with an effective numerical algorithm to study the mutual relationship between two different types of genomic data (i.e., SNP and gene expression). We then extend the model to a more general formulation that can include the existing sCCA models. We apply the model to feature/variable selection from two data sets and compare our group sparse CCA method with existing sCCA methods on both simulation and two real datasets (human gliomas data and NCI60 data). We use a graphical representation of the samples with a pair of canonical variates to demonstrate the discriminating characteristic of the selected features. Pathway analysis is further performed for biological interpretation of those features. The CCA-sparse group method incorporates group effects of features into the correlation analysis while performs individual feature

  1. Data integration, systems approach and multilevel description of complex biosystems

    International Nuclear Information System (INIS)

    Hernández-Lemus, Enrique

    2013-01-01

    Recent years have witnessed the development of new quantitative approaches and theoretical tenets in the biological sciences. The advent of high throughput experiments in genomics, proteomics and electrophysiology (to cite just a few examples) have provided the researchers with unprecedented amounts of data to be analyzed. Large datasets, however can not provide the means to achieve a complete understanding of the underlying biological phenomena, unless they are supplied with a solid theoretical framework and with proper analytical tools. It is now widely accepted that by using and extending some of the paradigmatic principles of what has been called complex systems theory, some degree of advance in this direction can be attained. We will be presenting ways in which by using data integration techniques (linear, non-linear, combinatorial, graphical), multidimensional-multilevel descriptions (multifractal modeling, dimensionality reduction, computational learning), as well as an approach based in systems theory (interaction maps, probabilistic graphical models, non-equilibrium physics) have allowed us to better understand some problems in the interface of Statistical Physics and Computational Biology

  2. New Approaches and Technologies to Sequence de novo Plant reference Genomes (2013 DOE JGI Genomics of Energy and Environment 8th Annual User Meeting)

    Energy Technology Data Exchange (ETDEWEB)

    Schmutz, Jeremy

    2013-03-01

    Jeremy Schmutz of the HudsonAlpha Institute for Biotechnology on New approaches and technologies to sequence de novo plant reference genomes at the 8th Annual Genomics of Energy Environment Meeting on March 27, 2013 in Walnut Creek, CA.

  3. Integrated Approach to Reconstruction of Microbial Regulatory Networks

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A [Sanford-Burnham Medical Research Institute; Novichkov, Pavel S [Lawrence Berkeley National Laboratory

    2013-11-04

    This project had the goal(s) of development of integrated bioinformatics platform for genome-scale inference and visualization of transcriptional regulatory networks (TRNs) in bacterial genomes. The work was done in Sanford-Burnham Medical Research Institute (SBMRI, P.I. D.A. Rodionov) and Lawrence Berkeley National Laboratory (LBNL, co-P.I. P.S. Novichkov). The developed computational resources include: (1) RegPredict web-platform for TRN inference and regulon reconstruction in microbial genomes, and (2) RegPrecise database for collection, visualization and comparative analysis of transcriptional regulons reconstructed by comparative genomics. These analytical resources were selected as key components in the DOE Systems Biology KnowledgeBase (SBKB). The high-quality data accumulated in RegPrecise will provide essential datasets of reference regulons in diverse microbes to enable automatic reconstruction of draft TRNs in newly sequenced genomes. We outline our progress toward the three aims of this grant proposal, which were: Develop integrated platform for genome-scale regulon reconstruction; Infer regulatory annotations in several groups of bacteria and building of reference collections of microbial regulons; and Develop KnowledgeBase on microbial transcriptional regulation.

  4. 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.

  5. International regulatory landscape and integration of corrective genome editing into in vitro fertilization.

    Science.gov (United States)

    Araki, Motoko; Ishii, Tetsuya

    2014-11-24

    Genome editing technology, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, has enabled far more efficient genetic engineering even in non-human primates. This biotechnology is more likely to develop into medicine for preventing a genetic disease if corrective genome editing is integrated into assisted reproductive technology, represented by in vitro fertilization. Although rapid advances in genome editing are expected to make germline gene correction feasible in a clinical setting, there are many issues that still need to be addressed before this could occur. We herein examine current status of genome editing in mammalian embryonic stem cells and zygotes and discuss potential issues in the international regulatory landscape regarding human germline gene modification. Moreover, we address some ethical and social issues that would be raised when each country considers whether genome editing-mediated germline gene correction for preventive medicine should be permitted.

  6. Genomic and Functional Approaches to Understanding Cancer Aneuploidy

    NARCIS (Netherlands)

    Taylor, Alison M.; Shih, Juliann; Ha, Gavin; Gao, Galen F.; Zhang, Xiaoyang; Berger, Ashton C.; Schumacher, Steven E.; Wang, Chen; Hu, Hai; Liu, Jianfang; Lazar, Alexander J.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Angulo Gonzalez, Ana Maria; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, Jonathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Mora Pinero, Edna M.; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Cherniack, Andrew D.; Beroukhim, Rameen; Meyerson, Matthew

    2018-01-01

    Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was

  7. Adaptation of Lactococcus lactis to its environment : a genomics approach

    NARCIS (Netherlands)

    Zomer, Albertus Lambert

    2007-01-01

    This thesis describes a number of strategies of Lactococcus lactis to adapt to its ever-changing environment. Although the complete genome sequence of L. lactis subspecies lactis IL1403, became available when this research was started, the genome sequence of the lactic acid bacterial paradigm, L.

  8. Approaching the Sequential and Three-Dimensional Organization of Genomes

    NARCIS (Netherlands)

    T.A. Knoch (Tobias)

    2006-01-01

    textabstractGenomes are one of the major foundations of life due to their role in information storage, process regulation and evolution. To achieve a deeper unterstanding of the human genome the three-dimensional organization of the human cell nucleus, the structural-, scaling- and dynamic

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Statistical Viewer: a tool to upload and integrate linkage and association data as plots displayed within the Ensembl genome browser

    Directory of Open Access Journals (Sweden)

    Hauser Elizabeth R

    2005-04-01

    genes in private data tracks. Statistic View is a novel and powerful visual feature that enhances Ensembl's utility as valuable resource for integrative genomic-based approaches to the identification of candidate disease susceptibility genes. At present there are no other tools that provide for the visualization of 2-dimensional plots of quantitative data scores against genomic coordinates in the context of a primary public genome annotation browser.

  15. INVESTIGATIONS INTO MOLECULAR PATHWAYS IN THE POST GENOME ERA: CROSS SPECIES COMPARATIVE GENOMICS APPROACH

    Science.gov (United States)

    Genome sequencing efforts in the past decade were aimed at generating draft sequences of many prokaryotic and eukaryotic model organisms. Successful completion of unicellular eukaryotes, worm, fly and human genome have opened up the new field of molecular biology and function...

  16. Genotyping-by-sequencing for Populus population genomics: an assessment of genome sampling patterns and filtering approaches.

    Directory of Open Access Journals (Sweden)

    Martin P Schilling

    Full Text Available Continuing advances in nucleotide sequencing technology are inspiring a suite of genomic approaches in studies of natural populations. Researchers are faced with data management and analytical scales that are increasing by orders of magnitude. With such dramatic advances comes a need to understand biases and error rates, which can be propagated and magnified in large-scale data acquisition and processing. Here we assess genomic sampling biases and the effects of various population-level data filtering strategies in a genotyping-by-sequencing (GBS protocol. We focus on data from two species of Populus, because this genus has a relatively small genome and is emerging as a target for population genomic studies. We estimate the proportions and patterns of genomic sampling by examining the Populus trichocarpa genome (Nisqually-1, and demonstrate a pronounced bias towards coding regions when using the methylation-sensitive ApeKI restriction enzyme in this species. Using population-level data from a closely related species (P. tremuloides, we also investigate various approaches for filtering GBS data to retain high-depth, informative SNPs that can be used for population genetic analyses. We find a data filter that includes the designation of ambiguous alleles resulted in metrics of population structure and Hardy-Weinberg equilibrium that were most consistent with previous studies of the same populations based on other genetic markers. Analyses of the filtered data (27,910 SNPs also resulted in patterns of heterozygosity and population structure similar to a previous study using microsatellites. Our application demonstrates that technically and analytically simple approaches can readily be developed for population genomics of natural populations.

  17. Nuclear power programme planning: An integrated approach

    International Nuclear Information System (INIS)

    2001-12-01

    The International Atomic Energy Agency (IAEA) has published material on different policy considerations in the introduction of nuclear power, primarily addressed to top level decision makers in government and industry in Member States. Several Member States and experts recommended to the IAEA to address the aspects of an integrated approach to nuclear power programme planning and to serve as guidance to those countries wishing to embark on a nuclear power programme. As a follow-up, the present publication is primarily intended to serve as guidance for executives and managers in Member States in planning for possible introduction of nuclear power plants in their electricity generating systems. Nuclear power programme planning, as dealt with in this publication, includes all activities that need to be carried out up to a well-founded decision to proceed with a project feasibility study. Project implementation beyond this decision is not in the scope of this publication. Although it is possible to use nuclear energy as a heat source for industrial processes, desalination and other heat applications, it is assumed in this publication that the planning is aimed towards nuclear power for electricity generation. Much of the information given would, however, also be relevant for planning of nuclear reactors for heat production. The publication was prepared within the framework of the IAEA programme on nuclear power planning, implementation and performance as a joint activity of the Nuclear Power Engineering Section and the Planning and Economic Studies Section (Division of Nuclear Power)

  18. Graph-based semi-supervised learning with genomic data integration using condition-responsive genes applied to phenotype classification.

    Science.gov (United States)

    Doostparast Torshizi, Abolfazl; Petzold, Linda R

    2018-01-01

    Data integration methods that combine data from different molecular levels such as genome, epigenome, transcriptome, etc., have received a great deal of interest in the past few years. It has been demonstrated that the synergistic effects of different biological data types can boost learning capabilities and lead to a better understanding of the underlying interactions among molecular levels. In this paper we present a graph-based semi-supervised classification algorithm that incorporates latent biological knowledge in the form of biological pathways with gene expression and DNA methylation data. The process of graph construction from biological pathways is based on detecting condition-responsive genes, where 3 sets of genes are finally extracted: all condition responsive genes, high-frequency condition-responsive genes, and P-value-filtered genes. The proposed approach is applied to ovarian cancer data downloaded from the Human Genome Atlas. Extensive numerical experiments demonstrate superior performance of the proposed approach compared to other state-of-the-art algorithms, including the latest graph-based classification techniques. Simulation results demonstrate that integrating various data types enhances classification performance and leads to a better understanding of interrelations between diverse omics data types. The proposed approach outperforms many of the state-of-the-art data integration algorithms. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  19. A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    Pengpeng Ma

    2015-11-01

    Full Text Available Maternal genomic imprints are established during oogenesis. Histone deacetylases (HDACs 1 and 2 are required for oocyte development in mouse, but their role in genomic imprinting is unknown. We find that Hdac1:Hdac2−/− double-mutant growing oocytes exhibit global DNA hypomethylation and fail to establish imprinting marks for Igf2r, Peg3, and Srnpn. Global hypomethylation correlates with increased retrotransposon expression and double-strand DNA breaks. Nuclear-associated DNMT3A2 is reduced in double-mutant oocytes, and injecting these oocytes with Hdac2 partially restores DNMT3A2 nuclear staining. DNMT3A2 co-immunoprecipitates with HDAC2 in mouse embryonic stem cells. Partial loss of nuclear DNMT3A2 and HDAC2 occurs in Sin3a−/− oocytes, which exhibit decreased DNA methylation of imprinting control regions for Igf2r and Srnpn, but not Peg3. These results suggest seminal roles of HDAC1/2 in establishing maternal genomic imprints and maintaining genomic integrity in oocytes mediated in part through a SIN3A complex that interacts with DNMT3A2.

  20. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    Directory of Open Access Journals (Sweden)

    Beleut Manfred

    2012-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

  1. Safety in Schools: An Integral Approach

    Science.gov (United States)

    Gairin, Joaquin; Castro, Diego

    2011-01-01

    The present paper summarizes a research project into integral safety in schools. The aims of this particular research are, firstly, to evaluate the degree of integral safety in schools, secondly, to propose means for improving prevention and integral safety systems and thirdly, to identify the characteristics of safety culture. The field work was…

  2. Integration of association statistics over genomic regions using Bayesian adaptive regression splines

    Directory of Open Access Journals (Sweden)

    Zhang Xiaohua

    2003-11-01

    Full Text Available Abstract In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS. For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.

  3. An Assessment of Different Genomic Approaches for Inferring Phylogeny of Listeria monocytogenes

    DEFF Research Database (Denmark)

    Henri, Clementine; Leekitcharoenphon, Pimlapas; Carleton, Heather A.

    2017-01-01

    Background/objectives: Whole genome sequencing (WGS) has proven to be a powerful subtyping tool for foodborne pathogenic bacteria like L. monocytogenes. The interests of genome-scale analysis for national surveillance, outbreak detection or source tracking has been largely documented. The genomic......MLPPST) or pan genome (wgMLPPST). Currently, there are little comparisons studies of these different analytical approaches. Our objective was to assess and compare different genomic methods that can be implemented in order to cluster isolates of L monocytogenes.Methods: The clustering methods were evaluated...... on a collection of 207 L. monocytogenes genomes of food origin representative of the genetic diversity of the Anses collection. The trees were then compared using robust statistical analyses.Results: The backward comparability between conventional typing methods and genomic methods revealed a near...

  4. Numerical approach to one-loop integrals

    International Nuclear Information System (INIS)

    Fujimoto, Junpei; Shimizu, Yoshimitsu; Kato, Kiyoshi; Oyanagi, Yoshio.

    1992-01-01

    Two numerical methods are proposed for the calculation of one-loop scalar integrals. In the first method, the singularity is cancelled by the symmetrization of the integrand and the integration is done by a Monte-Carlo method. In the second one, after the transform of the integrand into a standard form, the integral is reduced into a regular numerical integral. These methods provide us practical tools to evaluate one-loop Feynman diagrams with desired numerical accuracy. They are extended to the integral with numerator and the treatment of the one-loop virtual correction to the cross section is also presented. (author)

  5. 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 G 2 /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. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in

  6. 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...... in Schizosaccharomyces pombe, and homologs in Caenorhabditis elegans, Xenopus laevis, and Drosophila melanogaster. Defects in three of the RecQ helicases, RecQ4, BLM, and WRN, cause human pathologies linked with cancer predisposition and premature aging. Mutations in the WRN gene are the causative factor of Werner...

  7. The Plant Genome Integrative Explorer Resource: PlantGenIE.org.

    Science.gov (United States)

    Sundell, David; Mannapperuma, Chanaka; Netotea, Sergiu; Delhomme, Nicolas; Lin, Yao-Cheng; Sjödin, Andreas; Van de Peer, Yves; Jansson, Stefan; Hvidsten, Torgeir R; Street, Nathaniel R

    2015-12-01

    Accessing and exploring large-scale genomics data sets remains a significant challenge to researchers without specialist bioinformatics training. We present the integrated PlantGenIE.org platform for exploration of Populus, conifer and Arabidopsis genomics data, which includes expression networks and associated visualization tools. Standard features of a model organism database are provided, including genome browsers, gene list annotation, Blast homology searches and gene information pages. Community annotation updating is supported via integration of WebApollo. We have produced an RNA-sequencing (RNA-Seq) expression atlas for Populus tremula and have integrated these data within the expression tools. An updated version of the ComPlEx resource for performing comparative plant expression analyses of gene coexpression network conservation between species has also been integrated. The PlantGenIE.org platform provides intuitive access to large-scale and genome-wide genomics data from model forest tree species, facilitating both community contributions to annotation improvement and tools supporting use of the included data resources to inform biological insight. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  8. Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

    Science.gov (United States)

    Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

    2013-01-01

    Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

  9. Ethical considerations of research policy for personal genome analysis: the approach of the Genome Science Project in Japan.

    Science.gov (United States)

    Minari, Jusaku; Shirai, Tetsuya; Kato, Kazuto

    2014-12-01

    As evidenced by high-throughput sequencers, genomic technologies have recently undergone radical advances. These technologies enable comprehensive sequencing of personal genomes considerably more efficiently and less expensively than heretofore. These developments present a challenge to the conventional framework of biomedical ethics; under these changing circumstances, each research project has to develop a pragmatic research policy. Based on the experience with a new large-scale project-the Genome Science Project-this article presents a novel approach to conducting a specific policy for personal genome research in the Japanese context. In creating an original informed-consent form template for the project, we present a two-tiered process: making the draft of the template following an analysis of national and international policies; refining the draft template in conjunction with genome project researchers for practical application. Through practical use of the template, we have gained valuable experience in addressing challenges in the ethical review process, such as the importance of sharing details of the latest developments in genomics with members of research ethics committees. We discuss certain limitations of the conventional concept of informed consent and its governance system and suggest the potential of an alternative process using information technology.

  10. A BAC clone fingerprinting approach to the detection of human genome rearrangements

    Science.gov (United States)

    Krzywinski, Martin; Bosdet, Ian; Mathewson, Carrie; Wye, Natasja; Brebner, Jay; Chiu, Readman; Corbett, Richard; Field, Matthew; Lee, Darlene; Pugh, Trevor; Volik, Stas; Siddiqui, Asim; Jones, Steven; Schein, Jacquie; Collins, Collin; Marra, Marco

    2007-01-01

    We present a method, called fingerprint profiling (FPP), that uses restriction digest fingerprints of bacterial artificial chromosome clones to detect and classify rearrangements in the human genome. The approach uses alignment of experimental fingerprint patterns to in silico digests of the sequence assembly and is capable of detecting micro-deletions (1-5 kb) and balanced rearrangements. Our method has compelling potential for use as a whole-genome method for the identification and characterization of human genome rearrangements. PMID:17953769

  11. A Genomic Approach: The Effects of Bisphenol A on Zebrafish

    Science.gov (United States)

    Genomics, proteomics, and metabolomics are emerging technologies used to analyze the effects of the increasing level of environmental pollutants that are affecting aquatic organisms. Some of these toxins are considered endocrine-disrupting chemicals (EDC) due to their interferenc...

  12. An Integrated Computer-Aided Approach for Environmental Studies

    DEFF Research Database (Denmark)

    Gani, Rafiqul; Chen, Fei; Jaksland, Cecilia

    1997-01-01

    A general framework for an integrated computer-aided approach to solve process design, control, and environmental problems simultaneously is presented. Physicochemical properties and their relationships to the molecular structure play an important role in the proposed integrated approach. The sco...... and applicability of the integrated approach is highlighted through examples involving estimation of properties and environmental pollution prevention. The importance of mixture effects on some environmentally important properties is also demonstrated....

  13. Practical Approaches for Detecting Selection in Microbial Genomes

    OpenAIRE

    Hedge, Jessica; Wilson, Daniel J.

    2016-01-01

    Microbial genome evolution is shaped by a variety of selective pressures. Understanding how these processes occur can help to address important problems in microbiology by explaining observed differences in phenotypes, including virulence and resistance to antibiotics. Greater access to whole-genome sequencing provides microbiologists with the opportunity to perform large-scale analyses of selection in novel settings, such as within individual hosts. This tutorial aims to guide researchers th...

  14. CANDU plant life management - An integrated approach

    International Nuclear Information System (INIS)

    Charlebois, P.; Hart, R.S.; Hopkins, J.R.

    1998-01-01

    Commercial versions of CANDU reactors were put into service starting more than 25 years ago. The first unit of Ontario Hydro's Pickering A station was put into service in 1971, and Bruce A in 1977. Most CANDU reactors, however, are only now approaching their mid-life of 15 to 20 years of operation. In particular, the first series of CANDU 6 plants which entered service in the early 1980's were designed for a 30 year life and are now approaching mid life. The current CANDU 6 design is based on a 40 year life as a result of advancement in design and materials through research and development. In order to assure safe and economic operation of these reactors, a comprehensive CANDU Plant Life Management (PLIM) program is being developed from the knowledge gained during the operation of Ontario Hydro's Pickering, Bruce, and Darlington stations, worldwide information from CANDU 6 stations, CANDU research and development programs, and other national and international sources. This integration began its first phase in 1994, with the identification of most of the critical systems structures and components in these stations, and a preliminary assessment of degradation and mechanisms that could affect their fitness for service for their planned life. Most of these preliminary assessments are now complete, together with the production of the first iteration of Life Management Plans for several of the systems and components. The Generic CANDU 6 PLIM program is now reaching its maturity, with formal processes to systematically identify and evaluate the major CSSCs in the station, and a plan to ensure that the plant surveillance, operation, and maintenance programs monitor and control component degradation well within the original design specifications essential for the plant life attainment. A Technology Watch program is being established to ensure that degradation mechanisms which could impact on plant life are promptly investigated and mitigating programs established. The

  15. Global Environmental Change: An integrated modelling approach

    International Nuclear Information System (INIS)

    Den Elzen, M.

    1993-01-01

    Two major global environmental problems are dealt with: climate change and stratospheric ozone depletion (and their mutual interactions), briefly surveyed in part 1. In Part 2 a brief description of the integrated modelling framework IMAGE 1.6 is given. Some specific parts of the model are described in more detail in other Chapters, e.g. the carbon cycle model, the atmospheric chemistry model, the halocarbon model, and the UV-B impact model. In Part 3 an uncertainty analysis of climate change and stratospheric ozone depletion is presented (Chapter 4). Chapter 5 briefly reviews the social and economic uncertainties implied by future greenhouse gas emissions. Chapters 6 and 7 describe a model and sensitivity analysis pertaining to the scientific uncertainties and/or lacunae in the sources and sinks of methane and carbon dioxide, and their biogeochemical feedback processes. Chapter 8 presents an uncertainty and sensitivity analysis of the carbon cycle model, the halocarbon model, and the IMAGE model 1.6 as a whole. Part 4 presents the risk assessment methodology as applied to the problems of climate change and stratospheric ozone depletion more specifically. In Chapter 10, this methodology is used as a means with which to asses current ozone policy and a wide range of halocarbon policies. Chapter 11 presents and evaluates the simulated globally-averaged temperature and sea level rise (indicators) for the IPCC-1990 and 1992 scenarios, concluding with a Low Risk scenario, which would meet the climate targets. Chapter 12 discusses the impact of sea level rise on the frequency of the Dutch coastal defence system (indicator) for the IPCC-1990 scenarios. Chapter 13 presents projections of mortality rates due to stratospheric ozone depletion based on model simulations employing the UV-B chain model for a number of halocarbon policies. Chapter 14 presents an approach for allocating future emissions of CO 2 among regions. (Abstract Truncated)

  16. A management systems approach to pipeline integrity

    Energy Technology Data Exchange (ETDEWEB)

    Abes, J. [CC Technologies Canada, Calgary, AB (Canada)

    2008-07-01

    A management systems approach to pipeline integrity was discussed in terms of accident causation models, lessons from accidents, and management systems. Accident causation models include the Heinrich domino theory; epidemiological models; event chain models; and system-based models. A review of the Bellingham pipeline accident showed that if the pipeline had not been weakened by external damage, it likely would have been able to withstand the pressure that occurred on the day of the rupture, and the accident would not have happened. It was also determined that there was inadequate inspection of excavation work during the water treatment plant project and consequently, there was a failure to identify and repair the damage done to the pipeline. The presentation also addressed other findings, such as inaccurate evaluation of in-line pipeline inspection data; failure to manage and protect the supervisory control and data acquisition system (SCADA); and ineffective management oversight of construction and activation of products terminal. The Carlsbad pipeline explosion was also presented as another example of an accident. Several violations by El Paso were cited, including failure to ensure that qualified personnel performed internal corrosion control procedures; failure to perform necessary tests for corrosion; and failure to follow procedures for continuing surveillance of its facilities. Last, the presentation provided a definition of management systems and discussed the characteristics and elements of a management system. These elements included policy and leadership commitment; organizational structure and responsibilities; management of resources; communication plan; document and records management; operational controls; management of change; and continual improvement. 1 fig.

  17. Integrated NPP life cycle management - Agency's approach

    International Nuclear Information System (INIS)

    Gueorguiev, B.

    2002-01-01

    Full text: The number of nuclear power plants (NPPs) operating in the world has been roughly constant for the past seven years. There are 438 reactors of 353,489 MW(e) capacity in the world and they generated 2448.9 TWh in 2001 giving a total world operating experience with nuclear power of 10,363 years. About 230 units have reached already over 15 years of operation and significant number of these plants are fully depreciated. Share of nuclear power in electricity production sector in Member States utilising nuclear power plants represents a meaningful amount and in 14 countries it exceeds 30%. Therefore, a loss of this share should be covered by new installed capacities either from conventional or alternative sources of electricity generation. Recent forecasts, for nuclear power use over the next two decades range from ∼350 to ∼500 GW(e) worldwide. While assessing the need for any nuclear power related programmes there are several important factors that must be considered since even 350 GW(e) is a very large programme requiring several hundred thousand highly qualified personnel and a substantial infrastructure to assure its continued safe, reliable and cost-effective operation. It is important to assure reliable, safe and economic beneficial performance of the plant, which requires in turn an appropriated management of any activity connected with any taken period of a plant life starting from design and ending by the decided mode of decommissioning. The period between the first and the last payment for the activities connected with the existence of a plant could be defined as a life cycle of the plant. Such integrated approach requires considering the life cycle of the plant in a much broader sense than just operational life and is characterized by the variety of activities and their management represents in a whole a plant life management programme (PLIM). Therefore PLIM could be defined as an aggregate (totality) of technical, financial, economical and

  18. MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics

    Directory of Open Access Journals (Sweden)

    Hardy Nigel

    2006-06-01

    Full Text Available Abstract Background The genome sequencing projects have shown our limited knowledge regarding gene function, e.g. S. cerevisiae has 5–6,000 genes of which nearly 1,000 have an uncertain function. Their gross influence on the behaviour of the cell can be observed using large-scale metabolomic studies. The metabolomic data produced need to be structured and annotated in a machine-usable form to facilitate the exploration of the hidden links between the genes and their functions. Description MeMo is a formal model for representing metabolomic data and the associated metadata. Two predominant platforms (SQL and XML are used to encode the model. MeMo has been implemented as a relational database using a hybrid approach combining the advantages of the two technologies. It represents a practical solution for handling the sheer volume and complexity of the metabolomic data effectively and efficiently. The MeMo model and the associated software are available at http://dbkgroup.org/memo/. Conclusion The maturity of relational database technology is used to support efficient data processing. The scalability and self-descriptiveness of XML are used to simplify the relational schema and facilitate the extensibility of the model necessitated by the creation of new experimental techniques. Special consideration is given to data integration issues as part of the systems biology agenda. MeMo has been physically integrated and cross-linked to related metabolomic and genomic databases. Semantic integration with other relevant databases has been supported through ontological annotation. Compatibility with other data formats is supported by automatic conversion.

  19. RISK INTEGRATION MECHANISMS AND APPROACHES IN BANKING INDUSTRY

    OpenAIRE

    JIANPING LI; JICHUANG FENG; XIAOLEI SUN; MINGLU LI

    2012-01-01

    Recently, the number of consultative documents and research papers that discuss risk integration has grown considerably. This paper presents a comprehensive review of the work done on risk integration in the banking industry. This survey includes: (1) risk integration methods within regulatory frameworks and the banking industry; (2) challenges of risk integration; (3) risk interaction mechanisms; (4) development of risk integration approaches; (5) risk interaction results: diversification ve...

  20. An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

    Science.gov (United States)

    Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

    2017-04-01

    Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Decomposition approaches to integration without a measure

    Czech Academy of Sciences Publication Activity Database

    Greco, S.; Mesiar, Radko; Rindone, F.; Sipeky, L.

    2016-01-01

    Roč. 287, č. 1 (2016), s. 37-47 ISSN 0165-0114 Institutional support: RVO:67985556 Keywords : Choquet integral * Decision making * Decomposition integral Subject RIV: BA - General Mathematics Impact factor: 2.718, year: 2016 http://library.utia.cas.cz/separaty/2016/E/mesiar-0457408.pdf

  2. Integrated, multi-scale, spatial-temporal cell biology--A next step in the post genomic era.

    Science.gov (United States)

    Horwitz, Rick

    2016-03-01

    New microscopic approaches, high-throughput imaging, and gene editing promise major new insights into cellular behaviors. When coupled with genomic and other 'omic information and "mined" for correlations and associations, a new breed of powerful and useful cellular models should emerge. These top down, coarse-grained, and statistical models, in turn, can be used to form hypotheses merging with fine-grained, bottom up mechanistic studies and models that are the back bone of cell biology. The goal of the Allen Institute for Cell Science is to develop the top down approach by developing a high throughput microscopy pipeline that is integrated with modeling, using gene edited hiPS cell lines in various physiological and pathological contexts. The output of these experiments and models will be an "animated" cell, capable of integrating and analyzing image data generated from experiments and models. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. Prolonged Integration Site Selection of a Lentiviral Vector in the Genome of Human Keratinocytes.

    Science.gov (United States)

    Qian, Wei; Wang, Yong; Li, Rui-Fu; Zhou, Xin; Liu, Jing; Peng, Dai-Zhi

    2017-03-03

    BACKGROUND Lentiviral vectors have been successfully used for human skin cell gene transfer studies. Defining the selection of integration sites for retroviral vectors in the host genome is crucial in risk assessment analysis of gene therapy. However, genome-wide analyses of lentiviral integration sites in human keratinocytes, especially after prolonged growth, are poorly understood. MATERIAL AND METHODS In this study, 874 unique lentiviral vector integration sites in human HaCaT keratinocytes after long-term culture were identified and analyzed with the online tool GTSG-QuickMap and SPSS software. RESULTS The data indicated that lentiviral vectors showed integration site preferences for genes and gene-rich regions. CONCLUSIONS This study will likely assist in determining the relative risks of the lentiviral vector system and in the design of a safe lentiviral vector system in the gene therapy of skin diseases.

  6. Genetic counselors' views and experiences with the clinical integration of genome sequencing.

    Science.gov (United States)

    Machini, Kalotina; Douglas, Jessica; Braxton, Alicia; Tsipis, Judith; Kramer, Kate

    2014-08-01

    In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors- one third of whom currently offer WES/WGS-participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counseling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of

  7. Predicting co-complexed protein pairs using genomic and proteomic data integration

    Directory of Open Access Journals (Sweden)

    King Oliver D

    2004-04-01

    Full Text Available Abstract Background Identifying all protein-protein interactions in an organism is a major objective of proteomics. A related goal is to know which protein pairs are present in the same protein complex. High-throughput methods such as yeast two-hybrid (Y2H and affinity purification coupled with mass spectrometry (APMS have been used to detect interacting proteins on a genomic scale. However, both Y2H and APMS methods have substantial false-positive rates. Aside from high-throughput interaction screens, other gene- or protein-pair characteristics may also be informative of physical interaction. Therefore it is desirable to integrate multiple datasets and utilize their different predictive value for more accurate prediction of co-complexed relationship. Results Using a supervised machine learning approach – probabilistic decision tree, we integrated high-throughput protein interaction datasets and other gene- and protein-pair characteristics to predict co-complexed pairs (CCP of proteins. Our predictions proved more sensitive and specific than predictions based on Y2H or APMS methods alone or in combination. Among the top predictions not annotated as CCPs in our reference set (obtained from the MIPS complex catalogue, a significant fraction was found to physically interact according to a separate database (YPD, Yeast Proteome Database, and the remaining predictions may potentially represent unknown CCPs. Conclusions We demonstrated that the probabilistic decision tree approach can be successfully used to predict co-complexed protein (CCP pairs from other characteristics. Our top-scoring CCP predictions provide testable hypotheses for experimental validation.

  8. An integrated approach to change leadership.

    Science.gov (United States)

    Skelton-Green, Judith; Simpson, Beverley; Scott, Julia

    2007-01-01

    Leading change has become one of the essential core competencies of health professionals today. Since 2001, the authors have been the key designers and facilitators of the Dorothy Wylie Nursing Leadership Institute (DMW-NLI). The background, key characteristics and benefits of the DMW-NLI have been described in detail elsewhere (Simpson et al. 2002). One of the Institute's key features is that participants bring a change initiative that they wish to pursue and - during their time on site - we assist them in developing that project to the point where it has a strong chance of success. When we incorporated this aspect into the DMW-NLI program, we believed that opportunity to apply the learning of the Institute to a desired initiative in the home setting would add significant value, not only to the participants, but also to their sponsoring organizations. Further, it was our hope that we could develop a methodology to advance the change initiative, which would be a valuable tool that participants could use in future change projects.As we looked to the literature, we found no shortage of articles on change theory, as well as numerous tools and techniques for project management. However, we did not find one single approach or methodology that we felt was comprehensive yet concise enough to serve as a practical guide for those who wish to advance a change initiative in their practice settings today. Therefore, we developed an integrated conceptual framework and methodology for leading change initiatives, building on selected current and classic theories of change that are relevant today. Both the framework and methodology have proven very hardy, and will, we believe, be of interest to nurse leaders and other health professionals in leadership roles. This paper will provide a brief overview of relevant background literature on leading change initiatives, introduce the DMW-NLI Change Leadership conceptual framework, describe a number of activities that support the

  9. An Alternative Methodological Approach for Cost-Effectiveness Analysis and Decision Making in Genomic Medicine.

    Science.gov (United States)

    Fragoulakis, Vasilios; Mitropoulou, Christina; van Schaik, Ron H; Maniadakis, Nikolaos; Patrinos, George P

    2016-05-01

    Genomic Medicine aims to improve therapeutic interventions and diagnostics, the quality of life of patients, but also to rationalize healthcare costs. To reach this goal, careful assessment and identification of evidence gaps for public health genomics priorities are required so that a more efficient healthcare environment is created. Here, we propose a public health genomics-driven approach to adjust the classical healthcare decision making process with an alternative methodological approach of cost-effectiveness analysis, which is particularly helpful for genomic medicine interventions. By combining classical cost-effectiveness analysis with budget constraints, social preferences, and patient ethics, we demonstrate the application of this model, the Genome Economics Model (GEM), based on a previously reported genome-guided intervention from a developing country environment. The model and the attendant rationale provide a practical guide by which all major healthcare stakeholders could ensure the sustainability of funding for genome-guided interventions, their adoption and coverage by health insurance funds, and prioritization of Genomic Medicine research, development, and innovation, given the restriction of budgets, particularly in developing countries and low-income healthcare settings in developed countries. The implications of the GEM for the policy makers interested in Genomic Medicine and new health technology and innovation assessment are also discussed.

  10. Data Integration The Relational Logic Approach

    CERN Document Server

    Genesereth, Michael

    2010-01-01

    Data integration is a critical problem in our increasingly interconnected but inevitably heterogeneous world. There are numerous data sources available in organizational databases and on public information systems like the World Wide Web. Not surprisingly, the sources often use different vocabularies and different data structures, being created, as they are, by different people, at different times, for different purposes. The goal of data integration is to provide programmatic and human users with integrated access to multiple, heterogeneous data sources, giving each user the illusion of a sin

  11. Whole-genome-based Mycobacterium tuberculosis surveillance: a standardized, portable, and expandable approach.

    Science.gov (United States)

    Kohl, Thomas A; Diel, Roland; Harmsen, Dag; Rothgänger, Jörg; Walter, Karen Meywald; Merker, Matthias; Weniger, Thomas; Niemann, Stefan

    2014-07-01

    Whole-genome sequencing (WGS) allows for effective tracing of Mycobacterium tuberculosis complex (MTBC) (tuberculosis pathogens) transmission. However, it is difficult to standardize and, therefore, is not yet employed for interlaboratory prospective surveillance. To allow its widespread application, solutions for data standardization and storage in an easily expandable database are urgently needed. To address this question, we developed a core genome multilocus sequence typing (cgMLST) scheme for clinical MTBC isolates using the Ridom SeqSphere(+) software, which transfers the genome-wide single nucleotide polymorphism (SNP) diversity into an allele numbering system that is standardized, portable, and not computationally intensive. To test its performance, we performed WGS analysis of 26 isolates with identical IS6110 DNA fingerprints and spoligotyping patterns from a longitudinal outbreak in the federal state of Hamburg, Germany (notified between 2001 and 2010). The cgMLST approach (3,041 genes) discriminated the 26 strains with a resolution comparable to that of SNP-based WGS typing (one major cluster of 22 identical or closely related and four outlier isolates with at least 97 distinct SNPs or 63 allelic variants). Resulting tree topologies are highly congruent and grouped the isolates in both cases analogously. Our data show that SNP- and cgMLST-based WGS analyses facilitate high-resolution discrimination of longitudinal MTBC outbreaks. cgMLST allows for a meaningful epidemiological interpretation of the WGS genotyping data. It enables standardized WGS genotyping for epidemiological investigations, e.g., on the regional public health office level, and the creation of web-accessible databases for global TB surveillance with an integrated early warning system. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. IW-Scoring: an Integrative Weighted Scoring framework for annotating and prioritizing genetic variations in the noncoding genome.

    Science.gov (United States)

    Wang, Jun; Dayem Ullah, Abu Z; Chelala, Claude

    2018-01-30

    The vast majority of germline and somatic variations occur in the noncoding part of the genome, only a small fraction of which are believed to be functional. From the tens of thousands of noncoding variations detectable in each genome, identifying and prioritizing driver candidates with putative functional significance is challenging. To address this, we implemented IW-Scoring, a new Integrative Weighted Scoring model to annotate and prioritise functionally relevant noncoding variations. We evaluate 11 scoring methods, and apply an unsupervised spectral approach for subsequent selective integration into two linear weighted functional scoring schemas for known and novel variations. IW-Scoring produces stable high-quality performance as the best predictors for three independent data sets. We demonstrate the robustness of IW-Scoring in identifying recurrent functional mutations in the TERT promoter, as well as disease SNPs in proximity to consensus motifs and with gene regulatory effects. Using follicular lymphoma as a paradigmatic cancer model, we apply IW-Scoring to locate 11 recurrently mutated noncoding regions in 14 follicular lymphoma genomes, and validate 9 of these regions in an extension cohort, including the promoter and enhancer regions of PAX5. Overall, IW-Scoring demonstrates greater versatility in identifying trait- and disease-associated noncoding variants. Scores from IW-Scoring as well as other methods are freely available from http://www.snp-nexus.org/IW-Scoring/. © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. A genome-wide approach to children's aggressive behavior: The EAGLE consortium

    NARCIS (Netherlands)

    Pappa, I.; St Pourcain, B.; Benke, K.S.; Cavadino, A.; Hakulinen, C.; Nivard, M.G.; Nolte, I.M.; Tiesler, C.M.T.; Bakermans-Kranenburg, M.J.; Davies, G.E.; Evans, D.M.; Geoffroy, M.C.; Grallert, H.; Blokhuis, M.M.; Hudziak, J.J.; Kemp, J.P.; Keltikangas-Järvinen, L.; McMahon, G.; Mileva-Seitz, V.R.; Motazedi, E.; Power, C.; Raitakari, O.T.; Ring, S.M.; Rivadeneira, F.; Rodriguez, A.; Scheet, P.; Seppälä, I.; Snieder, H.; Standl, M.; Thiering, E.; Timpson, N.J.; Veenstra, R.; Velders, F.P.; Whitehouse, A.J.O.; Davey Smith, G.; Heinrich, J.; Hypponen, E.; Lehtimäki, T.; Middeldorp, C.M.; Oldehinkel, A.J.; Pennell, C.E.; Boomsma, D.I.; Tiemeier, H.

    2016-01-01

    Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of

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

    DEFF Research Database (Denmark)

    King, Zachary A.; Lu, Justin; Dräger, Andreas

    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 repo...

  15. 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

  16. Filling the knowledge gap: Integrating quantitative genetics and genomics in graduate education and outreach

    Science.gov (United States)

    The genomics revolution provides vital tools to address global food security. Yet to be incorporated into livestock breeding, molecular techniques need to be integrated into a quantitative genetics framework. Within the U.S., with shrinking faculty numbers with the requisite skills, the capacity to ...

  17. Quantitative and Qualitative Proteome Characteristics Extracted from In-Depth Integrated Genomics and Proteomics Analysis

    NARCIS (Netherlands)

    Low, Teck Yew; van Heesch, Sebastiaan; van den Toorn, Henk; Giansanti, Piero; Cristobal, Alba; Toonen, Pim; Schafer, Sebastian; Huebner, Norbert; van Breukelen, Bas; Mohammed, Shabaz; Cuppen, Edwin; Heck, Albert J. R.; Guryev, Victor

    2013-01-01

    Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and post-transcriptional 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

  18. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahep...

  19. Nucleotide excision repair : a multi-step mechanism required to maintain genome integrity

    NARCIS (Netherlands)

    Moser, Jill

    2010-01-01

    DNA is continuously exposed to exogenous and genotoxic insults including ionizing and ultraviolet radiation as well as chemical agents. DNA damage can compromise the integrity of the genome and have potentially deleterious effects. Ultraviolet light (UV) can induce the formation of helix distorting

  20. Practical Approaches for Detecting Selection in Microbial Genomes.

    Directory of Open Access Journals (Sweden)

    Jessica Hedge

    2016-02-01

    Full Text Available Microbial genome evolution is shaped by a variety of selective pressures. Understanding how these processes occur can help to address important problems in microbiology by explaining observed differences in phenotypes, including virulence and resistance to antibiotics. Greater access to whole-genome sequencing provides microbiologists with the opportunity to perform large-scale analyses of selection in novel settings, such as within individual hosts. This tutorial aims to guide researchers through the fundamentals underpinning popular methods for measuring selection in pathogens. These methods are transferable to a wide variety of organisms, and the exercises provided are designed for researchers with any level of programming experience.

  1. Practical Approaches for Detecting Selection in Microbial Genomes.

    Science.gov (United States)

    Hedge, Jessica; Wilson, Daniel J

    2016-02-01

    Microbial genome evolution is shaped by a variety of selective pressures. Understanding how these processes occur can help to address important problems in microbiology by explaining observed differences in phenotypes, including virulence and resistance to antibiotics. Greater access to whole-genome sequencing provides microbiologists with the opportunity to perform large-scale analyses of selection in novel settings, such as within individual hosts. This tutorial aims to guide researchers through the fundamentals underpinning popular methods for measuring selection in pathogens. These methods are transferable to a wide variety of organisms, and the exercises provided are designed for researchers with any level of programming experience.

  2. Polymer reaction engineering, an integrated approach

    NARCIS (Netherlands)

    Meyer, T.; Keurentjes, J.T.F.; Meyer, T.; Keurentjes, J.T.F.

    2005-01-01

    Summary This chapter contains sections titled: Polymer Materials A Short History of Polymer Reaction Engineering The Position of Polymer Reaction Engineering Toward Integrated Polymer Reaction Engineering The Disciplines in Polymer Reaction Engineering The Future: Product-inspired Polymer Reaction

  3. The role of duplications in the evolution of genomes highlights the need for evolutionary-based approaches in comparative genomics

    Directory of Open Access Journals (Sweden)

    Levasseur Anthony

    2011-02-01

    Full Text Available Abstract Understanding the evolutionary plasticity of the genome requires a global, comparative approach in which genetic events are considered both in a phylogenetic framework and with regard to population genetics and environmental variables. In the mechanisms that generate adaptive and non-adaptive changes in genomes, segmental duplications (duplication of individual genes or genomic regions and polyploidization (whole genome duplications are well-known driving forces. The probability of fixation and maintenance of duplicates depends on many variables, including population sizes and selection regimes experienced by the corresponding genes: a combination of stochastic and adaptive mechanisms has shaped all genomes. A survey of experimental work shows that the distinction made between fixation and maintenance of duplicates still needs to be conceptualized and mathematically modeled. Here we review the mechanisms that increase or decrease the probability of fixation or maintenance of duplicated genes, and examine the outcome of these events on the adaptation of the organisms. Reviewers This article was reviewed by Dr. Etienne Joly, Dr. Lutz Walter and Dr. W. Ford Doolittle.

  4. AIM: An Integrated Approach to Organizational Improvement

    Directory of Open Access Journals (Sweden)

    Ronald A. Styron, Jr.

    2016-02-01

    Full Text Available This concept paper is based on the new problem-solving model of Blended Leadership called Alloy Improvement Model (AIM. This model consists of an integration of change theory, leadership theory, and democratic principles and practices to form a comprehensive problem-solving strategy for organizational leaders. The utilization of AIM will assist leaders in moving from problems to solutions while engaging stakeholders in a comprehensive, efficient, inclusive, informative, integrated and transparent process.

  5. Integrated crop protection as a system approach

    OpenAIRE

    Haan, de, J.J.; Wijnands, F.G.; Sukkel, W.

    2005-01-01

    New farming systems in vegetable production are required as demands for high quality products that do not pollute the environment are rising, and production risks are large and incomes low. The methodology of prototyping new systems is described, especially the themes, parameters and target values connected to integrated crop protection. The role of integrated crop protection in prototyping new systems is discussed. The results of twenty years working with this prototyping methodology are pre...

  6. Integrative approaches to the prediction of protein functions based on the feature selection

    Directory of Open Access Journals (Sweden)

    Lee Hyunju

    2009-12-01

    Full Text Available Abstract Background Protein function prediction has been one of the most important issues in functional genomics. With the current availability of various genomic data sets, many researchers have attempted to develop integration models that combine all available genomic data for protein function prediction. These efforts have resulted in the improvement of prediction quality and the extension of prediction coverage. However, it has also been observed that integrating more data sources does not always increase the prediction quality. Therefore, selecting data sources that highly contribute to the protein function prediction has become an important issue. Results We present systematic feature selection methods that assess the contribution of genome-wide data sets to predict protein functions and then investigate the relationship between genomic data sources and protein functions. In this study, we use ten different genomic data sources in Mus musculus, including: protein-domains, protein-protein interactions, gene expressions, phenotype ontology, phylogenetic profiles and disease data sources to predict protein functions that are labelled with Gene Ontology (GO terms. We then apply two approaches to feature selection: exhaustive search feature selection using a kernel based logistic regression (KLR, and a kernel based L1-norm regularized logistic regression (KL1LR. In the first approach, we exhaustively measure the contribution of each data set for each function based on its prediction quality. In the second approach, we use the estimated coefficients of features as measures of contribution of data sources. Our results show that the proposed methods improve the prediction quality compared to the full integration of all data sources and other filter-based feature selection methods. We also show that contributing data sources can differ depending on the protein function. Furthermore, we observe that highly contributing data sets can be similar among

  7. The Impact of Technology Integration through a Transformative Approach

    Science.gov (United States)

    Cubillos, Jo Ann

    2013-01-01

    The integration of technology into classroom instruction in K-12 schools remains problematic. The problems associated with this integration are troubling, as technology integration may change a teacher's pedagogy toward more innovative approaches that increase student achievement. The purpose of this study was to document teachers' experiences as…

  8. Integrating Adult Learning and Technologies for Effective Education: Strategic Approaches

    Science.gov (United States)

    Wang, Victor C. X.

    2010-01-01

    As adult learners and educators pioneer the use of technology in the new century, attention has been focused on developing strategic approaches to effectively integrate adult learning and technology in different learning environments. "Integrating Adult Learning and Technologies for Effective Education: Strategic Approaches" provides innovative…

  9. HeartMath and Ubuntu integral healing approaches for social ...

    African Journals Online (AJOL)

    HeartMath and Ubuntu integral healing approaches for social coherence and physical activity. Stephen D. Edwards. Abstract. This research was motivated by many social health problems confronting planet earth. Its aim is to introduce HeartMath and Ubuntu as complimentary, integral healing approaches for promoting ...

  10. The Intersystem Model of Psychotherapy: An Integrated Systems Treatment Approach

    Science.gov (United States)

    Weeks, Gerald R.; Cross, Chad L.

    2004-01-01

    This article introduces the intersystem model of psychotherapy and discusses its utility as a truly integrative and comprehensive approach. The foundation of this conceptually complex approach comes from dialectic metatheory; hence, its derivation requires an understanding of both foundational and integrational constructs. The article provides a…

  11. 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

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

    Science.gov (United States)

    Belyi, Vladimir A; Levine, Arnold J; Skalka, Anna Marie

    2010-07-29

    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 biological

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

    Directory of Open Access Journals (Sweden)

    Vladimir A Belyi

    2010-07-01

    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

  14. An Assessment of Different Genomic Approaches for Inferring Phylogeny of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Clémentine Henri

    2017-11-01

    Full Text Available Background/objectives: Whole genome sequencing (WGS has proven to be a powerful subtyping tool for foodborne pathogenic bacteria like L. monocytogenes. The interests of genome-scale analysis for national surveillance, outbreak detection or source tracking has been largely documented. The genomic data however can be exploited with many different bioinformatics methods like single nucleotide polymorphism (SNP, core-genome multi locus sequence typing (cgMLST, whole-genome multi locus sequence typing (wgMLST or multi locus predicted protein sequence typing (MLPPST on either core-genome (cgMLPPST or pan-genome (wgMLPPST. Currently, there are little comparisons studies of these different analytical approaches. Our objective was to assess and compare different genomic methods that can be implemented in order to cluster isolates of L. monocytogenes.Methods: The clustering methods were evaluated on a collection of 207 L. monocytogenes genomes of food origin representative of the genetic diversity of the Anses collection. The trees were then compared using robust statistical analyses.Results: The backward comparability between conventional typing methods and genomic methods revealed a near-perfect concordance. The importance of selecting a proper reference when calling SNPs was highlighted, although distances between strains remained identical. The analysis also revealed that the topology of the phylogenetic trees between wgMLST and cgMLST were remarkably similar. The comparison between SNP and cgMLST or SNP and wgMLST approaches showed that the topologies of phylogenic trees were statistically similar with an almost equivalent clustering.Conclusion: Our study revealed high concordance between wgMLST, cgMLST, and SNP approaches which are all suitable for typing of L. monocytogenes. The comparable clustering is an important observation considering that the two approaches have been variously implemented among reference laboratories.

  15. Investigation of Integrated Vehicle Health Management Approaches

    Science.gov (United States)

    Paris, Deidre

    2005-01-01

    This report is to present the work that was performed during the summer in the Advance Computing Application office. The NFFP (NASA Faculty Fellow Program) had ten summer faculty members working on IVHM (Integrated Vehicle Health Management) technologies. The objective of this project was two-fold: 1) to become familiar with IVHM concepts and key demonstrated IVHM technologies; and 2) to integrate the research that has been performed by IVHM faculty members into the MASTLAB (Marshall Avionic Software Test Lab). IVHM is a NASA-wide effort to coordinate, integrate and apply advanced software, sensors and design technologies to increase the level of intelligence, autonomy, and health state of future vehicles. IVHM is an important concept because it is consistent with the current plan for NASA to go to the moon, mars, and beyond. In order for NASA to become more involved in deep exploration, avionic systems will need to be highly adaptable and autonomous.

  16. 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.

  17. 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.

  18. A chromosomal genomics approach to assess and validate the desi and kabuli draft chickpea genome assemblies

    Czech Academy of Sciences Publication Activity Database

    Ruperao, P.; Chan, C.K.K.; Azam, S.; Karafiátová, Miroslava; Hayashi, S.; Čížková, Jana; Šimková, Hana; Vrána, Jan; Doležel, Jaroslav; Varshney, R.K.; Edwards, D.

    2014-01-01

    Roč. 12, č. 6 (2014), s. 778-786 ISSN 1467-7644 R&D Projects: GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : chickpea * genome assembly * cytogenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.752, year: 2014

  19. 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.

  20. Integrative Genomics: Quantifying significance of phenotype-genotype relationships from multiple sources of high-throughput data

    Directory of Open Access Journals (Sweden)

    Eric eGamazon

    2013-05-01

    Full Text Available Given recent advances in the generation of high-throughput data such as whole genome genetic variation and transcriptome expression, it is critical to come up with novel methods to integrate these heterogeneous datasets and to assess the significance of identified phenotype-genotype relationships. Recent studies show that genome-wide association findings are likely to fall in loci with gene regulatory effects such as expression quantitative trait loci (eQTLs, demonstrating the utility of such integrative approaches. When genotype and gene expression data are available on the same individuals, we developed methods wherein top phenotype-associated genetic variants are prioritized if they are associated, as eQTLs, with gene expression traits that are themselves associated with the phenotype. Yet there has been no method to determine an overall p-value for the findings that arise specifically from the integrative nature of the approach. We propose a computationally feasible permutation method that accounts for the assimilative nature of the method and the correlation structure among gene expression traits and among genotypes. We apply the method to data from a study of cellular sensitivity to etoposide, one of the most widely used chemotherapeutic drugs. To our knowledge, this study is the first statistically sound quantification of the significance of the genotype-phenotype relationships resulting from applying an integrative approach. This method can be easily extended to cases in which gene expression data are replaced by other molecular phenotypes of interest, e.g., microRNA or proteomic data. This study has important implications for studies seeking to expand on genetic association studies by the use of omics data. Finally, we provide an R code to compute the empirical FDR when p-values for the observed and simulated phenotypes are available.

  1. THE FEMINIST APPROACH TO PSYCHOTHERAPY INTEGRATION

    OpenAIRE

    Lorena Božac Deležan

    2011-01-01

    The goal of Integrative Psychotherapy is to establish full inner and external contact (Moursund & Erskine, 2004). The most important goal in feminist therapy is the transformation of an individual as well as the transformation of the society as a whole (Herlihy & Corey, 2004). In my work I attempt to integrate both: to help the client establish inner and external contact, but also help him/her to become aware and recognize inner messages connected with his/her gender and replace them with con...

  2. Design of Integrated Circuits Approaching Terahertz Frequencies

    DEFF Research Database (Denmark)

    Yan, Lei

    In this thesis, monolithic microwave integrated circuits(MMICs) are presented for millimeter-wave and submillimeter-wave or terahertz(THz) applications. Millimeter-wave power generation from solid state devices is not only crucial for the emerging high data rate wireless communications but also...... heterodyne receivers with requirements of room temperature operation, low system complexity, and high sensitivity, monolithic integrated Schottky diode technology is chosen for the implementation of submillimeterwave components. The corresponding subharmonic mixer and multiplier for a THz radiometer system...

  3. Approaches to Integrated Building Design Environments

    DEFF Research Database (Denmark)

    Bagger-Petersen, Susanne C; Andersen, Tom

    1996-01-01

    This report discusses functional requirements and specification which needs to be defined and fulfilled to initiate development of an integrated building design environment. The purpose is to outline specifications for further discussion and development. The report documents the first phase...... in an ongoing project at the Technical University of Denmark. The overall project objective is to provide a theoretically well-founded prototype of an integrated IT-system which can serve as a device of feedback from practice and as a test-bed for the developed concept and architecture....

  4. Field theory a path integral approach

    CERN Document Server

    Das, Ashok

    2006-01-01

    This unique book describes quantum field theory completely within the context of path integrals. With its utility in a variety of fields in physics, the subject matter is primarily developed within the context of quantum mechanics before going into specialized areas.Adding new material keenly requested by readers, this second edition is an important expansion of the popular first edition. Two extra chapters cover path integral quantization of gauge theories and anomalies, and a new section extends the supersymmetry chapter, where singular potentials in supersymmetric systems are described.

  5. An integrated clinical and genomic information system for cancer precision medicine.

    Science.gov (United States)

    Jang, Yeongjun; Choi, Taekjin; Kim, Jongho; Park, Jisub; Seo, Jihae; Kim, Sangok; Kwon, Yeajee; Lee, Seungjae; Lee, Sanghyuk

    2018-04-20

    Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex nature of genomic information presents a huge challenge for clinicians in interpreting the patient's genomic alterations and selecting the optimum approved or investigational therapy. An elaborate and practical information system is urgently needed to support clinical decision as well as to test clinical hypotheses quickly. Here, we present an integrated clinical and genomic information system (CGIS) based on NGS data analyses. Major components include modules for handling clinical data, NGS data processing, variant annotation and prioritization, drug-target-pathway analysis, and population cohort explorer. We built a comprehensive knowledgebase of genes, variants, drugs by collecting annotated information from public and in-house resources. Structured reports for molecular pathology are generated using standardized terminology in order to help clinicians interpret genomic variants and utilize them for targeted cancer therapy. We also implemented many features useful for testing hypotheses to develop prognostic markers from mutation and gene expression data. Our CGIS software is an attempt to provide useful information for both clinicians and scientists who want to explore genomic information for precision oncology.

  6. Development of Multisensory Integration Approach Model

    Science.gov (United States)

    Kumar, S. Prasanna; Nathan, B. Sami

    2016-01-01

    Every teacher expects optimum level of processing in mind of them students. The level of processing is mainly depends upon memory process. Most of the students have retrieval difficulties on past learning. Memory difficulties directly related to sensory integration. In these circumstances the investigator made an attempt to construct Multisensory…

  7. The Integration Movement in the Caribbean at Crossroads: Towards a New Approach of Integration

    OpenAIRE

    Uziel Nogueira

    1997-01-01

    The Institute for the Integration of Latin America and the Caribbean (INTAL) has inaugurated a Working Papers Series with the publication of a study by Uziel Nogueira, the Institute's Economist. Entitled "The Integration Movement in the Caribbean at the Crossroads: Towards a New Approach to Integration", the study opens with an overview of the movement towards integration among the English-speaking countries of the Caribbean. It continues with an analysis of the integration process during thi...

  8. 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.

  9. An integrative approach to apprehend desistance.

    Science.gov (United States)

    F-Dufour, Isabelle; Brassard, Renée; Martel, Joane

    2015-05-01

    The process underlying desistance is still a strong subject of debate. This article seeks to introduce several core concepts of Archer's morphogenic approach to study how people desist from crime. At first, it discusses the primary existing theories of desistance. Then, this article demonstrates the usefulness of this approach by presenting empirical evidence drawn from semistructured interviews collected with 29 men who desisted from crime in an eastern province of Canada. The study demonstrates how this alternative approach allows for the consolidation of existing knowledge on desistance. Then implication of these findings for both theory and practice are discussed. © The Author(s) 2013.

  10. A hybrid reference-guided de novo assembly approach for generating Cyclospora mitochondrion genomes.

    Science.gov (United States)

    Gopinath, G R; Cinar, H N; Murphy, H R; Durigan, M; Almeria, M; Tall, B D; DaSilva, A J

    2018-01-01

    Cyclospora cayetanensis is a coccidian parasite associated with large and complex foodborne outbreaks worldwide. Linking samples from cyclosporiasis patients during foodborne outbreaks with suspected contaminated food sources, using conventional epidemiological methods, has been a persistent challenge. To address this issue, development of new methods based on potential genomically-derived markers for strain-level identification has been a priority for the food safety research community. The absence of reference genomes to identify nucleotide and structural variants with a high degree of confidence has limited the application of using sequencing data for source tracking during outbreak investigations. In this work, we determined the quality of a high resolution, curated, public mitochondrial genome assembly to be used as a reference genome by applying bioinformatic analyses. Using this reference genome, three new mitochondrial genome assemblies were built starting with metagenomic reads generated by sequencing DNA extracted from oocysts present in stool samples from cyclosporiasis patients. Nucleotide variants were identified in the new and other publicly available genomes in comparison with the mitochondrial reference genome. A consolidated workflow, presented here, to generate new mitochondrion genomes using our reference-guided de novo assembly approach could be useful in facilitating the generation of other mitochondrion sequences, and in their application for subtyping C. cayetanensis strains during foodborne outbreak investigations.

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

    Science.gov (United States)

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

    2015-10-14

    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. An average of 75.22 ± 9.52 integration sites per bird were identified, which collectively group into 279 intervals of which 5 % are common to 90 % of the genomes analysed and are suggestive of pre-domestication integration events. More than a third of intervals are specific to individual genomes, supporting active circulation of EAV-HP in modern chickens. Interval density is correlated with chromosome length (P < 2.31(-6)), and 27 % of intervals are located within 5 kb of a transcript. Functional annotation clustering of genes reveals enrichment for immune-related functions (P < 0.05). Our results illustrate a non-random distribution of EAV-HP in the genome, emphasising the importance it may have played in the adaptation of the species, and provide a platform from which to extend investigations on the co-evolutionary significance of endogenous retroviral genera with their hosts.

  12. Rabbit models for biomedical research revisited via genome editing approaches

    Science.gov (United States)

    HONDA, Arata; OGURA, Atsuo

    2017-01-01

    Although the laboratory rabbit has long contributed to many paradigmatic studies in biology and medicine, it is often considered to be a “classical animal model” because in the last 30 years, the laboratory mouse has been more often used, thanks to the availability of embryonic stem cells that have allowed the generation of gene knockout (KO) animals. However, recent genome-editing strategies have changed this unrivaled condition; so far, more than 10 mammalian species have been added to the list of KO animals. Among them, the rabbit has distinct advantages for application of genome-editing systems, such as easy application of superovulation, consistency with fertile natural mating, well-optimized embryo manipulation techniques, and the short gestation period. The rabbit has now returned to the stage of advanced biomedical research. PMID:28579598

  13. Integrated approach to economical, reliable, safe nuclear power production

    International Nuclear Information System (INIS)

    1982-06-01

    An Integrated Approach to Economical, Reliable, Safe Nuclear Power Production is the latest evolution of a concept which originated with the Defense-in-Depth philosophy of the nuclear industry. As Defense-in-Depth provided a framework for viewing physical barriers and equipment redundancy, the Integrated Approach gives a framework for viewing nuclear power production in terms of functions and institutions. In the Integrated Approach, four plant Goals are defined (Normal Operation, Core and Plant Protection, Containment Integrity and Emergency Preparedness) with the attendant Functional and Institutional Classifications that support them. The Integrated Approach provides a systematic perspective that combines the economic objective of reliable power production with the safety objective of consistent, controlled plant operation

  14. Rabbit models for biomedical research revisited via genome editing approaches

    OpenAIRE

    HONDA, Arata; OGURA, Atsuo

    2017-01-01

    Although the laboratory rabbit has long contributed to many paradigmatic studies in biology and medicine, it is often considered to be a “classical animal model” because in the last 30 years, the laboratory mouse has been more often used, thanks to the availability of embryonic stem cells that have allowed the generation of gene knockout (KO) animals. However, recent genome-editing strategies have changed this unrivaled condition; so far, more than 10 mammalian species have been added to the ...

  15. Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Kusko, Rebecca L; Brothers, John F; Tedrow, John; Pandit, Kusum; Huleihel, Luai; Perdomo, Catalina; Liu, Gang; Juan-Guardela, Brenda; Kass, Daniel; Zhang, Sherry; Lenburg, Marc; Martinez, Fernando; Quackenbush, John; Sciurba, Frank; Limper, Andrew; Geraci, Mark; Yang, Ivana; Schwartz, David A; Beane, Jennifer; Spira, Avrum; Kaminski, Naftali

    2016-10-15

    Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

  16. Design of Integrated Circuits Approaching Terahertz Frequencies

    OpenAIRE

    Yan, Lei; Johansen, Tom Keinicke

    2013-01-01

    In this thesis, monolithic microwave integrated circuits(MMICs) are presented for millimeter-wave and submillimeter-wave or terahertz(THz) applications. Millimeter-wave power generation from solid state devices is not only crucial for the emerging high data rate wireless communications but also important for driving THz signal sources. To meet the requirement of high output power, amplifiers based on InP double heterojunction bipolar transistor (DHBT) devices from the III-V Lab in Marcoussic,...

  17. Virtual integration: A game-theoretic approach

    OpenAIRE

    Schorer, Michael

    2014-01-01

    Embedded systems are playing a key role to enable the features of todays cars and other road vehicles. Advances in current hardware platforms of these embedded systems and growing implementation of features in software rather than in new hardware modules lead to new and continuously more complex automotive software systems. The integration process in the course of development of automotive software systems is a crucial and complex phase. An efficient combination of the set of components i...

  18. Concept for integrated environmental monitoring. Scientific approach

    Energy Technology Data Exchange (ETDEWEB)

    Haber, W [comp.; Schoenthaler, K; Kerner, H F; Koeppel, J; Spandau, L

    1998-09-01

    Despite considerable expenditures for environmental protection and intensified efforts in the areas of environmental research and monitoring, environmental damage increasingly occurs, sometimes with global effects, largely due to the lack of early diagnosis. In the past few years various institutions have therefore demanded improvements in environmental monitoring. The Council of Experts on Environmental Issues (`Rat von Sachverstaendigen fuer Umweltfragen`, SRU), in particular, in its `Environmental Report` of 1987 and in its Special Report on `General Ecological Environmental Monitoring` (1990) presented far-reaching demands for a nationwide ecological early warning system which should integrate the various local, regional, national, and even global monitoring levels, and which should encompass an environmental monitoring of entire ecosystems at representative locations. This is aimed at creating the prerequisites for - detection of long-term gradual environmental change, - confirmation of refutation of initial assumptions regarding the causes of these environmental changes, - permitting decisions on preventive actions to stabilize or improve environmental conditions and - making it possible to assess the success of environmental protection policies. This report includes an abbreviated version and documentation of the conference on the `Concept for Integrated Environmental Monitoring` and the final report `Specification of the Concept for Integrated Environmental Monitoring from the Perspective of Nature Conservation`. (orig.)

  19. Integrated care for diabetes - The Singapore Approach

    Directory of Open Access Journals (Sweden)

    Su Qian Yeo

    2012-03-01

    Full Text Available Background The prevalence of diabetes mellitus is 12.7% in Singapore. Managing people with diabetes in the community may be needed to reduce unnecessary utilisation of expensive specialist resources and to reduce hospital waiting times for patients with complications. Care Practice The Singapore General Hospital (SGH Delivering on Target (DOT Programme was launched in 2005 to right-site clinically stable diabetic patients from the hospital to private DOT GPs. The Chronic Disease Management Office (CDMO was established and a fully customised DOT information technology (IT system was developed. Three initiatives were implemented: (i Subsidised Drug Delivery Programme, (ii Diagnostic Tests Incentive Programme, and (iii Allied Healthcare Incentive Programme. Discussion Right-siting was enabled through patient incentives that eased the burden of out-of-pocket expenditure. Right Siting Officers (RSOs maintained a general oversight of the patient pathway. The integrated system supported shared care follow-up by enabling DOT GPs to share updates on the patients' health status with the referring specialists. Conclusion A coherent process across all healthcare providers similar to the SGH DOT Programme may facilitate efforts to shift the care for people with diabetes to the community and to provide integrated care. Successful integration may require incentives for institutional partners and patients.

  20. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    -genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost....... Pan-genome analyses of the global representative H. pylori isolates consisting of 39 complete genomes are presented in this paper. Phylogenetic analyses have revealed close relationships among geographically diverse strains of H. pylori. The conservation among these genomes was further analyzed by pan...

  1. Rationale for an integrated approach to genetic epidemiology.

    Science.gov (United States)

    Laberge, Claude M; Knoppers, Bartha Maria

    1992-10-01

    Genetic knowledge is now in the public domain and its interpretation by the media and the citizens brings the issues into the public forum of discussion for the necessary ethical, legal and socio-cultural evaluation of its application. Science is being perceived by some as dangerous and as requiring international regulation. Others feel that genetic knowledge will be the breakthrough that will permit medical progress and individual autonomy with regards to personal health and lifestyle choices. The mapping of the human genome has already yielded valuable information on an increasing number of diseases and their variants. Prevailing popular and journalistic archetypes ("imaginaires") used in the media are perceived by the producers as slowing down the possible application of genetic knowledge. The answers to these dilemmas are not readily apparent nor are they prescribed by classical philosophy of medicine. Since genetic knowledge eventually resides with the individual who carries the genes of disease and/or susceptibility, a logical approach to integration of this knowledge at a societal level would seem to reside with individual education and decision-making. The politics of the ensuing social debate could transform the current social contract since an individual's interests need to be balanced against those of his or her immediate family in the sharing of information. The ethical foundations of such a contract requires the genetic education of "Everyone" as a matter of urgent priority. Genetic education should not serve ideological power struggles between the medical establishment and the ethical-legal alliance. Instead, it should ensure the transfer of knowledge to physicians, to patients, to users, to planners, to social science and humanities researchers and to politicians, so that they may make "informed" and free decisions....

  2. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

    Science.gov (United States)

    Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-01-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

  3. saSNP Approach for Scalable SNP Analyses of Multiple Bacterial or Viral Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, Shea [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Slezak, Tom [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2010-07-27

    With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs. The method is fast to compute, finding SNPs and building a SNP phylogeny in seconds to hours. We use it to identify thousands of putative SNPs from all publicly available Filoviridae, Poxviridae, foot-and-mouth disease virus, Bacillus, and Escherichia coli genomes and plasmids. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle as input hundreds of gigabases of sequence in a single run. The algorithm is based on k-mer analysis using a suffix array, so we call it saSNP.

  4. Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

    The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

  5. Efficient genome-wide genotyping strategies and data integration in crop plants.

    Science.gov (United States)

    Torkamaneh, Davoud; Boyle, Brian; Belzile, François

    2018-03-01

    Next-generation sequencing (NGS) has revolutionized plant and animal research by providing powerful genotyping methods. This review describes and discusses the advantages, challenges and, most importantly, solutions to facilitate data processing, the handling of missing data, and cross-platform data integration. Next-generation sequencing technologies provide powerful and flexible genotyping methods to plant breeders and researchers. These methods offer a wide range of applications from genome-wide analysis to routine screening with a high level of accuracy and reproducibility. Furthermore, they provide a straightforward workflow to identify, validate, and screen genetic variants in a short time with a low cost. NGS-based genotyping methods include whole-genome re-sequencing, SNP arrays, and reduced representation sequencing, which are widely applied in crops. The main challenges facing breeders and geneticists today is how to choose an appropriate genotyping method and how to integrate genotyping data sets obtained from various sources. Here, we review and discuss the advantages and challenges of several NGS methods for genome-wide genetic marker development and genotyping in crop plants. We also discuss how imputation methods can be used to both fill in missing data in genotypic data sets and to integrate data sets obtained using different genotyping tools. It is our hope that this synthetic view of genotyping methods will help geneticists and breeders to integrate these NGS-based methods in crop plant breeding and research.

  6. Accounting for linkage disequilibrium in genome scans for selection without individual genotypes: The local score approach.

    Science.gov (United States)

    Fariello, María Inés; Boitard, Simon; Mercier, Sabine; Robelin, David; Faraut, Thomas; Arnould, Cécile; Recoquillay, Julien; Bouchez, Olivier; Salin, Gérald; Dehais, Patrice; Gourichon, David; Leroux, Sophie; Pitel, Frédérique; Leterrier, Christine; SanCristobal, Magali

    2017-07-01

    Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal. Using computer simulations, we demonstrate that this approach detects selection with higher power than several state-of-the-art single-marker, windowing or haplotype-based approaches. We illustrate this on two benchmark data sets including individual genotypes, for which we obtain similar results with the local score and one haplotype-based approach. Finally, we apply the local score approach to Pool-Seq data obtained from a divergent selection experiment on behaviour in quail and obtain precise and biologically coherent selection signals: while competing methods fail to highlight any clear selection signature, our method detects several regions involving genes known to act on social responsiveness or autistic traits. Although we focus here on the detection of positive selection from multiple population data, the local score approach is general and can be applied to other genome scans for selection or other genomewide analyses such as GWAS. © 2017 John Wiley & Sons Ltd.

  7. Alcoholism: integrating approaches to influence policy

    African Journals Online (AJOL)

    Adele

    Most importantly that these disorders are treatable and treatment can be cost effective. It is crucial that we continually challenge our assumptions of best treatment practices. Rehabilitation programs in the. USA have in the last decade radically changed their approach to treatment, providing most treatment in ambulatory reha ...

  8. Founding Editorial: Embryology — An Integrated Approach

    Directory of Open Access Journals (Sweden)

    Michael Richardson

    2001-01-01

    Full Text Available We introduce the Embryology domain of TheScientificWorld and outline the scope and aims. We argue for an interdisciplinary approach to problems in develop-mental biology. Three areas are identified as being of particular relevance to this domain: evolutionary developmental biology, teratology, and descriptive or experimental embryology.

  9. New Theoretical Approach Integrated Education and Technology

    Science.gov (United States)

    Ding, Gang

    2010-01-01

    The paper focuses on exploring new theoretical approach in education with development of online learning technology, from e-learning to u-learning and virtual reality technology, and points out possibilities such as constructing a new teaching ecological system, ubiquitous educational awareness with ubiquitous technology, and changing the…

  10. Integrated approach to transmission services pricing

    International Nuclear Information System (INIS)

    Yu, C.W.; David, A.K.

    1999-01-01

    The paper presents an intuitively logical split between: (a) embedded, (b) operating, and (c) expansion cost based pricing and methodologies for implementation, for transmission services. A conceptually straightforward mechanism for the equitable allocation of transmission network embedded cost recovery based on capacity-use and reliability benefit is proposed, expansion cost is charged on a long-run marginal cost basis and finally, operating cost recovery is based on short-run marginal pricing. This is followed by co-ordinating these alternatives and integrating the pricing mechanisms to achieve appropriate price signals for bulk power users of transmission systems. (author)

  11. MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.

    Science.gov (United States)

    Das, Mitali; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

    2014-01-01

    As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2-7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the "MCM paradox." Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.

  12. Critical Perspectives of Pedagogical Approaches to Reversing the Order of Integration in Double Integrals

    Science.gov (United States)

    Tisdell, Christopher C.

    2017-01-01

    This paper presents some critical perspectives regarding pedagogical approaches to the method of reversing the order of integration in double integrals from prevailing educational literature on multivariable calculus. First, we question the message found in popular textbooks that the traditional process of reversing the order of integration is…

  13. Single Cell Genomics: Approaches and Utility in Immunology

    Science.gov (United States)

    Neu, Karlynn E; Tang, Qingming; Wilson, Patrick C; Khan, Aly A

    2017-01-01

    Single cell genomics offers powerful tools for studying lymphocytes, which make it possible to observe rare and intermediate cell states that cannot be resolved at the population-level. Advances in computer science and single cell sequencing technology have created a data-driven revolution in immunology. The challenge for immunologists is to harness computing and turn an avalanche of quantitative data into meaningful discovery of immunological principles, predictive models, and strategies for therapeutics. Here, we review the current literature on computational analysis of single cell RNA-seq data and discuss underlying assumptions, methods, and applications in immunology, and highlight important directions for future research. PMID:28094102

  14. Crowdfunding the Azolla fern genome project: a grassroots approach.

    Science.gov (United States)

    Li, Fay-Wei; Pryer, Kathleen M

    2014-01-01

    Much of science progresses within the tight boundaries of what is often seen as a "black box". Though familiar to funding agencies, researchers and the academic journals they publish in, it is an entity that outsiders rarely get to peek into. Crowdfunding is a novel means that allows the public to participate in, as well as to support and witness advancements in science. Here we describe our recent crowdfunding efforts to sequence the Azolla genome, a little fern with massive green potential. Crowdfunding is a worthy platform not only for obtaining seed money for exploratory research, but also for engaging directly with the general public as a rewarding form of outreach.

  15. Undergraduate hematology – a more integrated approach

    Directory of Open Access Journals (Sweden)

    Di Carlofelice MA

    2016-11-01

    Full Text Available Matteo A Di Carlofelice,* Jack FT Cope*Faculty of Medicine, Imperial College London, London, UK*These authors contributed equally to this workAs fellow medical students we read with great interest the article by Mandan et al1 proposing a dedicated hematology rotation. The authors highlight a gap in clinical hematology teaching, particularly compared to “conventional rotations”.1 Their suggestion has merits and we agree with most of the points raised; however, propose instead for us to build on current teaching as opposed to establishing a new rotation.The integration of theoretical and practical learning was concluded to be beneficial to both teacher and student by Wrenn and Wrenn.2 In the original article it is mentioned that “clinical experience allows students to comprehend and apply this knowledge in practice, enabling the all-important integration of their learning”.1 As we agree that hematology overlaps with other specialties and therefore requires a thorough understanding, we value how a clinical attachment would be useful to solidify lecture-based teaching.View the original paper by Mandan et al.

  16. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

    Science.gov (United States)

    Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

    2012-12-15

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

  17. A New Approach to Dissect Nuclear Organization: TALE-Mediated Genome Visualization (TGV).

    Science.gov (United States)

    Miyanari, Yusuke

    2016-01-01

    Spatiotemporal organization of chromatin within the nucleus has so far remained elusive. Live visualization of nuclear remodeling could be a promising approach to understand its functional relevance in genome functions and mechanisms regulating genome architecture. Recent technological advances in live imaging of chromosomes begun to explore the biological roles of the movement of the chromatin within the nucleus. Here I describe a new technique, called TALE-mediated genome visualization (TGV), which allows us to visualize endogenous repetitive sequence including centromeric, pericentromeric, and telomeric repeats in living cells.

  18. Drosophila Sld5 is essential for normal cell cycle progression and maintenance of genomic integrity

    Energy Technology Data Exchange (ETDEWEB)

    Gouge, Catherine A. [Department of Biology, East Carolina University East Carolina University, Greenville, NC 27858 (United States); Christensen, Tim W., E-mail: christensent@ecu.edu [Department of Biology, East Carolina University East Carolina University, Greenville, NC 27858 (United States)

    2010-09-10

    Research highlights: {yields} Drosophila Sld5 interacts with Psf1, PPsf2, and Mcm10. {yields} Haploinsufficiency of Sld5 leads to M-phase delay and genomic instability. {yields} Sld5 is also required for normal S phase progression. -- Abstract: Essential for the normal functioning of a cell is the maintenance of genomic integrity. Failure in this process is often catastrophic for the organism, leading to cell death or mis-proliferation. Central to genomic integrity is the faithful replication of DNA during S phase. The GINS complex has recently come to light as a critical player in DNA replication through stabilization of MCM2-7 and Cdc45 as a member of the CMG complex which is likely responsible for the processivity of helicase activity during S phase. The GINS complex is made up of 4 members in a 1:1:1:1 ratio: Psf1, Psf2, Psf3, And Sld5. Here we present the first analysis of the function of the Sld5 subunit in a multicellular organism. We show that Drosophila Sld5 interacts with Psf1, Psf2, and Mcm10 and that mutations in Sld5 lead to M and S phase delays with chromosomes exhibiting hallmarks of genomic instability.

  19. Genome puzzle master (GPM): an integrated pipeline for building and editing pseudomolecules from fragmented sequences.

    Science.gov (United States)

    Zhang, Jianwei; Kudrna, Dave; Mu, Ting; Li, Weiming; Copetti, Dario; Yu, Yeisoo; Goicoechea, Jose Luis; Lei, Yang; Wing, Rod A

    2016-10-15

    Next generation sequencing technologies have revolutionized our ability to rapidly and affordably generate vast quantities of sequence data. Once generated, raw sequences are assembled into contigs or scaffolds. However, these assemblies are mostly fragmented and inaccurate at the whole genome scale, largely due to the inability to integrate additional informative datasets (e.g. physical, optical and genetic maps). To address this problem, we developed a semi-automated software tool-Genome Puzzle Master (GPM)-that enables the integration of additional genomic signposts to edit and build 'new-gen-assemblies' that result in high-quality 'annotation-ready' pseudomolecules. With GPM, loaded datasets can be connected to each other via their logical relationships which accomplishes tasks to 'group,' 'merge,' 'order and orient' sequences in a draft assembly. Manual editing can also be performed with a user-friendly graphical interface. Final pseudomolecules reflect a user's total data package and are available for long-term project management. GPM is a web-based pipeline and an important part of a Laboratory Information Management System (LIMS) which can be easily deployed on local servers for any genome research laboratory. The GPM (with LIMS) package is available at https://github.com/Jianwei-Zhang/LIMS CONTACTS: jzhang@mail.hzau.edu.cn or rwing@mail.arizona.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  20. RGmatch: matching genomic regions to proximal genes in omics data integration

    Directory of Open Access Journals (Sweden)

    Pedro Furió-Tarí

    2016-11-01

    Full Text Available Abstract Background The integrative analysis of multiple genomics data often requires that genome coordinates-based signals have to be associated with proximal genes. The relative location of a genomic region with respect to the gene (gene area is important for functional data interpretation; hence algorithms that match regions to genes should be able to deliver insight into this information. Results In this work we review the tools that are publicly available for making region-to-gene associations. We also present a novel method, RGmatch, a flexible and easy-to-use Python tool that computes associations either at the gene, transcript, or exon level, applying a set of rules to annotate each region-gene association with the region location within the gene. RGmatch can be applied to any organism as long as genome annotation is available. Furthermore, we qualitatively and quantitatively compare RGmatch to other tools. Conclusions RGmatch simplifies the association of a genomic region with its closest gene. At the same time, it is a powerful tool because the rules used to annotate these associations are very easy to modify according to the researcher’s specific interests. Some important differences between RGmatch and other similar tools already in existence are RGmatch’s flexibility, its wide range of user options, compatibility with any annotatable organism, and its comprehensive and user-friendly output.

  1. FISH Oracle 2: a web server for integrative visualization of genomic data in cancer research.

    Science.gov (United States)

    Mader, Malte; Simon, Ronald; Kurtz, Stefan

    2014-03-31

    A comprehensive view on all relevant genomic data is instrumental for understanding the complex patterns of molecular alterations typically found in cancer cells. One of the most effective ways to rapidly obtain an overview of genomic alterations in large amounts of genomic data is the integrative visualization of genomic events. We developed FISH Oracle 2, a web server for the interactive visualization of different kinds of downstream processed genomics data typically available in cancer research. A powerful search interface and a fast visualization engine provide a highly interactive visualization for such data. High quality image export enables the life scientist to easily communicate their results. A comprehensive data administration allows to keep track of the available data sets. We applied FISH Oracle 2 to published data and found evidence that, in colorectal cancer cells, the gene TTC28 may be inactivated in two different ways, a fact that has not been published before. The interactive nature of FISH Oracle 2 and the possibility to store, select and visualize large amounts of downstream processed data support life scientists in generating hypotheses. The export of high quality images supports explanatory data visualization, simplifying the communication of new biological findings. A FISH Oracle 2 demo server and the software is available at http://www.zbh.uni-hamburg.de/fishoracle.

  2. Leisure market segmentation : an integrated preferences/constraints-based approach

    NARCIS (Netherlands)

    Stemerding, M.P.; Oppewal, H.; Beckers, T.A.M.; Timmermans, H.J.P.

    1996-01-01

    Traditional segmentation schemes are often based on a grouping of consumers with similar preference functions. The research steps, ultimately leading to such segmentation schemes, are typically independent. In the present article, a new integrated approach to segmentation is introduced, which

  3. SESSION V: INTEGRATED APPROACHES IN LAND AND WATER ...

    African Journals Online (AJOL)

    SESSION V: INTEGRATED APPROACHES IN LAND AND WATER MANAGEMENT RESEARCH/LAND AND WATER MANAGEMENT ECONOMICS AND POLICY - Socioeconomic implications of improved forage species on smallholder farms in Kenya.

  4. Integration of case study approach, project design and computer ...

    African Journals Online (AJOL)

    Integration of case study approach, project design and computer modeling in managerial accounting education ... Journal of Fundamental and Applied Sciences ... in the Laboratory of Management Accounting and Controlling Systems at the ...

  5. Integrated landscape approach : Closing the gap between theory and application

    NARCIS (Netherlands)

    Bürgi, Matthias; Ali, Panna; Chowdhury, Afroza; Heinimann, Andreas; Hett, Cornelia; Kienast, Felix; Mondal, Manoranjan Kumar; Upreti, Bishnu Raj; Verburg, Peter H.

    2017-01-01

    Recently, the integrated landscape approach has gained increasing interest of the scientific community, as well as of organizations active in the field of sustainable development. However, the enthusiastic welcome is challenged by little consensus on theory, terminology and definitions. Moreover,

  6. Germline transgenic pigs by Sleeping Beauty transposition in porcine zygotes and targeted integration in the pig genome.

    Directory of Open Access Journals (Sweden)

    Wiebke Garrels

    Full Text Available Genetic engineering can expand the utility of pigs for modeling human diseases, and for developing advanced therapeutic approaches. However, the inefficient production of transgenic pigs represents a technological bottleneck. Here, we assessed the hyperactive Sleeping Beauty (SB100X transposon system for enzyme-catalyzed transgene integration into the embryonic porcine genome. The components of the transposon vector system were microinjected as circular plasmids into the cytoplasm of porcine zygotes, resulting in high frequencies of transgenic fetuses and piglets. The transgenic animals showed normal development and persistent reporter gene expression for >12 months. Molecular hallmarks of transposition were confirmed by analysis of 25 genomic insertion sites. We demonstrate germ-line transmission, segregation of individual transposons, and continued, copy number-dependent transgene expression in F1-offspring. In addition, we demonstrate target-selected gene insertion into transposon-tagged genomic loci by Cre-loxP-based cassette exchange in somatic cells followed by nuclear transfer. Transposase-catalyzed transgenesis in a large mammalian species expands the arsenal of transgenic technologies for use in domestic animals and will facilitate the development of large animal models for human diseases.

  7. Path integral approach to multidimensional quantum tunnelling

    International Nuclear Information System (INIS)

    Balantekin, A.B.; Takigawa, N.

    1985-01-01

    Path integral formulation of the coupled channel problem in the case of multidimensional quantum tunneling is presented and two-time influence functionals are introduced. The two-time influence functionals are calculated explicitly for the three simplest cases: Harmonic oscillators linearly or quadratically coupled to the translational motion and a system with finite number of equidistant energy levels linearly coupled to the translational motion. The effects of these couplings on the transmission probability are studied for two limiting cases, adiabatic case and when the internal system has a degenerate energy spectrum. The condition for the transmission probability to show a resonant structure is discussed and exemplified. Finally, the properties of the dissipation factor in the adiabatic limit and its correlation with the friction coefficient in the classically accessible region are studied

  8. Aluminum recycling—An integrated, industrywide approach

    Science.gov (United States)

    Das, Subodh K.; Green, John A. S.; Kaufman, J. Gilbert; Emadi, Daryoush; Mahfoud, M.

    2010-02-01

    The aluminum industry is a leading proponent of global sustainability and strongly advocates the use of recycled metal. As the North American primary aluminum industry continues to move offshore to other geographic areas such as Iceland and the Middle East, where energy is more readily available at lower cost, the importance of the secondary (i.e., recycled metal) market in the U.S. will continue to increase. The purpose of this paper is to take an integrated, industry-wide look at the recovery of material from demolished buildings, shredded automobiles, and aging aircraft, as well as from traditional cans and other rigid containers. Attempts will be made to assess how the different alloys used in these separate markets can be recycled in the most energy-efficient manner.

  9. A boundary integral approach to unstable solidification

    International Nuclear Information System (INIS)

    Strain, J.

    1989-01-01

    We consider the supercooled Stefan problem with a general anisotropic curvature- and velocity-dependent boundary condition on the moving interface. We present numerical methods, based on an integral equation formulation and including a new algorithm for moving curves with curvature-dependent velocity. These methods compute a periodic interface with O(Δt) accuracy, where Δt is the time step. Previous work has been limited to short time spans and achieved slightly less than O(Δt 1/2 ) accuracy. Accurate numerical results are seen to agree with the predictions of linear stability theory. This agreement has eluded previous authors, because their numerical methods suffered from grid effects and their linear stability theory was incorrect. We study the long-time evolution of an unstable interface. Our computations exhibit the beginnings of a sidebranching instability when the boundary condition includes anisotropy and tip-splitting in the isotropic case. copyright 1989 Academic Press, Inc

  10. An integrated approach for prioritized process improvement.

    Science.gov (United States)

    Vanteddu, Gangaraju; McAllister, Charles D

    2014-01-01

    The purpose of this paper is to propose an integrated framework to simultaneously identify and improve healthcare processes that are important from the healthcare provider's and patient's perspectives. A modified quality function deployment (QFD) chart is introduced to the field of healthcare quality assurance. A healthcare service example is used to demonstrate the utility of the proposed chart. The proposed framework is versatile and can be used in a wide variety of healthcare quality improvement contexts, wherein, two different perspectives are needed to be considered for identifying and improving critical healthcare processes. The modified QFD chart used in conjunction with the stacked Pareto chart will facilitate the identification of key performance metrics from the patient's and the hospital's perspectives. Subsequently, the chief contributory factors at different levels are identified in a very efficient manner. Healthcare quality improvement professionals will be able to use the proposed modified QFD chart in association with stacked Pareto chart for effective quality assurance.

  11. 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 curre......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...... 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....

  12. Regional Integrated Silvopastoral Approaches to Ecosystem Management Project

    OpenAIRE

    CIPAV (Centre For Research on Sustainable Agricultural Production Systems); CATIE (Centro Agronomico Tropical de Investigacion y Ensenanza); NITLAPAN

    2007-01-01

    Metadata only record The Regional Integrated Silvopastoral Approaches to Ecosystem Management Project introduces the payment for environmental services approach to silvopastoral farmers in Colombia, Costa Rica, and Nicaragua. The objectives of the project are to "demonstrate and measure a) the effects the introduction of payment incentives for environmental services to farmers on their adoption of integrated silvopastoral farming systems in degraded pasture lands; and b) the resulting impr...

  13. Integrative approaches to childhood constipation and encopresis.

    Science.gov (United States)

    Culbert, Timothy P; Banez, Gerard A

    2007-12-01

    Constipation and encopresis (fecal soiling) are common childhood disorders that may lead to significant functional impairment. The etiology and course of constipation and encopresis are increasingly conceptualized from a broad biopsychosocial perspective, and therefore a holistic approach to assessment and treatment is indicated. Many children experience symptoms of chronic constipation and/or encopresis that are only partially responsive to conventional medical therapy. Complementary/alternative therapies can often help in the treatment of constipation/encopresis and are well accepted by patients and families.

  14. The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.

    Directory of Open Access Journals (Sweden)

    Maria J Aristizabal

    2015-10-01

    Full Text Available RNA polymerase II (RNAPII contains a unique C-terminal domain that is composed of heptapeptide repeats and which plays important regulatory roles during gene expression. RNAPII is responsible for the transcription of most protein-coding genes, a subset of non-coding genes, and retrotransposons. Retrotransposon transcription is the first step in their multiplication cycle, given that the RNA intermediate is required for the synthesis of cDNA, the material that is ultimately incorporated into a new genomic location. Retrotransposition can have grave consequences to genome integrity, as integration events can change the gene expression landscape or lead to alteration or loss of genetic information. Given that RNAPII transcribes retrotransposons, we sought to investigate if the RNAPII-CTD played a role in the regulation of retrotransposon gene expression. Importantly, we found that the RNAPII-CTD functioned to maintaining genome integrity through inhibition of retrotransposon gene expression, as reducing CTD length significantly increased expression and transposition rates of Ty1 elements. Mechanistically, the increased Ty1 mRNA levels in the rpb1-CTD11 mutant were partly due to Cdk8-dependent alterations to the RNAPII-CTD phosphorylation status. In addition, Cdk8 alone contributed to Ty1 gene expression regulation by altering the occupancy of the gene-specific transcription factor Ste12. Loss of STE12 and TEC1 suppressed growth phenotypes of the RNAPII-CTD truncation mutant. Collectively, our results implicate Ste12 and Tec1 as general and important contributors to the Cdk8, RNAPII-CTD regulatory circuitry as it relates to the maintenance of genome integrity.

  15. The openness of pluripotent epigenome - Defining the genomic integrity of stemness for regenerative medicine

    Directory of Open Access Journals (Sweden)

    Xuejun H Parsons

    2014-02-01

    Full Text Available This article is an editorial, and it doesn't include an abstract. Full text of this article is available in HTML and PDF.Cite this article as: Parsons XH. The openness of pluripotent epigenome - Defining the genomic Integrity of stemness for regenerative medicine. Int J Cancer Ther Oncol 2014; 2(1:020114.DOI: http://dx.doi.org/10.14319/ijcto.0201.14

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

    OpenAIRE

    Verma, Mohit; Kumar, Vinay; Patel, Ravi K.; Garg, Rohini; Jain, Mukesh

    2015-01-01

    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 fea...

  17. Integrative Bioinformatics Approaches for Identification of Drug Targets in Hypertension.

    Science.gov (United States)

    Hemerich, Daiane; van Setten, Jessica; Tragante, Vinicius; Asselbergs, Folkert W

    2018-01-01

    High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions. Phenotypic cell-type specificity analyses and expression quantitative trait loci show predominant vascular and cardiac tissue involvement for blood pressure-associated variants. Maps of chromosomal conformation and expression quantitative trait loci (eQTL) in critical tissues identified 2,424 genes interacting with blood pressure-associated loci, of which 517 are druggable. Integrating genome, regulome and transcriptome information in relevant cell-types could help to functionally annotate blood pressure associated loci and identify drug targets.

  18. SWPhylo - A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees.

    Science.gov (United States)

    Yu, Xiaoyu; Reva, Oleg N

    2018-01-01

    Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA.

  19. SWPhylo – A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees

    Science.gov (United States)

    Yu, Xiaoyu; Reva, Oleg N

    2018-01-01

    Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA. PMID:29511354

  20. 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.

  1. Approaches to the summability of divergent multidimensional integrals

    International Nuclear Information System (INIS)

    Vainikko, G M; Lifanov, I K

    2003-01-01

    Under discussion are various approaches to the concept of summability (finding the finite part - (f.p.)) of divergent integrals with integrand represented as a product of two functions, one with a parameter-dependent non-integrable singularity at one point of the integration and the other absolutely integrable. A study is made of summability methods which are based on the expansion of the absolutely integrable function in a Taylor series with centre at the singular point (f.p.), on the analytic continuation with respect to the parameter of the singularity (a.f.p.), and on integration by parts (f.p.p.). Formulae of changes of variables in such integrals are presented

  2. Whole genome sequencing: an efficient approach to ensuring food safety

    Science.gov (United States)

    Lakicevic, B.; Nastasijevic, I.; Dimitrijevic, M.

    2017-09-01

    Whole genome sequencing is an effective, powerful tool that can be applied to a wide range of public health and food safety applications. A major difference between WGS and the traditional typing techniques is that WGS allows all genes to be included in the analysis, instead of a well-defined subset of genes or variable intergenic regions. Also, the use of WGS can facilitate the understanding of contamination/colonization routes of foodborne pathogens within the food production environment, and can also afford efficient tracking of pathogens’ entry routes and distribution from farm-to-consumer. Tracking foodborne pathogens in the food processing-distribution-retail-consumer continuum is of the utmost importance for facilitation of outbreak investigations and rapid action in controlling/preventing foodborne outbreaks. Therefore, WGS likely will replace most of the numerous workflows used in public health laboratories to characterize foodborne pathogens into one consolidated, efficient workflow.

  3. Single-Cell Genomics: Approaches and Utility in Immunology.

    Science.gov (United States)

    Neu, Karlynn E; Tang, Qingming; Wilson, Patrick C; Khan, Aly A

    2017-02-01

    Single-cell genomics offers powerful tools for studying immune cells, which make it possible to observe rare and intermediate cell states that cannot be resolved at the population level. Advances in computer science and single-cell sequencing technology have created a data-driven revolution in immunology. The challenge for immunologists is to harness computing and turn an avalanche of quantitative data into meaningful discovery of immunological principles, predictive models, and strategies for therapeutics. Here, we review the current literature on computational analysis of single-cell RNA-sequencing data and discuss underlying assumptions, methods, and applications in immunology, and highlight important directions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Integrating lifestyle approaches into osteoarthritis care

    Directory of Open Access Journals (Sweden)

    Garver MJ

    2015-09-01

    Full Text Available Matthew J Garver,1 Brian C Focht,2 Sarah J Taylor3 1Department of Kinesiology and Nutrition, Abilene Christian University, Abilene, TX, 2Department of Human Sciences, Ohio State University, Columbus, OH, 3School of Occupational Therapy, Texas Woman's University, Dallas, TX, USA Abstract: As the lifetime risk, societal cost, and overall functional impact of osteoarthritis (OA is imposing, it is imperative that clinicians provide an individualized care model for patients. Patients must be offered a multiplicity of care strategies and encouraged to embrace lifestyle approaches for self-managing the effects and symptoms of OA. Certainly, the attitude of the clinician and patient will directly influence receptivity and implementation of lifestyle approaches. This work proposes how the use of structured and routine assessments and cognitive therapy ideologies may complement a comprehensive treatment plan. Assessments described herein include objective and/or self-report measures of physical function, pain, attitude about social support, and sleep quality. Baseline assessments followed by systematic monitoring of the results may give patients and clinicians valuable insight into the effectiveness of the care plan. Empirical evidence from randomized trials with OA patients highlights the effectiveness of cognitive behavioral change strategies for addressing salient concerns for OA (pain control, mobility performance, and sleep quality. Cognitive restructuring can provide patients with renewed power in managing their disease. Cognitive therapy topics discussed presently include: 1 what is OA?, 2 effectiveness of exercise and FITT (frequency, intensity, time, and type principles for OA patients, 3 goal-setting and barriers, and 4 translating to independent care. Woven within the discussion about cognitive therapy are ideas about how the results from baseline assessments and group-mediated dynamics might assist more favorable outcomes. There are a plethora

  5. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  6. Integrated microsystems packaging approach with LCP

    Science.gov (United States)

    Jaynes, Paul; Shacklette, Lawrence W.

    2006-05-01

    Within the government communication market there is an increasing push to further miniaturize systems with the use of chip-scale packages, flip-chip bonding, and other advances over traditional packaging techniques. Harris' approach to miniaturization includes these traditional packaging advances, but goes beyond this level of miniaturization by combining the functional and structural elements of a system, thus creating a Multi-Functional Structural Circuit (MFSC). An emerging high-frequency, near hermetic, thermoplastic electronic substrate material, Liquid Crystal Polymer (LCP), is the material that will enable the combination of the electronic circuit and the physical structure of the system. The first embodiment of this vision for Harris is the development of a battlefield acoustic sensor module. This paper will introduce LCP and its advantages for MFSC, present an example of the work that Harris has performed, and speak to LCP MFSCs' potential benefits to miniature communications modules and sensor platforms.

  7. AN INTEGRATED APPROACH FOR LINKED DATA BROWSING

    Directory of Open Access Journals (Sweden)

    W. Beek

    2017-07-01

    Full Text Available The Netherlands' Cadastre, Land Registry and Mapping Agency – in short Kadaster – collects and registers administrative and spatial data on property and the rights involved. Currently, the Kadaster is publishing its geo-spatial data assets as Linked Open Data. The Kadaster manages hundreds of datasets that describe hundreds of millions of geospatial objects, including all Dutch buildings, roads, and forests. The Kadaster exposes this large collection of data to thousands of daily users that operate from within different contexts and that need to be supported in different use cases. Therefore, Kadaster must offer diverse, yet complementary, approaches for browsing and exploring the data it publishes. Specifically, it supports the following paradigms for browsing and exploring its data assets: hierarchical browsing, graph navigation, faceted browsing, and tabular browsing. These paradigms are useful for different tasks, cover different use cases, and are implemented by reusing and/or developing Open Source libraries and applications.

  8. Preregularization and the path integral approach to the chiral anomaly

    International Nuclear Information System (INIS)

    Elias, V.; McKeon, G.; Steele, T.; Mann, R.B.; Treml, T.F.; Sherry, T.N.

    1987-01-01

    We explore the connection between perturbative and non-perturbative (path-integral) approaches to the axial anomaly. In particular, we show how the Jacobian associated with the fermionic measure corresponding to local axial transformations may be calculated directly from shift-of-integration-variable surface terms in four Euclidean dimensions. No regularization (explicit parametrization of UV infinities) is required in this approach, but invariance of the Jacobian under vector gauge transformations (i.e. preregularization) is required to remove a variable-of-integration ambiguity within the expression for the Jacobian of the fermionic measure. (orig.)

  9. 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.

  10. CRISPR/Cas9: A Practical Approach in Date Palm Genome Editing

    Directory of Open Access Journals (Sweden)

    Muhammad N. Sattar

    2017-08-01

    Full Text Available The genetic modifications through breeding of crop plants have long been used to improve the yield and quality. However, precise genome editing (GE could be a very useful supplementary tool for improvement of crop plants by targeted genome modifications. Various GE techniques including ZFNs (zinc finger nucleases, TALENs (transcription activator-like effector nucleases, and most recently clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 (CRISPR-associated protein 9-based approaches have been successfully employed for various crop plants including fruit trees. CRISPR/Cas9-based approaches hold great potential in GE due to their simplicity, competency, and versatility over other GE techniques. However, to the best of our knowledge no such genetic improvement has ever been developed in date palm—an important fruit crop in Oasis agriculture. The applications of CRISPR/Cas9 can be a challenging task in date palm GE due to its large and complex genome, high rate of heterozygosity and outcrossing, in vitro regeneration and screening of mutants, high frequency of single-nucleotide polymorphism in the genome and ultimately genetic instability. In this review, we addressed the potential application of CRISPR/Cas9-based approaches in date palm GE to improve the sustainable date palm production. The availability of the date palm whole genome sequence has made it feasible to use CRISPR/Cas9 GE approach for genetic improvement in this species. Moreover, the future prospects of GE application in date palm are also addressed in this review.

  11. An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome

    NARCIS (Netherlands)

    Fox, J.E.; Bridgham, J.T.; Bovee, T.F.H.; Thornton, J.W.

    2007-01-01

    To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a

  12. The integrated approach methodology for operator information evaluation

    International Nuclear Information System (INIS)

    Stroube, K.; Modarres, M.; Roush, M.; Hunt, N.; Pearce, R.

    1986-01-01

    The Integrated Approach has developed a complete method for evaluating the relative importance of operation information improvements. By use of decision trees the impact of information on success probability of a function or system can be evaluated. This approach couples goal trees and human success likelihoods to estimate anticipated consequences of a given information system

  13. Towards an integrated approach to health and medicine in Africa

    African Journals Online (AJOL)

    2016-08-18

    Aug 18, 2016 ... As such, a social approach to health-seeking behaviour questions how decisions ... In conclusion, the paper proposes that medicine and the humanities should engage seriously .... mental questions: What story does the integration or separation .... approach which has taken an interest in traditional healing.

  14. Learning about the Weather through an Integrated STEM Approach

    Science.gov (United States)

    Serin, Gokhan

    2014-01-01

    Introducing concepts through an integrated science, technology, engineering and mathematics (STEM) approach can promote interest and motivation (Bennett, Lubben and Hogarth, 2007; Bybee, 2010). However, implementing such an approach effectively in a classroom setting, with relevant links, is a challenging task. Some concepts lend themselves more…

  15. An integrated artificial neural networks approach for predicting global radiation

    International Nuclear Information System (INIS)

    Azadeh, A.; Maghsoudi, A.; Sohrabkhani, S.

    2009-01-01

    This article presents an integrated artificial neural network (ANN) approach for predicting solar global radiation by climatological variables. The integrated ANN trains and tests data with multi layer perceptron (MLP) approach which has the lowest mean absolute percentage error (MAPE). The proposed approach is particularly useful for locations where no available measurement equipment. Also, it considers all related climatological and meteorological parameters as input variables. To show the applicability and superiority of the integrated ANN approach, monthly data were collected for 6 years (1995-2000) in six nominal cities in Iran. Separate model for each city is considered and the quantity of solar global radiation in each city is calculated. Furthermore an integrated ANN model has been introduced for prediction of solar global radiation. The acquired results of the integrated model have shown high accuracy of about 94%. The results of the integrated model have been compared with traditional angstrom's model to show its considerable accuracy. Therefore, the proposed approach can be used as an efficient tool for prediction of solar radiation in the remote and rural locations with no direct measurement equipment.

  16. Integrated, regional approach to risk management of industrial systems

    International Nuclear Information System (INIS)

    Chakraborty, S.

    1992-01-01

    This paper focuses on the following four main issues: (1) necessity for an integrated, regional approach to risk management of industrial systems; (2) principles of risk management; (3) integrated approach and overall methodology; and (4) implementation of risk management strategies on a regional basis. The U.N. Interagency project on risk management for large industrial areas, which is a pioneer type of international initiative for an integrated approach to risk management, is discussed in this context. Another encouraging activity for further development of overall methodologies for risk management is the ongoing project on the risk and safety of technical systems at the Swiss Federal Institute of Technology in Aurich. The concept of integral risk management takes into account multidimensional factors including technical, economic, political, social, and ethical considerations to allow a well-balanced decision-making process

  17. 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

  18. 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.

  19. Gain-of-function mutagenesis approaches in rice for functional genomics and improvement of crop productivity.

    Science.gov (United States)

    Moin, Mazahar; Bakshi, Achala; Saha, Anusree; Dutta, Mouboni; Kirti, P B

    2017-07-01

    The epitome of any genome research is to identify all the existing genes in a genome and investigate their roles. Various techniques have been applied to unveil the functions either by silencing or over-expressing the genes by targeted expression or random mutagenesis. Rice is the most appropriate model crop for generating a mutant resource for functional genomic studies because of the availability of high-quality genome sequence and relatively smaller genome size. Rice has syntenic relationships with members of other cereals. Hence, characterization of functionally unknown genes in rice will possibly provide key genetic insights and can lead to comparative genomics involving other cereals. The current review attempts to discuss the available gain-of-function mutagenesis techniques for functional genomics, emphasizing the contemporary approach, activation tagging and alterations to this method for the enhancement of yield and productivity of rice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. 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.

  1. Functional Associations by Response Overlap (FARO, a functional genomics approach matching gene expression phenotypes.

    Directory of Open Access Journals (Sweden)

    Henrik Bjørn Nielsen

    2007-08-01

    Full Text Available The systematic comparison of transcriptional responses of organisms is a powerful tool in functional genomics. For example, mutants may be characterized by comparing their transcript profiles to those obtained in other experiments querying the effects on gene expression of many experimental factors including treatments, mutations and pathogen infections. Similarly, drugs may be discovered by the relationship between the transcript profiles effectuated or impacted by a candidate drug and by the target disease. The integration of such data enables systems biology to predict the interplay between experimental factors affecting a biological system. Unfortunately, direct comparisons of gene expression profiles obtained in independent, publicly available microarray experiments are typically compromised by substantial, experiment-specific biases. Here we suggest a novel yet conceptually simple approach for deriving 'Functional Association(s by Response Overlap' (FARO between microarray gene expression studies. The transcriptional response is defined by the set of differentially expressed genes independent from the magnitude or direction of the change. This approach overcomes the limited comparability between studies that is typical for methods that rely on correlation in gene expression. We apply FARO to a compendium of 242 diverse Arabidopsis microarray experimental factors, including phyto-hormones, stresses and pathogens, growth conditions/stages, tissue types and mutants. We also use FARO to confirm and further delineate the functions of Arabidopsis MAP kinase 4 in disease and stress responses. Furthermore, we find that a large, well-defined set of genes responds in opposing directions to different stress conditions and predict the effects of different stress combinations. This demonstrates the usefulness of our approach for exploiting public microarray data to derive biologically meaningful associations between experimental factors. Finally, our

  2. Recent developments in the path integral approach to anomalies

    International Nuclear Information System (INIS)

    Fujikawa, Kazuo.

    1986-08-01

    After a brief summary of the path integral approach to anomalous identities, some of the recent developments in this approach are discussed. The topics discussed include (i) Construction of the effective action by means of the covariant current, (ii) Gauss law constraint in anomalous gauge theories, (iii) Path integral approach to anomalies in superconformal transformations, (iv) Conformal and ghost number anomalies in string theory in analogy with the instanton calculation, (v) Covariant local Lorentz anomaly and its connection with the mathematical construction of the consistent anomaly. (author)

  3. High resolution integral holography using Fourier ptychographic approach.

    Science.gov (United States)

    Li, Zhaohui; Zhang, Jianqi; Wang, Xiaorui; Liu, Delian

    2014-12-29

    An innovative approach is proposed for calculating high resolution computer generated integral holograms by using the Fourier Ptychographic (FP) algorithm. The approach initializes a high resolution complex hologram with a random guess, and then stitches together low resolution multi-view images, synthesized from the elemental images captured by integral imaging (II), to recover the high resolution hologram through an iterative retrieval with FP constrains. This paper begins with an analysis of the principle of hologram synthesis from multi-projections, followed by an accurate determination of the constrains required in the Fourier ptychographic integral-holography (FPIH). Next, the procedure of the approach is described in detail. Finally, optical reconstructions are performed and the results are demonstrated. Theoretical analysis and experiments show that our proposed approach can reconstruct 3D scenes with high resolution.

  4. 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.

  5. LocusTrack: Integrated visualization of GWAS results and genomic annotation.

    Science.gov (United States)

    Cuellar-Partida, Gabriel; Renteria, Miguel E; MacGregor, Stuart

    2015-01-01

    Genome-wide association studies (GWAS) are an important tool for the mapping of complex traits and diseases. Visual inspection of genomic annotations may be used to generate insights into the biological mechanisms underlying GWAS-identified loci. We developed LocusTrack, a web-based application that annotates and creates plots of regional GWAS results and incorporates user-specified tracks that display annotations such as linkage disequilibrium (LD), phylogenetic conservation, chromatin state, and other genomic and regulatory elements. Currently, LocusTrack can integrate annotation tracks from the UCSC genome-browser as well as from any tracks provided by the user. LocusTrack is an easy-to-use application and can be accessed at the following URL: http://gump.qimr.edu.au/general/gabrieC/LocusTrack/. Users can upload and manage GWAS results and select from and/or provide annotation tracks using simple and intuitive menus. LocusTrack scripts and associated data can be downloaded from the website and run locally.

  6. Integrative Genomic and Proteomic Analysis of the Response of Lactobacillus casei Zhang to Glucose Restriction.

    Science.gov (United States)

    Yu, Jie; Hui, Wenyan; Cao, Chenxia; Pan, Lin; Zhang, Heping; Zhang, Wenyi

    2018-03-02

    Nutrient starvation is an important survival challenge for bacteria during industrial production of functional foods. As next-generation sequencing technology has greatly advanced, we performed proteomic and genomic analysis to investigate the response of Lactobacillus casei Zhang to a glucose-restricted environment. L. casei Zhang strains were permitted to evolve in glucose-restricted or normal medium from a common ancestor over a 3 year period, and they were sampled at 1000, 2000, 3000, 4000, 5000, 6000, 7000, and 8000 generations and subjected to proteomic and genomic analyses. Genomic resequencing data revealed different point mutations and other mutational events in each selected generation of L. casei Zhang under glucose restriction stress. The differentially expressed proteins induced by glucose restriction were mostly related to fructose and mannose metabolism, carbohydrate metabolic processes, lyase activity, and amino-acid-transporting ATPase activity. Integrative proteomic and genomic analysis revealed that the mutations protected L. casei Zhang against glucose starvation by regulating other cellular carbohydrate, fatty acid, and amino acid catabolism; phosphoenolpyruvate system pathway activation; glycogen synthesis; ATP consumption; pyruvate metabolism; and general stress-response protein expression. The results help reveal the mechanisms of adapting to glucose starvation and provide new strategies for enhancing the industrial utility of L. casei Zhang.

  7. 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.

  8. 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. PMID:14681437

  9. Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

    Science.gov (United States)

    Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

    2016-01-01

    To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

  10. A new Gauss quadrature for multicentre integrals over STOs in the Gaussian integral transform approach

    International Nuclear Information System (INIS)

    Bouferguene, Ahmed

    2005-01-01

    When computing multicentre integrals over Slater-type orbitals (STOs) by means of the Shavitt and Karplus Gaussian integral transforms (Shavitt and Karplus 1962 J. Chem. Phys. 36 550), one usually ends up with a multiple integral of the form ∫ 0 1 du ∫ 0 1 dv ...∫ 0 ∞ dz F(u, v, ..., z) (Shavitt and Karplus 1965 J. Chem. Phys. 43 398) in which all the integrals are inter-related. The most widely used approach for computing such an integral is to apply a product of Gauss-Legendre quadratures for the integrals over [0, 1] while the semi-infinite term is evaluated by a special procedure. Although numerous approaches have been developed to accurately perform the integration over [0, ∞) efficiently, it is the aim of this work to add a new tool that could be of some benefit in carrying out the hard task of multicentre integrals over STOs. The new approach relies on a special Gauss quadrature referred to as Gauss-Bessel to accurately evaluate the semi-infinite integral of interest. In this work, emphasis is put on accuracy rather than efficiency since its aim is essentially to bring a proof of concept showing that Gauss-Bessel quadrature can successfully be applied in the context of multicentre integrals over STOs. The obtained accuracy is comparable to that obtained with other methods available in the literature

  11. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.

    Science.gov (United States)

    Vassy, Jason L; Lautenbach, Denise M; McLaughlin, Heather M; Kong, Sek Won; Christensen, Kurt D; Krier, Joel; Kohane, Isaac S; Feuerman, Lindsay Z; Blumenthal-Barby, Jennifer; Roberts, J Scott; Lehmann, Lisa Soleymani; Ho, Carolyn Y; Ubel, Peter A; MacRae, Calum A; Seidman, Christine E; Murray, Michael F; McGuire, Amy L; Rehm, Heidi L; Green, Robert C

    2014-03-20

    illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies. ClinicalTrials.gov identifier NCT01736566.

  12. The impact of post-genomics approaches in neurodegenerative demyelinating diseases: the case of Guillain-Barré syndrome.

    Science.gov (United States)

    Villar, Margarita; Mateos-Hernandez, Lourdes; de la Fuente, Jose

    2018-03-14

    Why an autoimmune disease that is the main cause of the acute neuromuscular paralysis worldwide has not yet a well-characterized cause or an effective treatment? The existence of different clinical variants for the Guillain-Barré syndrome (GBS) coupled with the fact that a high number of pathogens can cause an infection that sometimes, but not always, precedes the development of the syndrome, confers a high degree of uncertainty for both prognosis and treatment. In the post-genomic era, the development of omics technologies for the high-throughput analysis of biological molecules is allowing the characterization of biological systems in a degree of depth unimaginable before. In this context, this work summarize the application of post-genomics technologies to the study of GBS. We performed a structured search of bibliographic databases for peer-reviewed research literature to outline the state of the art with regard the application of post-genomics technologies to the study of GBS. The quality of retrieved papers was assessed using standard tools and thirty-four were included in the review. To date, transcriptomics and proteomics have been the unique post-genomics approaches applied to GBS study. Most of these studies have been performed on cerebrospinal fluid samples and only few studies have been conducted with other samples such as serum, Schwann cells and human peripheral nerve. In the post-genomics era, transcriptomics and proteomics have shown the possibilities that omics technologies can offer for a better understanding of the immunological and pathological mechanisms involved in GBS and the identification of potential biomarkers, but these results have only shown the tip of the iceberg and there is still a long way to exploit the full potential that post-genomics approaches could offer to the study of the GBS. The integration of different omics datasets through a systems biology approach could allow network-based analyses to describe the complexity and

  13. Integrated Giant Magnetoresistance Technology for Approachable Weak Biomagnetic Signal Detections.

    Science.gov (United States)

    Shen, Hui-Min; Hu, Liang; Fu, Xin

    2018-01-07

    With the extensive applications of biomagnetic signals derived from active biological tissue in both clinical diagnoses and human-computer-interaction, there is an increasing need for approachable weak biomagnetic sensing technology. The inherent merits of giant magnetoresistance (GMR) and its high integration with multiple technologies makes it possible to detect weak biomagnetic signals with micron-sized, non-cooled and low-cost sensors, considering that the magnetic field intensity attenuates rapidly with distance. This paper focuses on the state-of-art in integrated GMR technology for approachable biomagnetic sensing from the perspective of discipline fusion between them. The progress in integrated GMR to overcome the challenges in weak biomagnetic signal detection towards high resolution portable applications is addressed. The various strategies for 1/ f noise reduction and sensitivity enhancement in integrated GMR technology for sub-pT biomagnetic signal recording are discussed. In this paper, we review the developments of integrated GMR technology for in vivo/vitro biomagnetic source imaging and demonstrate how integrated GMR can be utilized for biomagnetic field detection. Since the field sensitivity of integrated GMR technology is being pushed to fT/Hz 0.5 with the focused efforts, it is believed that the potential of integrated GMR technology will make it preferred choice in weak biomagnetic signal detection in the future.

  14. Functional Genomics Approaches to Studying Symbioses between Legumes and Nitrogen-Fixing Rhizobia.

    Science.gov (United States)

    Lardi, Martina; Pessi, Gabriella

    2018-05-18

    Biological nitrogen fixation gives legumes a pronounced growth advantage in nitrogen-deprived soils and is of considerable ecological and economic interest. In exchange for reduced atmospheric nitrogen, typically given to the plant in the form of amides or ureides, the legume provides nitrogen-fixing rhizobia with nutrients and highly specialised root structures called nodules. To elucidate the molecular basis underlying physiological adaptations on a genome-wide scale, functional genomics approaches, such as transcriptomics, proteomics, and metabolomics, have been used. This review presents an overview of the different functional genomics approaches that have been performed on rhizobial symbiosis, with a focus on studies investigating the molecular mechanisms used by the bacterial partner to interact with the legume. While rhizobia belonging to the alpha-proteobacterial group (alpha-rhizobia) have been well studied, few studies to date have investigated this process in beta-proteobacteria (beta-rhizobia).

  15. The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human Genome.

    Science.gov (United States)

    González-Prieto, Coral; Gabriel, Richard; Dehio, Christoph; Schmidt, Manfred; Llosa, Matxalen

    2017-06-15

    Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery. IMPORTANCE Different biotechnological applications, including gene therapy strategies, require permanent modification of target cells. Long-term expression is achieved either by extrachromosomal persistence or by integration of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC, a bacterial protein with site

  16. IVAG: An Integrative Visualization Application for Various Types of Genomic Data Based on R-Shiny and the Docker Platform.

    Science.gov (United States)

    Lee, Tae-Rim; Ahn, Jin Mo; Kim, Gyuhee; Kim, Sangsoo

    2017-12-01

    Next-generation sequencing (NGS) technology has become a trend in the genomics research area. There are many software programs and automated pipelines to analyze NGS data, which can ease the pain for traditional scientists who are not familiar with computer programming. However, downstream analyses, such as finding differentially expressed genes or visualizing linkage disequilibrium maps and genome-wide association study (GWAS) data, still remain a challenge. Here, we introduce a dockerized web application written in R using the Shiny platform to visualize pre-analyzed RNA sequencing and GWAS data. In addition, we have integrated a genome browser based on the JBrowse platform and an automated intermediate parsing process required for custom track construction, so that users can easily build and navigate their personal genome tracks with in-house datasets. This application will help scientists perform series of downstream analyses and obtain a more integrative understanding about various types of genomic data by interactively visualizing them with customizable options.

  17. A design approach for integrating thermoelectric devices using topology optimization

    DEFF Research Database (Denmark)

    Soprani, Stefano; Haertel, Jan Hendrik Klaas; Lazarov, Boyan Stefanov

    2016-01-01

    Efficient operation of thermoelectric devices strongly relies on the thermal integration into the energy conversion system in which they operate. Effective thermal integration reduces the temperature differences between the thermoelectric module and its thermal reservoirs, allowing the system...... to operate more efficiently. This work proposes and experimentally demonstrates a topology optimization approach as a design tool for efficient integration of thermoelectric modules into systems with specific design constraints. The approach allows thermal layout optimization of thermoelectric systems...... for different operating conditions and objective functions, such as temperature span, efficiency, and power recoveryrate. As a specific application, the integration of a thermoelectric cooler into the electronics section ofa downhole oil well intervention tool is investigated, with the objective of minimizing...

  18. Science Teachers’ Pedagogical Content Knowledge and Integrated Approach

    Science.gov (United States)

    Adi Putra, M. J.; Widodo, A.; Sopandi, W.

    2017-09-01

    The integrated approach refers to the stages of pupils’ psychological development. Unfortunately, the competences which are designed into the curriculum is not appropriate with the child development. This Manuscript presents PCK (pedagogical content knowledge) of teachers who teach science content utilizing an integrated approach. The data has been collected by using CoRe, PaP-eR, and interviews from six elementary teachers who teach science. The paper informs that high and stable teacher PCKs have an impact on how teachers present integrated teaching. Because it is influenced by the selection of important content that must be submitted to the students, the depth of the content, the reasons for choosing the teaching procedures and some other things. So for teachers to be able to integrate teaching, they should have a balanced PCK.

  19. BiologicalNetworks 2.0 - an integrative view of genome biology data

    Directory of Open Access Journals (Sweden)

    Ponomarenko Julia

    2010-12-01

    Full Text Available Abstract Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other and their relations (interactions, co-expression, co-citations, and other. The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org.

  20. 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.

  1. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Directory of Open Access Journals (Sweden)

    Hongbo Shi

    Full Text Available 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.

  2. A statistical framework to predict functional non-coding regions in the human genome through integrated analysis of annotation data.

    Science.gov (United States)

    Lu, Qiongshi; Hu, Yiming; Sun, Jiehuan; Cheng, Yuwei; Cheung, Kei-Hoi; Zhao, Hongyu

    2015-05-27

    Identifying functional regions in the human genome is a major goal in human genetics. Great efforts have been made to functionally annotate the human genome either through computational predictions, such as genomic conservation, or high-throughput experiments, such as the ENCODE project. These efforts have resulted in a rich collection of functional annotation data of diverse types that need to be jointly analyzed for integrated interpretation and annotation. Here we present GenoCanyon, a whole-genome annotation method that performs unsupervised statistical learning using 22 computational and experimental annotations thereby inferring the functional potential of each position in the human genome. With GenoCanyon, we are able to predict many of the known functional regions. The ability of predicting functional regions as well as its generalizable statistical framework makes GenoCanyon a unique and powerful tool for whole-genome annotation. The GenoCanyon web server is available at http://genocanyon.med.yale.edu.

  3. Selective Gene Delivery for Integrating Exogenous DNA into Plastid and Mitochondrial Genomes Using Peptide-DNA Complexes.

    Science.gov (United States)

    Yoshizumi, Takeshi; Oikawa, Kazusato; Chuah, Jo-Ann; Kodama, Yutaka; Numata, Keiji

    2018-05-14

    Selective gene delivery into organellar genomes (mitochondrial and plastid genomes) has been limited because of a lack of appropriate platform technology, even though these organelles are essential for metabolite and energy production. Techniques for selective organellar modification are needed to functionally improve organelles and produce transplastomic/transmitochondrial plants. However, no method for mitochondrial genome modification has yet been established for multicellular organisms including plants. Likewise, modification of plastid genomes has been limited to a few plant species and algae. In the present study, we developed ionic complexes of fusion peptides containing organellar targeting signal and plasmid DNA for selective delivery of exogenous DNA into the plastid and mitochondrial genomes of intact plants. This is the first report of exogenous DNA being integrated into the mitochondrial genomes of not only plants, but also multicellular organisms in general. This fusion peptide-mediated gene delivery system is a breakthrough platform for both plant organellar biotechnology and gene therapy for mitochondrial diseases in animals.

  4. 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.

  5. Integrating Nonadditive Genomic Relationship Matrices into the Study of Genetic Architecture of Complex Traits.

    Science.gov (United States)

    Nazarian, Alireza; Gezan, Salvador A

    2016-03-01

    The study of genetic architecture of complex traits has been dramatically influenced by implementing genome-wide analytical approaches during recent years. Of particular interest are genomic prediction strategies which make use of genomic information for predicting phenotypic responses instead of detecting trait-associated loci. In this work, we present the results of a simulation study to improve our understanding of the statistical properties of estimation of genetic variance components of complex traits, and of additive, dominance, and genetic effects through best linear unbiased prediction methodology. Simulated dense marker information was used to construct genomic additive and dominance matrices, and multiple alternative pedigree- and marker-based models were compared to determine if including a dominance term into the analysis may improve the genetic analysis of complex traits. Our results showed that a model containing a pedigree- or marker-based additive relationship matrix along with a pedigree-based dominance matrix provided the best partitioning of genetic variance into its components, especially when some degree of true dominance effects was expected to exist. Also, we noted that the use of a marker-based additive relationship matrix along with a pedigree-based dominance matrix had the best performance in terms of accuracy of correlations between true and estimated additive, dominance, and genetic effects. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Genome-Wide Analysis of Transposon and Retroviral Insertions Reveals Preferential Integrations in Regions of DNA Flexibility.

    Science.gov (United States)

    Vrljicak, Pavle; Tao, Shijie; Varshney, Gaurav K; Quach, Helen Ngoc Bao; Joshi, Adita; LaFave, Matthew C; Burgess, Shawn M; Sampath, Karuna

    2016-04-07

    DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germ-line transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence the integration of heterologous DNA in genomes, and have implications for targeted genome engineering. Copyright © 2016 Vrljicak et al.

  7. Two heuristic approaches to describe periodicities in genomic microarrays

    Directory of Open Access Journals (Sweden)

    Jörg Aßmus

    2009-09-01

    Full Text Available In the first part we discuss the filtering of panels of time series based on singular value decomposition. The discussion is based on an approach where this filtering is used to normalize microarray data. We point out effects on the periodicity and phases for time series panels. In the second part we investigate time dependent periodic panels with different phases. We align the time series in the panel and discuss the periodogram of the aligned time series with the purpose of describing the periodic structure of the panel. The method is quite powerful assuming known phases in the model, but it deteriorates rapidly for noisy data.  

  8. An integrated lean-methods approach to hospital facilities redesign.

    Science.gov (United States)

    Nicholas, John

    2012-01-01

    Lean production methods for eliminating waste and improving processes in manufacturing are now being applied in healthcare. As the author shows, the methods are appropriate for redesigning hospital facilities. When used in an integrated manner and employing teams of mostly clinicians, the methods produce facility designs that are custom-fit to patient needs and caregiver work processes, and reduce operational costs. The author reviews lean methods and an approach for integrating them in the redesign of hospital facilities. A case example of the redesign of an emergency department shows the feasibility and benefits of the approach.

  9. A Key Event Path Analysis Approach for Integrated Systems

    Directory of Open Access Journals (Sweden)

    Jingjing Liao

    2012-01-01

    Full Text Available By studying the key event paths of probabilistic event structure graphs (PESGs, a key event path analysis approach for integrated system models is proposed. According to translation rules concluded from integrated system architecture descriptions, the corresponding PESGs are constructed from the colored Petri Net (CPN models. Then the definitions of cycle event paths, sequence event paths, and key event paths are given. Whereafter based on the statistic results after the simulation of CPN models, key event paths are found out by the sensitive analysis approach. This approach focuses on the logic structures of CPN models, which is reliable and could be the basis of structured analysis for discrete event systems. An example of radar model is given to characterize the application of this approach, and the results are worthy of trust.

  10. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach.

    Science.gov (United States)

    Greub, Gilbert; Kebbi-Beghdadi, Carole; Bertelli, Claire; Collyn, François; Riederer, Beat M; Yersin, Camille; Croxatto, Antony; Raoult, Didier

    2009-12-23

    With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.

  11. Functional Genomic Approaches for the Study of Fetal/Placental Development in Swine with Special Emphasis on Imprinted Genes

    Science.gov (United States)

    The overall focus of this chapter will be the application of functional genomic approaches for the study of the imprinted gene family in swine. While there are varied definitions of “functional genomics” in general they focus on the application of genomic approaches such as DNA microarrays, single n...

  12. Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics.

    Science.gov (United States)

    Maldonado, Elaina M; Leoncikas, Vytautas; Fisher, Ciarán P; Moore, J Bernadette; Plant, Nick J; Kierzek, Andrzej M

    2017-11-01

    The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  13. GENOMIC APPROACHES FOR IMPROVEMENT OF DROUGHT ADAPTATION IN WHEAT

    Directory of Open Access Journals (Sweden)

    Dénes Dudits

    2008-09-01

    Full Text Available Breeding for yield stability under water limited conditions plays an essential role in the reduction of economic and social consequences of global climate changes. We show that two exotic drought resistant genotypes (Kobomughi and Plainsmann differ in root growth rate, root/shoot ratio, and adaptation to low soil water content. These genotypes exhibit characteristic transcript profiles as shown by barley macroarray studies using 10500 unigenes. Reprogramming of gene expression primarily occurred during the 1-2 weeks of water stress, and 6,1% of tested genes were up-regulated in roots of the more adaptive Plainsmann plants. The time course for expression of gene clusters from Kobomughi genotype revealed a prompt and transient gene activation that can help the survival of plants through function of various defense mechanisms. The aldo-keto reductases (AKRs can detoxify lipid peroxidation products (4-hydroxynon-2-enal and glycolysis-derived reactive aldehydes (metylglyoxal that contribute significantly to cellular damages caused by variety of environmental stresses such as drought, high light intensity, UV-B irradiation, cold. Overproduction of AKRs in transgenic tobacco or wheat plants provides considerable stress tolerance and resistance to methylglyoxal. Several transgenic wheat genotypes have been produced with production of elevated level of AKR enzyme. The drought tolerance of these materials was tested by a complex stress diagnostic system, that integrates imaging of plants and monitoring the leaf temperature and fluorescence induction. Based on these parameters, we can conclude that this transgenic strategy that is based on detoxification of lipid aldehyde can result in improved stress adaptation and reduced yield loss.

  14. The Human Genome Project and the social contract: a law policy approach.

    Science.gov (United States)

    Byk, C

    1992-08-01

    For the first time in history, genetics will enable science to completely identify each human as genetically unique. Will this knowledge reinforce the trend for more individual liberties or will it create a 'brave new world'? A law policy approach to the problems raised by the human genome project shows how far our democratic institutions are from being the proper forum to discuss such issues. Because of the fears and anxiety raised in the population, and also because of its wide implications on the everyday life, the human genome analysis more than any other project needs to succeed in setting up such a social assessment.

  15. Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization.

    Directory of Open Access Journals (Sweden)

    Xiaoquan Wen

    2017-03-01

    Full Text Available We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the association data. Using this utility, we further illustrate the importance of enrichment analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative.

  16. Chemical Approach to Biological Safety: Molecular-Level Control of an Integrated Zinc Finger Nuclease

    DEFF Research Database (Denmark)

    Németh, Eszter; Asaka, Masamitsu N; Kato, Kohsuke

    2018-01-01

    circular dichroism spectroscopy, and nano-electrospray ionisation mass spectrometry. In situ intramolecular activation of the nuclease domain was observed, resulting in specific cleavage of DNA with moderate activity. This study represents a new approach to AN design through integrated nucleases consisting......Application of artificial nucleases (ANs) in genome editing is still hindered by their cytotoxicity related to off-target cleavages. This problem can be targeted by regulation of the nuclease domain. Here, we provide an experimental survey of computationally designed integrated zinc finger...... nucleases, constructed by linking the inactivated catalytic centre and the allosteric activator sequence of the colicin E7 nuclease domain to the two opposite termini of a zinc finger array. DNA specificity and metal binding were confirmed by electrophoretic mobility shift assays, synchrotron radiation...

  17. Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era.

    Science.gov (United States)

    Chiu, Weihsueh A; Euling, Susan Y; Scott, Cheryl Siegel; Subramaniam, Ravi P

    2013-09-15

    The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA)--i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence--using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes. Published by Elsevier Inc.

  18. Integrated Approaches to Occupational Health and Safety: A Systematic Review.

    Science.gov (United States)

    Cooklin, A; Joss, N; Husser, E; Oldenburg, B

    2017-09-01

    The study objective was to conduct a systematic review of the effectiveness of integrated workplace interventions that combine health promotion with occupational health and safety. Electronic databases (n = 8), including PsychInfo and MEDLINE, were systematically searched. Studies included were those that reported on workplace interventions that met the consensus definition of an "integrated approach," published in English, in the scientific literature since 1990. Data extracted were occupation, worksite, country, sample size, intervention targets, follow-up period, and results reported. Quality was assessed according to American College of Occupational and Environmental Medicine Practice Guidelines. Heterogeneity precluded formal meta-analyses. Results were classified according to the outcome(s) assessed into five categories (health promotion, injury prevention, occupational health and safety management, psychosocial, and return-on-investment). Narrative synthesis of outcomes was performed. A total of 31 eligible studies were identified; 23 (74%) were (quasi-)experimental trials. Effective interventions were most of those aimed at improving employee physical or mental health. Less consistent results were reported from integrated interventions targeting occupational health and safety management, injury prevention, or organizational cost savings. Integrated approaches have been posed as comprehensive solutions to complex issues. Empirical evidence, while still emerging, provides some support for this. Continuing investment in, and evaluation of, integrated approaches are worthwhile.

  19. Safety Concepts in Structural Glass Engineering : Towards an Integrated Approach

    NARCIS (Netherlands)

    Bos, F.P.

    2009-01-01

    This dissertation proposes the Integrated Approach to Structural Glass Safety, based on four clearly defined element safety properties, damage sensitivity, relative resistance, redundancy, and fracture mode. The Element Safety Diagram (ESD) is introduced to provide an easy-to-read graphical

  20. Towards an integrated approach in supporting microbiological food safety decisions

    DEFF Research Database (Denmark)

    Havelaar, A.H.; Braunig, J.; Christiansen, K.

    2007-01-01

    an integrated scientific approach combining veterinary and medical epidemiology, risk assessment for the farm-to-fork food chain as well as agricultural and health economy. Scientific advice is relevant in all stages of the policy cycle: to assess the magnitude of the food safety problem, to define...

  1. Recent changes in Central European landscapes: An integrative ecological approach

    Czech Academy of Sciences Publication Activity Database

    Těšitel, Jan; Kučera, Tomáš

    2005-01-01

    Roč. 24, č. 1 (2005), s. 3-6 ISSN 1335-342X Institutional research plan: CEZ:AV0Z60870520 Keywords : integrative ecological approach * transdisciplinarity * interdisciplinarity * landscape ecology Subject RIV: DO - Wilderness Conservation Impact factor: 0.085, year: 2005

  2. Child Psychotherapy, Child Analysis, and Medication: A Flexible, Integrative Approach.

    Science.gov (United States)

    Whitman, Laura

    2015-01-01

    For children with moderate to severe emotional or behavioral problems, the current approach in child psychiatry is to make an assessment for the use of both psychotherapy and medication. This paper describes integration of antidepressants and stimulants with psychoanalytically oriented techniques.

  3. An Integrated Approach to Indoor and Outdoor Localization

    Science.gov (United States)

    2017-04-17

    TITLE AND SUBTITLE An Integrated Approach to Indoor and Outdoor Localization 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-12-1-0299 5c.   PROGRAM ELEMENT...Distribution approved for public release. Figure 5: A flowchart of the method of computing an initial position estimate by comparing a single WiFi scan

  4. 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

  5. Availability objectives integration to design. The CIDEM approach

    International Nuclear Information System (INIS)

    Degrave, C.; Martin-Onraet, M.

    1994-01-01

    Considering the operation experience feedback from its nuclear park and from foreign parks, and considering new approaches and design tools such as concurrent engineering, total quality, etc., EDF (Electricite de France) has decided to start the CIDEM approach (integration of availability, operating experience feedback and maintenance into design), an analytical and systematical study process for new projects (REP2000 (or PWR2000)), in order to optimize as much as possible the design phase while integrating maintenance, availability and safety objectives, with the view of a minimized kWh cost. This process, already used in other industries, employs concepts such as RAM (Reliability Availability Maintainability), RCM (Reliability Centered Maintenance) and ILS (Integrated Logistic Support). The availability and maintenance scheduling studies for the REP2000 project are detailed. 10 fig., 6 tab

  6. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health.

    Science.gov (United States)

    Wood, Michael L; Royle, Nicola J

    2017-07-12

    Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease.

  7. Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis.

    Directory of Open Access Journals (Sweden)

    Rachael Natrajan

    2016-02-01

    Full Text Available The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters.We developed a quantitative measure of microenvironmental heterogeneity along three spatial dimensions (3-D in solid tumors, termed the tumor ecosystem diversity index (EDI, using fully automated histology image analysis coupled with statistical measures commonly used in ecology. This measure was compared with disease-specific survival, key mutations, genome-wide copy number, and expression profiling data in a retrospective study of 510 breast cancer patients as a test set and 516 breast cancer patients as an independent validation set. In high-grade (grade 3 breast cancers, we uncovered a striking link between high microenvironmental heterogeneity measured by EDI and a poor prognosis that cannot be explained by tumor size, genomics, or any other data types. However, this association was not observed in low-grade (grade 1 and 2 breast cancers. The prognostic value of EDI was superior to known prognostic factors and was enhanced with the addition of TP53 mutation status (multivariate analysis test set, p = 9 × 10-4, hazard ratio = 1.47, 95% CI 1.17-1.84; validation set, p = 0.0011, hazard ratio = 1.78, 95% CI 1.26-2.52. Integration with genome-wide profiling data identified losses of specific genes on 4p14 and 5q13 that were enriched in grade 3 tumors with high microenvironmental diversity that also substratified patients into poor prognostic groups. Limitations of this study include the number of cell types included in the model, that EDI has prognostic value only in grade 3 tumors, and that our spatial heterogeneity measure was dependent on spatial scale and tumor size.To our knowledge, this is the first

  8. Integrating radiology vertically into an undergraduate medical education curriculum: a triphasic integration approach

    Directory of Open Access Journals (Sweden)

    Al Qahtani F

    2014-06-01

    Full Text Available Fahd Al Qahtani,1 Adel Abdelaziz2,31Radiology Department, Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia; 2Medical Education Development Unit, Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia; 3Medical Education Department, Faculty of Medicine, Suez Canal University, Ismailia, EgyptAbstract: Fulfilling the goal of integrating radiology into undergraduate medical curricula is a real challenge due to the enduring faith assuming that traditional medical disciplines are worthy of consuming the available study time. In this manner, radiology is addressed occasionally and with relevance to these traditional disciplines. In Al-Baha University Faculty of Medicine, Al-Baha, Saudi Arabia, efforts have been made to integrate radiology vertically and in a structured manner into the undergraduate curriculum from the first year to the sixth year. For achieving convenient integration of radiology, a triphasic approach to integration is adopted. This approach consists of the integration of radiology foundations into the basic sciences phase, development of a distinct 4-week module in year 4, and finally, integration of clinical applications of radiology in the clinical phase modules. Feedback of students and inferences obtained through assessment and program evaluation are in favor of this approach to integration. Minor reform and some improvement related to time allocated and content balancing are still indicated.Keywords: radiology foundations, radiology module, students assessment

  9. Polymorphic integrations of an endogenous gammaretrovirus in the mule deer genome.

    Science.gov (United States)

    Elleder, Daniel; Kim, Oekyung; Padhi, Abinash; Bankert, Jason G; Simeonov, Ivan; Schuster, Stephan C; Wittekindt, Nicola E; Motameny, Susanne; Poss, Mary

    2012-03-01

    Endogenous retroviruses constitute a significant genomic fraction in all mammalian species. Typically they are evolutionarily old and fixed in the host species population. Here we report on a novel endogenous gammaretrovirus (CrERVγ; for cervid endogenous gammaretrovirus) in the mule deer (Odocoileus hemionus) that is insertionally polymorphic among individuals from the same geographical location, suggesting that it has a more recent evolutionary origin. Using PCR-based methods, we identified seven CrERVγ proviruses and demonstrated that they show various levels of insertional polymorphism in mule deer individuals. One CrERVγ provirus was detected in all mule deer sampled but was absent from white-tailed deer, indicating that this virus originally integrated after the split of the two species, which occurred approximately one million years ago. There are, on average, 100 CrERVγ copies in the mule deer genome based on quantitative PCR analysis. A CrERVγ provirus was sequenced and contained intact open reading frames (ORFs) for three virus genes. Transcripts were identified covering the entire provirus. CrERVγ forms a distinct branch of the gammaretrovirus phylogeny, with the closest relatives of CrERVγ being endogenous gammaretroviruses from sheep and pig. We demonstrated that white-tailed deer (Odocoileus virginianus) and elk (Cervus canadensis) DNA contain proviruses that are closely related to mule deer CrERVγ in a conserved region of pol; more distantly related sequences can be identified in the genome of another member of the Cervidae, the muntjac (Muntiacus muntjak). The discovery of a novel transcriptionally active and insertionally polymorphic retrovirus in mammals could provide a useful model system to study the dynamic interaction between the host genome and an invading retrovirus.

  10. DNA double-strand break response in stem cells: mechanisms to maintain genomic integrity.

    Science.gov (United States)

    Nagaria, Pratik; Robert, Carine; Rassool, Feyruz V

    2013-02-01

    Embryonic stem cells (ESCs) represent the point of origin of all cells in a given organism and must protect their genomes from both endogenous and exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most lethal forms of damage, and failure to adequately repair DSBs would not only compromise the ability of SCs to self-renew and differentiate, but will also lead to genomic instability and disease. Herein, we describe the mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen species (ROS) and ionizing radiation, compared to somatic cells. We will also discuss whether the DSB response is fully reprogrammed in induced pluripotent stem cells (iPSCs) and the role of the DNA damage response (DDR) in the reprogramming of these cells. ESCs have distinct mechanisms to protect themselves against DSBs and oxidative stress compared to somatic cells. The response to damage and stress is crucial for the maintenance of self-renewal and differentiation capacity in SCs. iPSCs appear to reprogram some of the responses to genotoxic stress. However, it remains to be determined if iPSCs also retain some DDR characteristics of the somatic cells of origin. The mechanisms regulating the genomic integrity in ESCs and iPSCs are critical for its safe use in regenerative medicine and may shed light on the pathways and factors that maintain genomic stability, preventing diseases such as cancer. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. BAUM: Improving genome assembly by adaptive unique mapping and local overlap-layout-consensus approach.

    Science.gov (United States)

    Wang, Anqi; Wang, Zhanyu; Li, Zheng; Li, Lei M

    2018-01-15

    It is highly desirable to assemble genomes of high continuity and consistency at low cost. The current bottleneck of draft genome continuity using the Second Generation Sequencing (SGS) reads is primarily caused by uncertainty among repetitive sequences. Even though the Single-Molecule Real-Time sequencing technology is very promising to overcome the uncertainty issue, its relatively high cost and error rate add burden on budget or computation. Many long-read assemblers take the overlap-layout-consensus (OLC) paradigm, which is less sensitive to sequencing errors, heterozygosity and variability of coverage. However, current assemblers of SGS data do not sufficiently take advantage of the OLC approach. Aiming at minimizing uncertainty, the proposed method BAUM, breaks the whole genome into regions by adaptive unique mapping; then the local OLC is used to assemble each region in parallel. BAUM can: (1) perform reference-assisted assembly based on the genome of a close species; (2) or improve the results of existing assemblies that are obtained based on short or long sequencing reads. The tests on two eukaryote genomes, a wild rice Oryza longistaminata and a parrot Melopsittacus undulatus, show that BAUM achieved substantial improvement on genome size and continuity. Besides, BAUM reconstructed a considerable amount of repetitive regions that failed to be assembled by existing short read assemblers. We also propose statistical approaches to control the uncertainty in different steps of BAUM. http://www.zhanyuwang.xin/wordpress/index.php/2017/07/21/baum. lilei@amss.ac.cn. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  12. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

    Science.gov (United States)

    Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-03-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. Critical perspectives of pedagogical approaches to reversing the order of integration in double integrals

    Science.gov (United States)

    Tisdell, Christopher C.

    2017-11-01

    This paper presents some critical perspectives regarding pedagogical approaches to the method of reversing the order of integration in double integrals from prevailing educational literature on multivariable calculus. First, we question the message found in popular textbooks that the traditional process of reversing the order of integration is necessary when solving well-known problems. Second, we illustrate that the method of integration by parts can be directly applied to many of the classic pedagogical problems in the literature concerning double integrals, without taking the well-worn steps associated with reversing the order of integration. Third, we examine the benefits and limitations of such a method. In our conclusion, we advocate for integration by parts to be a part of the pedagogical conversation in the learning and teaching of double integral methods; and call for more debate around its use in the learning and teaching of other areas of mathematics. Finally, we emphasize the need for critical approaches in the pedagogy of mathematics more broadly.

  14. Science of Integrated Approaches to Natural Resources Management

    Science.gov (United States)

    Tengberg, Anna; Valencia, Sandra

    2017-04-01

    To meet multiple environmental objectives, integrated programming is becoming increasingly important for the Global Environmental Facility (GEF), the financial mechanism of the multilateral environmental agreements, including the United Nations Convention to Combat Desertification (UNCCD). Integration of multiple environmental, social and economic objectives also contributes to the achievement of the Sustainable Development Goals (SDGs) in a timely and cost-effective way. However, integration is often not well defined. This paper therefore focuses on identifying key aspects of integration and assessing their implementation in natural resources management (NRM) projects. To that end, we draw on systems thinking literature, and carry out an analysis of a random sample of GEF integrated projects and in-depth case studies demonstrating lessons learned and good practices in addressing land degradation and other NRM challenges. We identify numerous challenges and opportunities of integrated approaches that need to be addressed in order to maximise the catalytic impact of the GEF during problem diagnosis, project design, implementation and governance. We highlight the need for projects to identify clearer system boundaries and main feedback mechanisms within those boundaries, in order to effectively address drivers of environmental change. We propose a theory of change for Integrated Natural Resources Management (INRM) projects, where short-term environmental and socio-economic benefits will first accrue at the local level. Implementation of improved INRM technologies and practices at the local level can be extended through spatial planning, strengthening of innovation systems, and financing and incentive mechanisms at the watershed and/or landscape/seascape level to sustain and enhance ecosystem services at larger scales and longer time spans. We conclude that the evolving scientific understanding of factors influencing social, technical and institutional innovations and

  15. Computational Approaches for Integrative Analysis of the Metabolome and Microbiome

    Directory of Open Access Journals (Sweden)

    Jasmine Chong

    2017-11-01

    Full Text Available The study of the microbiome, the totality of all microbes inhabiting the host or an environmental niche, has experienced exponential growth over the past few years. The microbiome contributes functional genes and metabolites, and is an important factor for maintaining health. In this context, metabolomics is increasingly applied to complement sequencing-based approaches (marker genes or shotgun metagenomics to enable resolution of microbiome-conferred functionalities associated with health. However, analyzing the resulting multi-omics data remains a significant challenge in current microbiome studies. In this review, we provide an overview of different computational approaches that have been used in recent years for integrative analysis of metabolome and microbiome data, ranging from statistical correlation analysis to metabolic network-based modeling approaches. Throughout the process, we strive to present a unified conceptual framework for multi-omics integration and interpretation, as well as point out potential future directions.

  16. Integrated systems approach to meet the insider threat

    International Nuclear Information System (INIS)

    Barnes, L.D.

    1985-01-01

    This paper describes an approach to mitigating the insider threat by integrating and supplementing existing data systems and procedures without placing an undue burden on plant management and operating personnel. Nuclear facilities have plans to deal with any forseeable chain of events, and long-term records of activities are maintained to verify that the requirements are met. The integrated systems approach proposed in this paper does not change established facility practices; rather, the approach attempts to utilize the information generated by the system. This will provide real-time interaction between the documented work permits, the operating procedure system, and the security system so that controlled access authorizations are based on a need to enter and access is limited to specific times and places

  17. Inter-replicon Gene Flow Contributes to Transcriptional Integration in the Sinorhizobium meliloti Multipartite Genome

    Directory of Open Access Journals (Sweden)

    George C. diCenzo

    2018-05-01

    Full Text Available Integration of newly acquired genes into existing regulatory networks is necessary for successful horizontal gene transfer (HGT. Ten percent of bacterial species contain at least two DNA replicons over 300 kilobases in size, with the secondary replicons derived predominately through HGT. The Sinorhizobium meliloti genome is split between a 3.7 Mb chromosome, a 1.7 Mb chromid consisting largely of genes acquired through ancient HGT, and a 1.4 Mb megaplasmid consisting primarily of recently acquired genes. Here, RNA-sequencing is used to examine the transcriptional consequences of massive, synthetic genome reduction produced through the removal of the megaplasmid and/or the chromid. Removal of the pSymA megaplasmid influenced the transcription of only six genes. In contrast, removal of the chromid influenced expression of ∼8% of chromosomal genes and ∼4% of megaplasmid genes. This was mediated in part by the loss of the ETR DNA region whose presence on pSymB is due to a translocation from the chromosome. No obvious functional bias among the up-regulated genes was detected, although genes with putative homologs on the chromid were enriched. Down-regulated genes were enriched in motility and sensory transduction pathways. Four transcripts were examined further, and in each case the transcriptional change could be traced to loss of specific pSymB regions. In particularly, a chromosomal transporter was induced due to deletion of bdhA likely mediated through 3-hydroxybutyrate accumulation. These data provide new insights into the evolution of the multipartite bacterial genome, and more generally into the integration of horizontally acquired genes into the transcriptome.

  18. Inter-replicon Gene Flow Contributes to Transcriptional Integration in the Sinorhizobium meliloti Multipartite Genome.

    Science.gov (United States)

    diCenzo, George C; Wellappili, Deelaka; Golding, G Brian; Finan, Turlough M

    2018-05-04

    Integration of newly acquired genes into existing regulatory networks is necessary for successful horizontal gene transfer (HGT). Ten percent of bacterial species contain at least two DNA replicons over 300 kilobases in size, with the secondary replicons derived predominately through HGT. The Sinorhizobium meliloti genome is split between a 3.7 Mb chromosome, a 1.7 Mb chromid consisting largely of genes acquired through ancient HGT, and a 1.4 Mb megaplasmid consisting primarily of recently acquired genes. Here, RNA-sequencing is used to examine the transcriptional consequences of massive, synthetic genome reduction produced through the removal of the megaplasmid and/or the chromid. Removal of the pSymA megaplasmid influenced the transcription of only six genes. In contrast, removal of the chromid influenced expression of ∼8% of chromosomal genes and ∼4% of megaplasmid genes. This was mediated in part by the loss of the ETR DNA region whose presence on pSymB is due to a translocation from the chromosome. No obvious functional bias among the up-regulated genes was detected, although genes with putative homologs on the chromid were enriched. Down-regulated genes were enriched in motility and sensory transduction pathways. Four transcripts were examined further, and in each case the transcriptional change could be traced to loss of specific pSymB regions. In particularly, a chromosomal transporter was induced due to deletion of bdhA likely mediated through 3-hydroxybutyrate accumulation. These data provide new insights into the evolution of the multipartite bacterial genome, and more generally into the integration of horizontally acquired genes into the transcriptome. Copyright © 2018 diCenzo, et al.

  19. 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

    2015-03-01

    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. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Integrated genomic and interfacility patient-transfer data reveal the transmission pathways of multidrug-resistant Klebsiella pneumoniae in a regional outbreak.

    Science.gov (United States)

    Snitkin, Evan S; Won, Sarah; Pirani, Ali; Lapp, Zena; Weinstein, Robert A; Lolans, Karen; Hayden, Mary K

    2017-11-22

    Development of effective strategies to limit the proliferation of multidrug-resistant organisms requires a thorough understanding of how such organisms spread among health care facilities. We sought to uncover the chains of transmission underlying a 2008 U.S. regional outbreak of carbapenem-resistant Klebsiella pneumoniae by performing an integrated analysis of genomic and interfacility patient-transfer data. Genomic analysis yielded a high-resolution transmission network that assigned directionality to regional transmission events and discriminated between intra- and interfacility transmission when epidemiologic data were ambiguous or misleading. Examining the genomic transmission network in the context of interfacility patient transfers (patient-sharing networks) supported the role of patient transfers in driving the outbreak, with genomic analysis revealing that a small subset of patient-transfer events was sufficient to explain regional spread. Further integration of the genomic and patient-sharing networks identified one nursing home as an important bridge facility early in the outbreak-a role that was not apparent from analysis of genomic or patient-transfer data alone. Last, we found that when simulating a real-time regional outbreak, our methodology was able to accurately infer the facility at which patients acquired their infections. This approach has the potential to identify facilities with high rates of intra- or interfacility transmission, data that will be useful for triggering targeted interventions to prevent further spread of multidrug-resistant organisms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. MIPS Arabidopsis thaliana Database (MAtDB): an integrated biological knowledge resource based on the first complete plant genome

    Science.gov (United States)

    Schoof, Heiko; Zaccaria, Paolo; Gundlach, Heidrun; Lemcke, Kai; Rudd, Stephen; Kolesov, Grigory; Arnold, Roland; Mewes, H. W.; Mayer, Klaus F. X.

    2002-01-01

    Arabidopsis thaliana is the first plant for which the complete genome has been sequenced and published. Annotation of complex eukaryotic genomes requires more than the assignment of genetic elements to the sequence. Besides completing the list of genes, we need to discover their cellular roles, their regulation and their interactions in order to understand the workings of the whole plant. The MIPS Arabidopsis thaliana Database (MAtDB; http://mips.gsf.de/proj/thal/db) started out as a repository for genome sequence data in the European Scientists Sequencing Arabidopsis (ESSA) project and the Arabidopsis Genome Initiative. Our aim is to transform MAtDB into an integrated biological knowledge resource by integrating diverse data, tools, query and visualization capabilities and by creating a comprehensive resource for Arabidopsis as a reference model for other species, including crop plants. PMID:11752263

  2. Posterior Approach to Kidney Dissection: An Old Surgical Approach for Integrated Medical Curricula

    Science.gov (United States)

    Daly, Frank J.; Bolender, David L.; Jain, Deepali; Uyeda, Sheryl; Hoagland, Todd M.

    2015-01-01

    Integrated medical curricular changes are altering the historical regional anatomy approach to abdominal dissection. The renal system is linked physiologically and biochemically to the cardiovascular and respiratory systems; yet, anatomists often approach the urinary system as part of the abdomen and pelvic regions. As part of an integrated…

  3. Integrating Crop Growth Models with Whole Genome Prediction through Approximate Bayesian Computation.

    Directory of Open Access Journals (Sweden)

    Frank Technow

    Full Text Available Genomic selection, enabled by whole genome prediction (WGP methods, is revolutionizing plant breeding. Existing WGP methods have been shown to deliver accurate predictions in the most common settings, such as prediction of across environment performance for traits with additive gene effects. However, prediction of traits with non-additive gene effects and prediction of genotype by environment interaction (G×E, continues to be challenging. Previous attempts to increase prediction accuracy for these particularly difficult tasks employed prediction methods that are purely statistical in nature. Augmenting the statistical methods with biological knowledge has been largely overlooked thus far. Crop growth models (CGMs attempt to represent the impact of functional relationships between plant physiology and the environment in the formation of yield and similar output traits of interest. Thus, they can explain the impact of G×E and certain types of non-additive gene effects on the expressed phenotype. Approximate Bayesian computation (ABC, a novel and powerful computational procedure, allows the incorporation of CGMs directly into the estimation of whole genome marker effects in WGP. Here we provide a proof of concept study for this novel approach and demonstrate its use with synthetic data sets. We show that this novel approach can be considerably more accurate than the benchmark WGP method GBLUP in predicting performance in environments represented in the estimation set as well as in previously unobserved environments for traits determined by non-additive gene effects. We conclude that this proof of concept demonstrates that using ABC for incorporating biological knowledge in the form of CGMs into WGP is a very promising and novel approach to improving prediction accuracy for some of the most challenging scenarios in plant breeding and applied genetics.

  4. Spatial Data Integration Using Ontology-Based Approach

    Science.gov (United States)

    Hasani, S.; Sadeghi-Niaraki, A.; Jelokhani-Niaraki, M.

    2015-12-01

    In today's world, the necessity for spatial data for various organizations is becoming so crucial that many of these organizations have begun to produce spatial data for that purpose. In some circumstances, the need to obtain real time integrated data requires sustainable mechanism to process real-time integration. Case in point, the disater management situations that requires obtaining real time data from various sources of information. One of the problematic challenges in the mentioned situation is the high degree of heterogeneity between different organizations data. To solve this issue, we introduce an ontology-based method to provide sharing and integration capabilities for the existing databases. In addition to resolving semantic heterogeneity, better access to information is also provided by our proposed method. Our approach is consisted of three steps, the first step is identification of the object in a relational database, then the semantic relationships between them are modelled and subsequently, the ontology of each database is created. In a second step, the relative ontology will be inserted into the database and the relationship of each class of ontology will be inserted into the new created column in database tables. Last step is consisted of a platform based on service-oriented architecture, which allows integration of data. This is done by using the concept of ontology mapping. The proposed approach, in addition to being fast and low cost, makes the process of data integration easy and the data remains unchanged and thus takes advantage of the legacy application provided.

  5. SPATIAL DATA INTEGRATION USING ONTOLOGY-BASED APPROACH

    Directory of Open Access Journals (Sweden)

    S. Hasani

    2015-12-01

    Full Text Available In today's world, the necessity for spatial data for various organizations is becoming so crucial that many of these organizations have begun to produce spatial data for that purpose. In some circumstances, the need to obtain real time integrated data requires sustainable mechanism to process real-time integration. Case in point, the disater management situations that requires obtaining real time data from various sources of information. One of the problematic challenges in the mentioned situation is the high degree of heterogeneity between different organizations data. To solve this issue, we introduce an ontology-based method to provide sharing and integration capabilities for the existing databases. In addition to resolving semantic heterogeneity, better access to information is also provided by our proposed method. Our approach is consisted of three steps, the first step is identification of the object in a relational database, then the semantic relationships between them are modelled and subsequently, the ontology of each database is created. In a second step, the relative ontology will be inserted into the database and the relationship of each class of ontology will be inserted into the new created column in database tables. Last step is consisted of a platform based on service-oriented architecture, which allows integration of data. This is done by using the concept of ontology mapping. The proposed approach, in addition to being fast and low cost, makes the process of data integration easy and the data remains unchanged and thus takes advantage of the legacy application provided.

  6. The Next Generation Precision Medical Record - A Framework for Integrating Genomes and Wearable Sensors with Medical Records

    OpenAIRE

    Batra, Prag; Singh, Enakshi; Bog, Anja; Wright, Mark; Ashley, Euan; Waggott, Daryl

    2016-01-01

    Current medical records are rigid with regards to emerging big biomedical data. Examples of poorly integrated big data that already exist in clinical practice include whole genome sequencing and wearable sensors for real time monitoring. Genome sequencing enables conventional diagnostic interrogation and forms the fundamental baseline for precision health throughout a patients lifetime. Mobile sensors enable tailored monitoring regimes for both reducing risk through precision health intervent...

  7. Network analysis of epidermal growth factor signaling using integrated genomic, proteomic and phosphorylation data.

    Directory of Open Access Journals (Sweden)

    Katrina M Waters

    Full Text Available To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  8. Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Liu, Tao; Quesenberry, Ryan D.; Willse, Alan R.; Bandyopadhyay, Somnath; Kathmann, Loel E.; Weber, Thomas J.; Smith, Richard D.; Wiley, H. S.; Thrall, Brian D.

    2012-03-29

    To understand how integration of multiple data types can help decipher cellular responses at the systems level, we analyzed the mitogenic response of human mammary epithelial cells to epidermal growth factor (EGF) using whole genome microarrays, mass spectrometry-based proteomics and large-scale western blots with over 1000 antibodies. A time course analysis revealed significant differences in the expression of 3172 genes and 596 proteins, including protein phosphorylation changes measured by western blot. Integration of these disparate data types showed that each contributed qualitatively different components to the observed cell response to EGF and that varying degrees of concordance in gene expression and protein abundance measurements could be linked to specific biological processes. Networks inferred from individual data types were relatively limited, whereas networks derived from the integrated data recapitulated the known major cellular responses to EGF and exhibited more highly connected signaling nodes than networks derived from any individual dataset. While cell cycle regulatory pathways were altered as anticipated, we found the most robust response to mitogenic concentrations of EGF was induction of matrix metalloprotease cascades, highlighting the importance of the EGFR system as a regulator of the extracellular environment. These results demonstrate the value of integrating multiple levels of biological information to more accurately reconstruct networks of cellular response.

  9. Abelian Chern endash Simons theory. II. A functional integral approach

    International Nuclear Information System (INIS)

    Manoliu, M.

    1998-01-01

    Following Witten, [Commun. Math. Phys. 21, 351 endash 399 (1989)] we approach the Abelian quantum Chern endash Simons (CS) gauge theory from a Feynman functional integral point of view. We show that for 3-manifolds with and without a boundary the formal functional integral definitions lead to mathematically proper expressions that agree with the results from the rigorous construction [J. Math. Phys. 39, 170 endash 206 (1998)] of the Abelian CS topological quantum field theory via geometric quantization. copyright 1998 American Institute of Physics

  10. Dynamic integration of residential building design and green energies : the Bireth approach : building integrated renewable energy total harvest approach

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, K.P. [Hong Kong Univ., Hong Kong (China). Dept. of Architecture; Luk, C.L.P. [Chu Hai College of Higher Education, Hong Kong (China). Dept. of Architecture; Wong, S.T. [Hong Kong Univ., Hong Kong (China). Div. of Arts and Humanities, SPACE; Chung, S.L.; Fung, K.S.; Leung, M.F. [Hong Kong Inst. of Vocational Education, Hong Kong (China)

    2006-07-01

    Renewable energy sources that are commonly used in buildings include solar energy, wind energy and rainwater collection. High quality environmentally responsive residential buildings are designed to provide good insulation in winter and solar shading in summer. However, this study demonstrated that the green energy design in residential buildings is not usually well integrated. For example, windows with clear double or triple glazed glass, allow good penetration of sunlight during the day in winter, but are not further dynamically insulated for when the sun goes down to avoid heat loss from the building. Additionally, good solar static shading devices often block much needed daylight on cloudy winter days. These examples emphasize the lack of an integrated approach to gain the best advantage of green energies and to minimize energy costs in residential buildings. This study addressed issues facing the integrated approach with particular reference to the design of a small residential building in rural Beijing. The design included a new approach for interpreting a traditional Beijing court yard house in the modern Beijing rural context, while integrating multi-responding innovative green energy applications derived from first principles. This paper also presented a proposal for a village house in Hong Kong to harvest as much renewable energies as possible, primarily wind energy and solar energy, that come into contact with the building. The purpose was to work towards a renewable energy approach for buildings, namely the Bireth approach, which will benefit practically all houses by making them zero energy houses. The paper described the feasibility of integrating renewable energies in buildings to fulfill performance requirements such improving ventilation, providing warm interiors, drying clothes, or storing solar and wind energies into power batteries. The challenges facing the development of a proposed micro solar hot air turbine were also presented. 15 refs., 6

  11. A design approach for integrating thermoelectric devices using topology optimization

    International Nuclear Information System (INIS)

    Soprani, S.; Haertel, J.H.K.; Lazarov, B.S.; Sigmund, O.; Engelbrecht, K.

    2016-01-01

    Highlights: • The integration of a thermoelectric (TE) cooler into a robotic tool is optimized. • Topology optimization is suggested as design tool for TE integrated systems. • A 3D optimization technique using temperature dependent TE properties is presented. • The sensitivity of the optimization process to the boundary conditions is studied. • A working prototype is constructed and compared to the model results. - Abstract: Efficient operation of thermoelectric devices strongly relies on the thermal integration into the energy conversion system in which they operate. Effective thermal integration reduces the temperature differences between the thermoelectric module and its thermal reservoirs, allowing the system to operate more efficiently. This work proposes and experimentally demonstrates a topology optimization approach as a design tool for efficient integration of thermoelectric modules into systems with specific design constraints. The approach allows thermal layout optimization of thermoelectric systems for different operating conditions and objective functions, such as temperature span, efficiency, and power recovery rate. As a specific application, the integration of a thermoelectric cooler into the electronics section of a downhole oil well intervention tool is investigated, with the objective of minimizing the temperature of the cooled electronics. Several challenges are addressed: ensuring effective heat transfer from the load, minimizing the thermal resistances within the integrated system, maximizing the thermal protection of the cooled zone, and enhancing the conduction of the rejected heat to the oil well. The design method incorporates temperature dependent properties of the thermoelectric device and other materials. The 3D topology optimization model developed in this work was used to design a thermoelectric system, complete with insulation and heat sink, that was produced and tested. Good agreement between experimental results and

  12. An integrated approach towards future ballistic neck protection materials selection.

    Science.gov (United States)

    Breeze, John; Helliker, Mark; Carr, Debra J

    2013-05-01

    Ballistic protection for the neck has historically taken the form of collars attached to the ballistic vest (removable or fixed), but other approaches, including the development of prototypes incorporating ballistic material into the collar of an under body armour shirt, are now being investigated. Current neck collars incorporate the same ballistic protective fabrics as the soft armour of the remaining vest, reflecting how ballistic protective performance alone has historically been perceived as the most important property for neck protection. However, the neck has fundamental differences from the thorax in terms of anatomical vulnerability, flexibility and equipment integration, necessitating a separate solution from the thorax in terms of optimal materials selection. An integrated approach towards the selection of the most appropriate combination of materials to be used for each of the two potential designs of future neck protection has been developed. This approach requires evaluation of the properties of each potential material in addition to ballistic performance alone, including flexibility, mass, wear resistance and thermal burden. The aim of this article is to provide readers with an overview of this integrated approach towards ballistic materials selection and an update of its current progress in the development of future ballistic neck protection.

  13. Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.

    Science.gov (United States)

    Kang, Hahk-Soo

    2017-02-01

    Genomics-based methods are now commonplace in natural products research. A phylogeny-guided mining approach provides a means to quickly screen a large number of microbial genomes or metagenomes in search of new biosynthetic gene clusters of interest. In this approach, biosynthetic genes serve as molecular markers, and phylogenetic trees built with known and unknown marker gene sequences are used to quickly prioritize biosynthetic gene clusters for their metabolites characterization. An increase in the use of this approach has been observed for the last couple of years along with the emergence of low cost sequencing technologies. The aim of this review is to discuss the basic concept of a phylogeny-guided mining approach, and also to provide examples in which this approach was successfully applied to discover new natural products from microbial genomes and metagenomes. I believe that the phylogeny-guided mining approach will continue to play an important role in genomics-based natural products research.

  14. Integration of genomic information into sport horse breeding programs for optimization of accuracy of selection.

    Science.gov (United States)

    Haberland, A M; König von Borstel, U; Simianer, H; König, S

    2012-09-01

    Reliable selection criteria are required for young riding horses to increase genetic gain by increasing accuracy of selection and decreasing generation intervals. In this study, selection strategies incorporating genomic breeding values (GEBVs) were evaluated. Relevant stages of selection in sport horse breeding programs were analyzed by applying selection index theory. Results in terms of accuracies of indices (r(TI) ) and relative selection response indicated that information on single nucleotide polymorphism (SNP) genotypes considerably increases the accuracy of breeding values estimated for young horses without own or progeny performance. In a first scenario, the correlation between the breeding value estimated from the SNP genotype and the true breeding value (= accuracy of GEBV) was fixed to a relatively low value of r(mg) = 0.5. For a low heritability trait (h(2) = 0.15), and an index for a young horse based only on information from both parents, additional genomic information doubles r(TI) from 0.27 to 0.54. Including the conventional information source 'own performance' into the before mentioned index, additional SNP information increases r(TI) by 40%. Thus, particularly with regard to traits of low heritability, genomic information can provide a tool for well-founded selection decisions early in life. In a further approach, different sources of breeding values (e.g. GEBV and estimated breeding values (EBVs) from different countries) were combined into an overall index when altering accuracies of EBVs and correlations between traits. In summary, we showed that genomic selection strategies have the potential to contribute to a substantial reduction in generation intervals in horse breeding programs.

  15. Nuclear agriculture and biotechnology: integrated approaches for crop improvement

    International Nuclear Information System (INIS)

    Suprasanna, P.; Venugopalan, V.

    2017-01-01

    Use of radiation and radioisotopes in agriculture is one of the most important fields of peaceful applications of atomic energy for societal benefit. They are used to induce genetic variability in crop plants to develop improved mutant varieties, to manage insect pests, to monitor fate and persistence of pesticides, to study fertilizer use efficiency and plant micronutrient uptake and also to preserve agricultural produce. So far, BARC has developed and released 42 Trombay mutant varieties in oilseeds (groundnut, mustard, soybean, sunflower), pulses (pigeonpea, blackgram, greengram, cowpea), rice and jute for commercial cultivation across the nation. Mutant characterization has been benefitted by genomics approaches and availability of crop genome sequencing. In this regard, studies are underway to utilize mutant germplasm for molecular characterization and understanding trait modification. The nuclear technologies have benefited the farmers, traders and end-users and will continue to play a significant role in addressing food and nutritional security. In this presentation, an overview will be given on the activities of the NABTD in the field of nuclear agriculture and biotechnology

  16. Path-integral approach to resonant electron-molecule scattering

    International Nuclear Information System (INIS)

    Winterstetter, M.; Domcke, W.

    1993-01-01

    A path-integral formulation of resonant electron-molecule scattering is developed within the framework of the projection-operator formalism of scattering theory. The formation and decay of resonances is treated in real time as a quantum-mechanical electronic-tunneling process, modified by the coupling of the electronic motion with the nuclear degrees of freedom. It is shown that the electronic continuum can be summed over in the path-integral formulation, resulting formally in the path integral for an effective two-state system with coupling to vibrations. The harmonic-oscillator approximation is adopted for the vibrational motion in the present work. Approximation methods are introduced which render the numerical evaluation of the sum over paths feasible for up to ∼10 3 elementary time slices. The theory is numerically realized for simple but nontrivial models representing the 2 Π g d-wave shape resonance in e - +N 2 collisions and the 2 Σ u + p-wave shape resonance in e - +H 2 collisions, respectively. The accuracy of the path-integral results is assessed by comparison with exact numerical reference data for these models. The essential virtue of the path-integral approach is the fact that the computational effort scales at most linearly with the number of vibrational degrees of freedom. The path-integral method is thus well suited to treat electron collisions with polyatomic molecules and molecular aggregates

  17. Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old

    Directory of Open Access Journals (Sweden)

    Ozand Pinar T

    2010-06-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross-species comparative analysis coupled with copy number alterations (CNA of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species. Results We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF-β signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation. Conclusions The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC.

  18. Evaluating the Cassandra NoSQL Database Approach for Genomic Data Persistency

    Directory of Open Access Journals (Sweden)

    Rodrigo Aniceto

    2015-01-01

    Full Text Available Rapid advances in high-throughput sequencing techniques have created interesting computational challenges in bioinformatics. One of them refers to management of massive amounts of data generated by automatic sequencers. We need to deal with the persistency of genomic data, particularly storing and analyzing these large-scale processed data. To find an alternative to the frequently considered relational database model becomes a compelling task. Other data models may be more effective when dealing with a very large amount of nonconventional data, especially for writing and retrieving operations. In this paper, we discuss the Cassandra NoSQL database approach for storing genomic data. We perform an analysis of persistency and I/O operations with real data, using the Cassandra database system. We also compare the results obtained with a classical relational database system and another NoSQL database approach, MongoDB.

  19. Evaluating the Cassandra NoSQL Database Approach for Genomic Data Persistency

    Science.gov (United States)

    Aniceto, Rodrigo; Xavier, Rene; Guimarães, Valeria; Hondo, Fernanda; Holanda, Maristela; Walter, Maria Emilia; Lifschitz, Sérgio

    2015-01-01

    Rapid advances in high-throughput sequencing techniques have created interesting computational challenges in bioinformatics. One of them refers to management of massive amounts of data generated by automatic sequencers. We need to deal with the persistency of genomic data, particularly storing and analyzing these large-scale processed data. To find an alternative to the frequently considered relational database model becomes a compelling task. Other data models may be more effective when dealing with a very large amount of nonconventional data, especially for writing and retrieving operations. In this paper, we discuss the Cassandra NoSQL database approach for storing genomic data. We perform an analysis of persistency and I/O operations with real data, using the Cassandra database system. We also compare the results obtained with a classical relational database system and another NoSQL database approach, MongoDB. PMID:26558254

  20. An optimized electroporation approach for efficient CRISPR/Cas9 genome editing in murine zygotes.

    Directory of Open Access Journals (Sweden)

    Simon E Tröder

    Full Text Available Electroporation of zygotes represents a rapid alternative to the elaborate pronuclear injection procedure for CRISPR/Cas9-mediated genome editing in mice. However, current protocols for electroporation either require the investment in specialized electroporators or corrosive pre-treatment of zygotes which compromises embryo viability. Here, we describe an easily adaptable approach for the introduction of specific mutations in C57BL/6 mice by electroporation of intact zygotes using a common electroporator with synthetic CRISPR/Cas9 components and minimal technical requirement. Direct comparison to conventional pronuclear injection demonstrates significantly reduced physical damage and thus improved embryo development with successful genome editing in up to 100% of living offspring. Hence, our novel approach for Easy Electroporation of Zygotes (EEZy allows highly efficient generation of CRISPR/Cas9 transgenic mice while reducing the numbers of animals required.

  1. Evaluating the Cassandra NoSQL Database Approach for Genomic Data Persistency.

    Science.gov (United States)

    Aniceto, Rodrigo; Xavier, Rene; Guimarães, Valeria; Hondo, Fernanda; Holanda, Maristela; Walter, Maria Emilia; Lifschitz, Sérgio

    2015-01-01

    Rapid advances in high-throughput sequencing techniques have created interesting computational challenges in bioinformatics. One of them refers to management of massive amounts of data generated by automatic sequencers. We need to deal with the persistency of genomic data, particularly storing and analyzing these large-scale processed data. To find an alternative to the frequently considered relational database model becomes a compelling task. Other data models may be more effective when dealing with a very large amount of nonconventional data, especially for writing and retrieving operations. In this paper, we discuss the Cassandra NoSQL database approach for storing genomic data. We perform an analysis of persistency and I/O operations with real data, using the Cassandra database system. We also compare the results obtained with a classical relational database system and another NoSQL database approach, MongoDB.

  2. A pan-genomic approach to understand the basis of host adaptation in Achromobacter.

    Science.gov (United States)

    Jeukens, J; Freschi, L; Vincent, A T; Emond-Rheault, J G; Kukavica-Ibrulj, I; Charette, S J; Levesque, R C

    2017-04-05

    Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis (CF) lung infections. Species of this genus are ubiquitous in the environment, can outcompete resident microbiota, and are resistant to commonly used disinfectants as well as antibiotics. Nevertheless, the Achromobacter genus suffers from difficulties in diagnosis, unresolved taxonomy and limited understanding of how it adapts to the CF lung, not to mention other host environments. The goals of this first genus-wide comparative genomics study were to clarify the taxonomy of this genus and identify genomic features associated with pathogenicity and host adaptation. This was done with a widely applicable approach based on pan-genome analysis. First, using all publicly available genomes, a combination of phylogenetic analysis based on 1,780 conserved genes with average nucleotide identity and accessory genome composition allowed the identification of a largely clinical lineage composed of A. xylosoxidans A insuavis A. dolens and A. ruhlandii. Within this lineage, we identified 35 positively selected genes involved in metabolism, regulation and efflux-mediated antibiotic resistance. Second, resistome analysis showed that this clinical lineage carried additional antibiotic resistance genes compared to other isolates. Finally, we identified putative mobile elements that contribute 53% of the genus's resistome and support horizontal gene transfer between Achromobacter and other ecologically similar genera. This study provides strong phylogenetic and pan-genomic bases to motivate further research on Achromobacter, and contributes to the understanding of opportunistic pathogen evolution. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome.

    Directory of Open Access Journals (Sweden)

    Gary Hon

    2008-10-01

    Full Text Available Computational methods to identify functional genomic elements using genetic information have been very successful in determining gene structure and in identifying a handful of cis-regulatory elements. But the vast majority of regulatory elements have yet to be discovered, and it has become increasingly apparent that their discovery will not come from using genetic information alone. Recently, high-throughput technologies have enabled the creation of information-rich epigenetic maps, most notably for histone modifications. However, tools that search for functional elements using this epigenetic information have been lacking. Here, we describe an unsupervised learning method called ChromaSig to find, in an unbiased fashion, commonly occurring chromatin signatures in both tiling microarray and sequencing data. Applying this algorithm to nine chromatin marks across a 1% sampling of the human genome in HeLa cells, we recover eight clusters of distinct chromatin signatures, five of which correspond to known patterns associated with transcriptional promoters and enhancers. Interestingly, we observe that the distinct chromatin signatures found at enhancers mark distinct functional classes of enhancers in terms of transcription factor and coactivator binding. In addition, we identify three clusters of novel chromatin signatures that contain evolutionarily conserved sequences and potential cis-regulatory elements. Applying ChromaSig to a panel of 21 chromatin marks mapped genomewide by ChIP-Seq reveals 16 classes of genomic elements marked by distinct chromatin signatures. Interestingly, four classes containing enrichment for repressive histone modifications appear to be locally heterochromatic sites and are enriched in quickly evolving regions of the genome. The utility of this approach in uncovering novel, functionally significant genomic elements will aid future efforts of genome annotation via chromatin modifications.

  4. Whole-genome sequencing approaches for conservation biology: Advantages, limitations and practical recommendations.

    Science.gov (United States)

    Fuentes-Pardo, Angela P; Ruzzante, Daniel E

    2017-10-01

    Whole-genome resequencing (WGR) is a powerful method for addressing fundamental evolutionary biology questions that have not been fully resolved using traditional methods. WGR includes four approaches: the sequencing of individuals to a high depth of coverage with either unresolved or resolved haplotypes, the sequencing of population genomes to a high depth by mixing equimolar amounts of unlabelled-individual DNA (Pool-seq) and the sequencing of multiple individuals from a population to a low depth (lcWGR). These techniques require the availability of a reference genome. This, along with the still high cost of shotgun sequencing and the large demand for computing resources and storage, has limited their implementation in nonmodel species with scarce genomic resources and in fields such as conservation biology. Our goal here is to describe the various WGR methods, their pros and cons and potential applications in conservation biology. WGR offers an unprecedented marker density and surveys a wide diversity of genetic variations not limited to single nucleotide polymorphisms (e.g., structural variants and mutations in regulatory elements), increasing their power for the detection of signatures of selection and local adaptation as well as for the identification of the genetic basis of phenotypic traits and diseases. Currently, though, no single WGR approach fulfils all requirements of conservation genetics, and each method has its own limitations and sources of potential bias. We discuss proposed ways to minimize such biases. We envision a not distant future where the analysis of whole genomes becomes a routine task in many nonmodel species and fields including conservation biology. © 2017 John Wiley & Sons Ltd.

  5. Babenko’s Approach to Abel’s Integral Equations

    Directory of Open Access Journals (Sweden)

    Chenkuan Li

    2018-03-01

    Full Text Available The goal of this paper is to investigate the following Abel’s integral equation of the second kind: y ( t + λ Γ ( α ∫ 0 t ( t − τ α − 1 y ( τ d τ = f ( t , ( t > 0 and its variants by fractional calculus. Applying Babenko’s approach and fractional integrals, we provide a general method for solving Abel’s integral equation and others with a demonstration of different types of examples by showing convergence of series. In particular, we extend this equation to a distributional space for any arbitrary α ∈ R by fractional operations of generalized functions for the first time and obtain several new and interesting results that cannot be realized in the classical sense or by the Laplace transform.

  6. Drugs of Abuse and Addiction: An integrated approach to teaching.

    Science.gov (United States)

    Miller, Lindsey N; Mercer, Susan L

    2017-05-01

    To describe the design, implementation, and student perceptions of a Drugs of Abuse and Addiction elective course utilizing an integrated teaching model. Third-year pharmacy students enrolled in the two credit hour elective. Teaching methodology included didactic lecture, journal club, simulated addiction assignment with reflection, debates, external speakers, site visit to a residential drug court program and research paper with presentation. A course objective survey was administered upon course completion. All students strongly agreed that having science- and clinical-based faculty members develop and deliver course content was beneficial. Additionally, all students agree to strongly agree that their research project helped them integrate and comprehend the science and practice surrounding drugs of abuse and addiction. Students enjoyed an integrated teaching approach and multiple teaching methodologies leading to increased engagement and enhancement of student learning. Course enrollment was beneficial for personalized learning, but limited student perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Integrated Approach to the Accident Evaluation for Advanced LWRs

    International Nuclear Information System (INIS)

    Oriolo, F.; Paci, S.

    1998-01-01

    The present paper discusses some relevant phenomena occurring in advanced LWRs during postulated accident scenarios. In particular, the operation of ESF is the starting point for analysis of those phenomena that cause the mutual influence between PS and containment in these plants. As a consequence, it is highlighted as accident analyses which treat PS and containment phenomena completely separated may be not adequate when applied to innovate reactors. Exemplified thermal-hydraulic analysis are presented for AP600 and SBWR, using the FUMO integrated model, for highlight accident evolution taking into account these interactions. The architecture of this integrated code is presented highlighting the importance of an integrated approach to the safety analysis in innovative reactors. (author)

  8. Systems Approaches: A Global and Historical Perspective on Integrative Medicine

    Science.gov (United States)

    2012-01-01

    The globalization of healing systems is a dance of cultural awareness and cultural dominance that has arisen throughout history. With the development of greater communication and interest in whole-systems approaches to healing, the opportunity for the development of a global perspective on healing has emerged with new life force. The birth of integrative holistic healing systems in the West, such as naturopathic, homeopathic, anthroposophic, integral and functional medicine, and others, echoes the ocean of wisdom present in traditional healing systems, such as traditional Chinese medicine (TCM) and Ayurveda. In working to integrate the lessons from these systems, we see the inextricable link between man and the natural world, we work to understand the root cause of disease, we focus on the whole person to return balance, and we use empiric observation in large populations over time to grasp the interrelationships inherent in the whole-systems view of illness and wellness. PMID:24278794

  9. Integrated Transport Planning Framework Involving Combined Utility Regret Approach

    DEFF Research Database (Denmark)

    Wang, Yang; Monzon, Andres; Di Ciommo, Floridea

    2014-01-01

    Sustainable transport planning requires an integrated approach involving strategic planning, impact analysis, and multicriteria evaluation. This study aimed at relaxing the utility-based decision-making assumption by newly embedding anticipated-regret and combined utility regret decision mechanisms...... in a framework for integrated transport planning. The framework consisted of a two-round Delphi survey, integrated land use and transport model for Madrid, and multicriteria analysis. Results show that (a) the regret-based ranking has a similar mean but larger variance than the utility-based ranking does, (b......) the least-regret scenario forms a compromise between the desired and the expected scenarios, (c) the least-regret scenario can lead to higher user benefits in the short term and lower user benefits in the long term, (d) the utility-based, the regret-based, and the combined utility- and regret...

  10. RISK MANAGEMENT: AN INTEGRATED APPROACH TO RISK MANAGEMENT AND ASSESSMENT

    OpenAIRE

    Szabo Alina

    2012-01-01

    Purpose: The objective of this paper is to offer an overview over risk management cycle by focusing on prioritization and treatment, in order to ensure an integrated approach to risk management and assessment, and establish the ‘top 8-12’ risks report within the organization. The interface with Internal Audit is ensured by the implementation of the scoring method to prioritize risks collected from previous generated risk report. Methodology/approach: Using evidence from other research in ...

  11. Flexible Web services integration: a novel personalised social approach

    Science.gov (United States)

    Metrouh, Abdelmalek; Mokhati, Farid

    2018-05-01

    Dynamic composition or integration remains one of the key objectives of Web services technology. This paper aims to propose an innovative approach of dynamic Web services composition based on functional and non-functional attributes and individual preferences. In this approach, social networks of Web services are used to maintain interactions between Web services in order to select and compose Web services that are more tightly related to user's preferences. We use the concept of Web services community in a social network of Web services to reduce considerably their search space. These communities are created by the direct involvement of Web services providers.

  12. A manufacturable process integration approach for graphene devices

    Science.gov (United States)

    Vaziri, Sam; Lupina, Grzegorz; Paussa, Alan; Smith, Anderson D.; Henkel, Christoph; Lippert, Gunther; Dabrowski, Jarek; Mehr, Wolfgang; Östling, Mikael; Lemme, Max C.

    2013-06-01

    In this work, we propose an integration approach for double gate graphene field effect transistors. The approach includes a number of process steps that are key for future integration of graphene in microelectronics: bottom gates with ultra-thin (2 nm) high-quality thermally grown SiO2 dielectrics, shallow trench isolation between devices and atomic layer deposited Al2O3 top gate dielectrics. The complete process flow is demonstrated with fully functional GFET transistors and can be extended to wafer scale processing. We assess, through simulation, the effects of the quantum capacitance and band bending in the silicon substrate on the effective electric fields in the top and bottom gate oxide. The proposed process technology is suitable for other graphene-based devices such as graphene-based hot electron transistors and photodetectors.

  13. A LDA-based approach to promoting ranking diversity for genomics information retrieval.

    Science.gov (United States)

    Chen, Yan; Yin, Xiaoshi; Li, Zhoujun; Hu, Xiaohua; Huang, Jimmy Xiangji

    2012-06-11

    In the biomedical domain, there are immense data and tremendous increase of genomics and biomedical relevant publications. The wealth of information has led to an increasing amount of interest in and need for applying information retrieval techniques to access the scientific literature in genomics and related biomedical disciplines. In many cases, the desired information of a query asked by biologists is a list of a certain type of entities covering different aspects that are related to the question, such as cells, genes, diseases, proteins, mutations, etc. Hence, it is important of a biomedical IR system to be able to provide relevant and diverse answers to fulfill biologists' information needs. However traditional IR model only concerns with the relevance between retrieved documents and user query, but does not take redundancy between retrieved documents into account. This will lead to high redundancy and low diversity in the retrieval ranked lists. In this paper, we propose an approach which employs a topic generative model called Latent Dirichlet Allocation (LDA) to promoting ranking diversity for biomedical information retrieval. Different from other approaches or models which consider aspects on word level, our approach assumes that aspects should be identified by the topics of retrieved documents. We present LDA model to discover topic distribution of retrieval passages and word distribution of each topic dimension, and then re-rank retrieval results with topic distribution similarity between passages based on N-size slide window. We perform our approach on TREC 2007 Genomics collection and two distinctive IR baseline runs, which can achieve 8% improvement over the highest Aspect MAP reported in TREC 2007 Genomics track. The proposed method is the first study of adopting topic model to genomics information retrieval, and demonstrates its effectiveness in promoting ranking diversity as well as in improving relevance of ranked lists of genomics search

  14. Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

    Science.gov (United States)

    Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

    2017-01-01

    Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x

  15. The integrated approach to teaching programming in secondary school

    Directory of Open Access Journals (Sweden)

    Martynyuk A.A.

    2018-02-01

    Full Text Available the article considers an integrated approach to teaching programming with the use of technologies of computer modeling and 3D-graphics, allowing to improve the quality of education. It is shown that this method will allow you to systematize knowledge, improve the level of motivation through the inclusion of relevant technologies, to develop skills of project activities, to strengthen interdisciplinary connections, and promotes professional and personal self-determination of students of secondary school.

  16. Workplace mental health: developing an integrated intervention approach

    Science.gov (United States)

    2014-01-01

    Background Mental health problems are prevalent and costly in working populations. Workplace interventions to address common mental health problems have evolved relatively independently along three main threads or disciplinary traditions: medicine, public health, and psychology. In this Debate piece, we argue that these three threads need to be integrated to optimise the prevention of mental health problems in working populations. Discussion To realise the greatest population mental health benefits, workplace mental health intervention needs to comprehensively 1) protect mental health by reducing work–related risk factors for mental health problems; 2) promote mental health by developing the positive aspects of work as well as worker strengths and positive capacities; and 3) address mental health problems among working people regardless of cause. We outline the evidence supporting such an integrated intervention approach and consider the research agenda and policy developments needed to move towards this goal, and propose the notion of integrated workplace mental health literacy. Summary An integrated approach to workplace mental health combines the strengths of medicine, public health, and psychology, and has the potential to optimise both the prevention and management of mental health problems in the workplace. PMID:24884425

  17. Genomic integration and germline transmission of plasmid injected into crustacean Daphnia magna eggs.

    Directory of Open Access Journals (Sweden)

    Yasuhiko Kato

    Full Text Available The water flea, Daphnia, has been the subject of study in ecology, evolution, and environmental sciences for decades. Over the last few years, expressed sequence tags and a genome sequence have been determined. In addition, functional approaches of overexpression and gene silencing based on microinjection of RNAs into eggs have been established. However, the transient nature of these approaches prevents us from analyzing gene functions in later stages of development. To overcome this limitation, transgenesis would become a key tool. Here we report establishment of a transgenic line using microinjection of plasmid into Daphnia magna eggs. The green fluorescent protein (GFP gene fused with the D. magna histone H2B gene under the control of a promoter/enhancer region of the elongation factor 1α-1 (EF1α-1 gene, EF1α-1::H2B-GFP, was used as a reporter providing high resolution visualization of active chromatin. Transgenic lines were obtained from 0.67% of the total fertile adults that survived the injections. One of the transgenic animals, which exhibited fluorescence in the nuclei of cells during embryogenesis and oogenesis, had two copies of EF1α-1::H2B-GFP in a head-to-tail array. This is the first report of a transgenesis technique in Daphnia and, together with emerging genome sequences, will be useful for advancing knowledge of the molecular biology of Daphnia.

  18. An Integrated Metabolomic and Genomic Mining Workflow to Uncover the Biosynthetic Potential of Bacteria

    DEFF Research Database (Denmark)

    Månsson, Maria; Vynne, Nikolaj Grønnegaard; Klitgaard, Andreas

    2016-01-01

    Microorganisms are a rich source of bioactives; however, chemical identification is a major bottleneck. Strategies that can prioritize the most prolific microbial strains and novel compounds are of great interest. Here, we present an integrated approach to evaluate the biosynthetic richness in ba...

  19. GenomeCAT: a versatile tool for the analysis and integrative visualization of DNA copy number variants.

    Science.gov (United States)

    Tebel, Katrin; Boldt, Vivien; Steininger, Anne; Port, Matthias; Ebert, Grit; Ullmann, Reinhard

    2017-01-06

    The analysis of DNA copy number variants (CNV) has increasing impact in the field of genetic diagnostics and research. However, the interpretation of CNV data derived from high resolution array CGH or NGS platforms is complicated by the considerable variability of the human genome. Therefore, tools for multidimensional data analysis and comparison of patient cohorts are needed to assist in the discrimination of clinically relevant CNVs from others. We developed GenomeCAT, a standalone Java application for the analysis and integrative visualization of CNVs. GenomeCAT is composed of three modules dedicated to the inspection of single cases, comparative analysis of multidimensional data and group comparisons aiming at the identification of recurrent aberrations in patients sharing the same phenotype, respectively. Its flexible import options ease the comparative analysis of own results derived from microarray or NGS platforms with data from literature or public depositories. Multidimensional data obtained from different experiment types can be merged into a common data matrix to enable common visualization and analysis. All results are stored in the integrated MySQL database, but can also be exported as tab delimited files for further statistical calculations in external programs. GenomeCAT offers a broad spectrum of visualization and analysis tools that assist in the evaluation of CNVs in the context of other experiment data and annotations. The use of GenomeCAT does not require any specialized computer skills. The various R packages implemented for data analysis are fully integrated into GenomeCATs graphical user interface and the installation process is supported by a wizard. The flexibility in terms of data import and export in combination with the ability to create a common data matrix makes the program also well suited as an interface between genomic data from heterogeneous sources and external software tools. Due to the modular architecture the functionality of

  20. [Integrative approach in the psychotherapy of borderline personality disorder].

    Science.gov (United States)

    Kuritárné Szabó, Ildikó

    2012-01-01

    In the last 20 years six psychotherapy methods have been developed specifically for borderline personality disorder. Solid RCT evidences suggests the efficacy of all the methods. Roughly equivalent improvement was obtained from the different types of psychotherapies. Today we have reached a new phase of the borderline "psychotherapy boom", the integrative approach. According to the integrative treatment advocates we should not choose among these effective treatments but we can incorporate in the therapy all the components that work. The integrative approach uses general factors common to all effective therapies, combined with specific treatment techniques taken from different therapies in order to treat the given patient's psychopathology. These common factors are: coherent framework; attention to strategies for building strong positive alliance and maintaining patient motivation; creating a safe and structured therapeutic environment; clear treatment frame; transparency of the goals and roles; focus upon presenting problems; higher level therapeutic activity; here-and-now focus; and facilitating self-reflection. Treatment focuses on change while maintaining a validating and supportive stance. General strategies can be supplemented by more specific techniques such as cognitive-behavioral interventions for reducing maladaptive behavior, training for developing emotion regulation skills and interpersonal skills coming from dialectical behavior therapy. Methods drawn from psychodynamic approaches can be used for the modification of underlying interpersonal cognitive-emotional schemas.

  1. MicroScope—an integrated microbial resource for the curation and comparative analysis of genomic and metabolic data

    Science.gov (United States)

    Vallenet, David; Belda, Eugeni; Calteau, Alexandra; Cruveiller, Stéphane; Engelen, Stefan; Lajus, Aurélie; Le Fèvre, François; Longin, Cyrille; Mornico, Damien; Roche, David; Rouy, Zoé; Salvignol, Gregory; Scarpelli, Claude; Thil Smith, Adam Alexander; Weiman, Marion; Médigue, Claudine

    2013-01-01

    MicroScope is an integrated platform dedicated to both the methodical updating of microbial genome annotation and to comparative analysis. The resource provides data from completed and ongoing genome projects (automatic and expert annotations), together with data sources from post-genomic experiments (i.e. transcriptomics, mutant collections) allowing users to perfect and improve the understanding of gene functions. MicroScope (http://www.genoscope.cns.fr/agc/microscope) combines tools and graphical interfaces to analyse genomes and to perform the manual curation of gene annotations in a comparative context. Since its first publication in January 2006, the system (previously named MaGe for Magnifying Genomes) has been continuously extended both in terms of data content and analysis tools. The last update of MicroScope was published in 2009 in the Database journal. Today, the resource contains data for >1600 microbial genomes, of which ∼300 are manually curated and maintained by biologists (1200 personal accounts today). Expert annotations are continuously gathered in the MicroScope database (∼50 000 a year), contributing to the improvement of the quality of microbial genomes annotations. Improved data browsing and searching tools have been added, original tools useful in the context of expert annotation have been developed and integrated and the website has been significantly redesigned to be more user-friendly. Furthermore, in the context of the European project Microme (Framework Program 7 Collaborative Project), MicroScope is becoming a resource providing for the curation and analysis of both genomic and metabolic data. An increasing number of projects are related to the study of environmental bacterial (meta)genomes that are able to metabolize a large variety of chemical compounds that may be of high industrial interest. PMID:23193269

  2. Integration of distributed system simulation tools for a holistic approach to integrated building and system design

    NARCIS (Netherlands)

    Radosevic, M.; Hensen, J.L.M.; Wijsman, A.J.T.M.; Hensen, J.L.M.; Lain, M.

    2004-01-01

    Advanced architectural developments require an integrated approach to design where simulation tools available today deal. only with a small subset of the overall problem. The aim of this study is to enable run time exchange of necessary data at suitable frequency between different simulation

  3. An integrated approach for integrated intelligent instrumentation and control system (I3CS)

    International Nuclear Information System (INIS)

    Jung, C.H.; Kim, J.T.; Kwon, K.C.

    1997-01-01

    Nuclear power plants to guarantee the safety of public should be designed to reduce the operator intervention resulting in operating human errors, identify the process states in transients, and aid to make a decision of their tasks and guide operator actions. For the sake of this purpose, MMIS(MAN-Machine Interface System) in NPPs should be the integrated top-down approach tightly focused on the function-based task analysis including an advanced digital technology, an operator support function, and so on. The advanced I and C research team in KAERI has embarked on developing an Integrated Intelligent Instrumentation and Control System (I 3 CS) for Korea's next generation nuclear power plants. I 3 CS bases the integrated top-down approach on the function-based task analysis, modern digital technology, standardization and simplification, availability and reliability, and protection of investment. (author). 4 refs, 6 figs

  4. An integrated approach for integrated intelligent instrumentation and control system (I{sup 3}CS)

    Energy Technology Data Exchange (ETDEWEB)

    Jung, C H; Kim, J T; Kwon, K C [Korea Atomic Energy Research Inst., Yusong, Taejon (Korea, Republic of)

    1997-07-01

    Nuclear power plants to guarantee the safety of public should be designed to reduce the operator intervention resulting in operating human errors, identify the process states in transients, and aid to make a decision of their tasks and guide operator actions. For the sake of this purpose, MMIS(MAN-Machine Interface System) in NPPs should be the integrated top-down approach tightly focused on the function-based task analysis including an advanced digital technology, an operator support function, and so on. The advanced I and C research team in KAERI has embarked on developing an Integrated Intelligent Instrumentation and Control System (I{sup 3}CS) for Korea`s next generation nuclear power plants. I{sup 3}CS bases the integrated top-down approach on the function-based task analysis, modern digital technology, standardization and simplification, availability and reliability, and protection of investment. (author). 4 refs, 6 figs.

  5. Single-molecule approach to bacterial genomic comparisons via optical mapping.

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Shiguo [Univ. Wisc.-Madison; Kile, A. [Univ. Wisc.-Madison; Bechner, M. [Univ. Wisc.-Madison; Kvikstad, E. [Univ. Wisc.-Madison; Deng, W. [Univ. Wisc.-Madison; Wei, J. [Univ. Wisc.-Madison; Severin, J. [Univ. Wisc.-Madison; Runnheim, R. [Univ. Wisc.-Madison; Churas, C. [Univ. Wisc.-Madison; Forrest, D. [Univ. Wisc.-Madison; Dimalanta, E. [Univ. Wisc.-Madison; Lamers, C. [Univ. Wisc.-Madison; Burland, V. [Univ. Wisc.-Madison; Blattner, F. R. [Univ. Wisc.-Madison; Schwartz, David C. [Univ. Wisc.-Madison

    2004-01-01

    Modern comparative genomics has been established, in part, by the sequencing and annotation of a broad range of microbial species. To gain further insights, new sequencing efforts are now dealing with the variety of strains or isolates that gives a species definition and range; however, this number vastly outstrips our ability to sequence them. Given the availability of a large number of microbial species, new whole genome approaches must be developed to fully leverage this information at the level of strain diversity that maximize discovery. Here, we describe how optical mapping, a single-molecule system, was used to identify and annotate chromosomal alterations between bacterial strains represented by several species. Since whole-genome optical maps are ordered restriction maps, sequenced strains of Shigella flexneri serotype 2a (2457T and 301), Yersinia pestis (CO 92 and KIM), and Escherichia coli were aligned as maps to identify regions of homology and to further characterize them as possible insertions, deletions, inversions, or translocations. Importantly, an unsequenced Shigella flexneri strain (serotype Y strain AMC[328Y]) was optically mapped and aligned with two sequenced ones to reveal one novel locus implicated in serotype conversion and several other loci containing insertion sequence elements or phage-related gene insertions. Our results suggest that genomic rearrangements and chromosomal breakpoints are readily identified and annotated against a prototypic sequenced strain by using the tools of optical mapping.

  6. Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.

    Science.gov (United States)

    Harris, Dennis R; Tanaka, Masashi; Saveliev, Sergei V; Jolivet, Edmond; Earl, Ashlee M; Cox, Michael M; Battista, John R

    2004-10-01

    The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3' ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein.

  7. Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.

    Directory of Open Access Journals (Sweden)

    Dennis R Harris

    2004-10-01

    Full Text Available The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3' ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein.

  8. Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli.

    Science.gov (United States)

    Mangan, Hazel; Gailín, Michael Ó; McStay, Brian

    2017-12-01

    Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid-liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells. © 2017 Federation of European Biochemical Societies.

  9. 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