WorldWideScience

Sample records for genomics portals integrative

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

    OpenAIRE

    Arkin, Adam P.

    2014-01-01

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

  2. MicrobesOnline: an integrated portal for comparative functional genomics

    OpenAIRE

    Joachimiak, Marcin P.

    2014-01-01

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

  3. 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.

  4. 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.

  5. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  6. The genome portal of the Department of Energy Joint Genome Institute: 2014 updates

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, Henrik [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Cantor, Michael [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Dusheyko, Serge [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Hua, Susan [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Poliakov, Alexander [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Shabalov, Igor [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Smirnova, Tatyana [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Grigoriev, Igor V. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Dubchak, Inna [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)

    2013-11-12

    The U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a national user facility, serves the diverse scientific community by providing integrated high-throughput sequencing and computational analysis to enable system-based scientific approaches in support of DOE missions related to clean energy generation and environmental characterization. The JGI Genome Portal (http://genome.jgi.doe.gov) provides unified access to all JGI genomic databases and analytical tools. The JGI maintains extensive data management systems and specialized analytical capabilities to manage and interpret complex genomic data. A user can search, download and explore multiple data sets available for all DOE JGI sequencing projects including their status, assemblies and annotations of sequenced genomes. In this paper, we describe major updates of the Genome Portal in the past 2 years with a specific emphasis on efficient handling of the rapidly growing amount of diverse genomic data accumulated in JGI.

  7. GREAT: a web portal for Genome Regulatory Architecture Tools.

    Science.gov (United States)

    Bouyioukos, Costas; Bucchini, François; Elati, Mohamed; Képès, François

    2016-07-08

    GREAT (Genome REgulatory Architecture Tools) is a novel web portal for tools designed to generate user-friendly and biologically useful analysis of genome architecture and regulation. The online tools of GREAT are freely accessible and compatible with essentially any operating system which runs a modern browser. GREAT is based on the analysis of genome layout -defined as the respective positioning of co-functional genes- and its relation with chromosome architecture and gene expression. GREAT tools allow users to systematically detect regular patterns along co-functional genomic features in an automatic way consisting of three individual steps and respective interactive visualizations. In addition to the complete analysis of regularities, GREAT tools enable the use of periodicity and position information for improving the prediction of transcription factor binding sites using a multi-view machine learning approach. The outcome of this integrative approach features a multivariate analysis of the interplay between the location of a gene and its regulatory sequence. GREAT results are plotted in web interactive graphs and are available for download either as individual plots, self-contained interactive pages or as machine readable tables for downstream analysis. The GREAT portal can be reached at the following URL https://absynth.issb.genopole.fr/GREAT and each individual GREAT tool is available for downloading.

  8. Streptococcus pyogenes polymyxin B-resistant mutants display enhanced ExPortal integrity.

    Science.gov (United States)

    Port, Gary C; Vega, Luis A; Nylander, Andrew B; Caparon, Michael G

    2014-07-01

    The ExPortal protein secretion organelle in Streptococcus pyogenes is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in pstS, encoding a component of a high-affinity Pi transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides.

  9. canEvolve: a web portal for integrative oncogenomics.

    Directory of Open Access Journals (Sweden)

    Mehmet Kemal Samur

    Full Text Available BACKGROUND & OBJECTIVE: Genome-wide profiles of tumors obtained using functional genomics platforms are being deposited to the public repositories at an astronomical scale, as a result of focused efforts by individual laboratories and large projects such as the Cancer Genome Atlas (TCGA and the International Cancer Genome Consortium. Consequently, there is an urgent need for reliable tools that integrate and interpret these data in light of current knowledge and disseminate results to biomedical researchers in a user-friendly manner. We have built the canEvolve web portal to meet this need. RESULTS: canEvolve query functionalities are designed to fulfill most frequent analysis needs of cancer researchers with a view to generate novel hypotheses. canEvolve stores gene, microRNA (miRNA and protein expression profiles, copy number alterations for multiple cancer types, and protein-protein interaction information. canEvolve allows querying of results of primary analysis, integrative analysis and network analysis of oncogenomics data. The querying for primary analysis includes differential gene and miRNA expression as well as changes in gene copy number measured with SNP microarrays. canEvolve provides results of integrative analysis of gene expression profiles with copy number alterations and with miRNA profiles as well as generalized integrative analysis using gene set enrichment analysis. The network analysis capability includes storage and visualization of gene co-expression, inferred gene regulatory networks and protein-protein interaction information. Finally, canEvolve provides correlations between gene expression and clinical outcomes in terms of univariate survival analysis. CONCLUSION: At present canEvolve provides different types of information extracted from 90 cancer genomics studies comprising of more than 10,000 patients. The presence of multiple data types, novel integrative analysis for identifying regulators of oncogenesis, network

  10. Portal dosimetry for VMAT using integrated images obtained during treatment.

    Science.gov (United States)

    Bedford, James L; Hanson, Ian M; Hansen, Vibeke Nordmark

    2014-02-01

    Portal dosimetry provides an accurate and convenient means of verifying dose delivered to the patient. A simple method for carrying out portal dosimetry for volumetric modulated arc therapy (VMAT) is described, together with phantom measurements demonstrating the validity of the approach. Portal images were predicted by projecting dose in the isocentric plane through to the portal image plane, with exponential attenuation and convolution with a double-Gaussian scatter function. Appropriate parameters for the projection were selected by fitting the calculation model to portal images measured on an iViewGT portal imager (Elekta AB, Stockholm, Sweden) for a variety of phantom thicknesses and field sizes. This model was then used to predict the portal image resulting from each control point of a VMAT arc. Finally, all these control point images were summed to predict the overall integrated portal image for the whole arc. The calculated and measured integrated portal images were compared for three lung and three esophagus plans delivered to a thorax phantom, and three prostate plans delivered to a homogeneous phantom, using a gamma index for 3% and 3 mm. A 0.6 cm(3) ionization chamber was used to verify the planned isocentric dose. The sensitivity of this method to errors in monitor units, field shaping, gantry angle, and phantom position was also evaluated by means of computer simulations. The calculation model for portal dose prediction was able to accurately compute the portal images due to simple square fields delivered to solid water phantoms. The integrated images of VMAT treatments delivered to phantoms were also correctly predicted by the method. The proportion of the images with a gamma index of less than unity was 93.7% ± 3.0% (1SD) and the difference between isocenter dose calculated by the planning system and measured by the ionization chamber was 0.8% ± 1.0%. The method was highly sensitive to errors in monitor units and field shape, but less sensitive to

  11. Integrating Space Communication Network Capabilities via Web Portal Technologies

    Science.gov (United States)

    Johnston, Mark D.; Lee, Carlyn-Ann; Lau, Chi-Wung; Cheung, Kar-Ming; Levesque, Michael; Carruth, Butch; Coffman, Adam; Wallace, Mike

    2014-01-01

    We have developed a service portal prototype as part of an investigation into the feasibility of using Java portlet technology as a means of providing integrated access to NASA communications network services. Portal servers provide an attractive platform for this role due to the various built-in collaboration applications they can provide, combined with the possibility to develop custom inter-operating portlets to extent their functionality while preserving common presentation and behavior. This paper describes various options for integration of network services related to planning and scheduling, and results based on use of a popular open-source portal framework. Plans are underway to develop an operational SCaN Service Portal, building on the experiences reported here.

  12. THE ROLE OF ENTERPRISE PORTALS IN ENTERPRISE INTEGRATION

    Directory of Open Access Journals (Sweden)

    Gianina RIZESCU

    2006-01-01

    Full Text Available Today’s enterprises are moving business systems to the Internet - to connect people, business processes, and people to business processes in enterprise and across enterprise boundaries. The portal brings it all together: business processes, departmental sites, knowledge management resources, enterprise management systems, CRM systems, analytics, email, calendars, external content, transactions,administration, workflow, and more. The goal of this paper is to present the role of the Enterprise Portal in internal and external enterprise integration.

  13. Multiple Whole Genome Alignments and Novel Biomedical Applicationsat the VISTA Portal

    Energy Technology Data Exchange (ETDEWEB)

    Brudno, Michael; Poliakov, Alexander; Minovitsky, Simon; Ratnere,Igor; Dubchak, Inna

    2007-02-01

    The VISTA portal for comparative genomics is designed togive biomedical scientists a unified set of tools to lead them from theraw DNA sequences through the alignment and annotation to thevisualization of the results. The VISTA portal also hosts alignments of anumber of genomes computed by our group, allowing users to study regionsof their interest without having to manually download the individualsequences. Here we describe various algorithmic and functionalimprovements implemented in the VISTA portal over the last two years. TheVISTA Portal is accessible at http://genome.lbl.gov/vista.

  14. The Global Genome Biodiversity Network (GGBN) Data Portal.

    Science.gov (United States)

    Droege, Gabriele; Barker, Katharine; Astrin, Jonas J; Bartels, Paul; Butler, Carol; Cantrill, David; Coddington, Jonathan; Forest, Félix; Gemeinholzer, Birgit; Hobern, Donald; Mackenzie-Dodds, Jacqueline; Ó Tuama, Éamonn; Petersen, Gitte; Sanjur, Oris; Schindel, David; Seberg, Ole

    2014-01-01

    The Global Genome Biodiversity Network (GGBN) was formed in 2011 with the principal aim of making high-quality well-documented and vouchered collections that store DNA or tissue samples of biodiversity, discoverable for research through a networked community of biodiversity repositories. This is achieved through the GGBN Data Portal (http://data.ggbn.org), which links globally distributed databases and bridges the gap between biodiversity repositories, sequence databases and research results. Advances in DNA extraction techniques combined with next-generation sequencing technologies provide new tools for genome sequencing. Many ambitious genome sequencing projects with the potential to revolutionize biodiversity research consider access to adequate samples to be a major bottleneck in their workflow. This is linked not only to accelerating biodiversity loss and demands to improve conservation efforts but also to a lack of standardized methods for providing access to genomic samples. Biodiversity biobank-holding institutions urgently need to set a standard of collaboration towards excellence in collections stewardship, information access and sharing and responsible and ethical use of such collections. GGBN meets these needs by enabling and supporting accessibility and the efficient coordinated expansion of biodiversity biobanks worldwide.

  15. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

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

  16. IMP 2.0: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks.

    Science.gov (United States)

    Wong, Aaron K; Krishnan, Arjun; Yao, Victoria; Tadych, Alicja; Troyanskaya, Olga G

    2015-07-01

    IMP (Integrative Multi-species Prediction), originally released in 2012, is an interactive web server that enables molecular biologists to interpret experimental results and to generate hypotheses in the context of a large cross-organism compendium of functional predictions and networks. The system provides biologists with a framework to analyze their candidate gene sets in the context of functional networks, expanding or refining their sets using functional relationships predicted from integrated high-throughput data. IMP 2.0 integrates updated prior knowledge and data collections from the last three years in the seven supported organisms (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Caenorhabditis elegans, and Saccharomyces cerevisiae) and extends function prediction coverage to include human disease. IMP identifies homologs with conserved functional roles for disease knowledge transfer, allowing biologists to analyze disease contexts and predictions across all organisms. Additionally, IMP 2.0 implements a new flexible platform for experts to generate custom hypotheses about biological processes or diseases, making sophisticated data-driven methods easily accessible to researchers. IMP does not require any registration or installation and is freely available for use at http://imp.princeton.edu.

  17. The Genome Portal of the Department of Energy Joint Genome Institute

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, Henrik; Cantor, Michael; Dushekyo, Serge; Hua, Susan; Poliakov, Alexander; Smirnova, Tatyana; Dubchak, Inna

    2014-03-14

    The JGI Genome Portal (http://genome.jgi.doe.gov) provides unified access to all JGI genomic databases and analytical tools. A user can search, download and explore multiple data sets available for all DOE JGI sequencing projects including their status, assemblies and annotations of sequenced genomes. Genome Portal in the past 2 years was significantly updated, with a specific emphasis on efficient handling of the rapidly growing amount of diverse genomic data accumulated in JGI. A critical aspect of handling big data in genomics is the development of visualization and analysis tools that allow scientists to derive meaning from what are otherwise terrabases of inert sequence. An interactive visualization tool developed in the group allows us to explore contigs resulting from a single metagenome assembly. Implemented with modern web technologies that take advantage of the power of the computer's graphical processing unit (gpu), the tool allows the user to easily navigate over a 100,000 data points in multiple dimensions, among many biologically meaningful parameters of a dataset such as relative abundance, contig length, and G+C content.

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

    Science.gov (United States)

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

    2005-01-01

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

  19. Three-dimensional Structure of a Viral Genome-delivery Portal Vertex

    Energy Technology Data Exchange (ETDEWEB)

    A Olia; P Prevelige Jr.; J Johnson; G Cingolani

    2011-12-31

    DNA viruses such as bacteriophages and herpesviruses deliver their genome into and out of the capsid through large proteinaceous assemblies, known as portal proteins. Here, we report two snapshots of the dodecameric portal protein of bacteriophage P22. The 3.25-{angstrom}-resolution structure of the portal-protein core bound to 12 copies of gene product 4 (gp4) reveals a {approx}1.1-MDa assembly formed by 24 proteins. Unexpectedly, a lower-resolution structure of the full-length portal protein unveils the unique topology of the C-terminal domain, which forms a {approx}200-{angstrom}-long {alpha}-helical barrel. This domain inserts deeply into the virion and is highly conserved in the Podoviridae family. We propose that the barrel domain facilitates genome spooling onto the interior surface of the capsid during genome packaging and, in analogy to a rifle barrel, increases the accuracy of genome ejection into the host cell.

  20. A Service Portal for the Integrated SCaN Network

    Science.gov (United States)

    Marx, Sarah R.

    2012-01-01

    The Space Communication and Navigation (SCaN) program office owns the assets and services provided by the Deep Space Network (DSN), Near Earth Network (NEN), and Space Network (SN). At present, these individual networks are operated by different NASA centers--JPL for DSN--and Goddard Space Flight Center (GSFC) for NEN and SN--with separate commitments offices for each center. In the near future, SCaN's program office would like to deploy an integrated service portal which would merge the two commitments offices with the goal of easing the task of user planning for space missions requiring services of two or more of these networks. Following interviews with subject matter experts in this field, use cases were created to include the services and functionality mission users would like to see in this new integrated service portal. These use cases provide a guideline for a mock-up of the design of the user interface for the portal. The benefit of this work will ease the time required and streamline/standardize the process for planning and scheduling SCAN's services for future space missions.

  1. Integrating Thematic Web Portal Capabilities into the NASA Earthdata Web Infrastructure

    Science.gov (United States)

    Wong, Minnie; Baynes, Kathleen E.; Huang, Thomas; McLaughlin, Brett

    2015-01-01

    This poster will present the process of integrating thematic web portal capabilities into the NASA Earth data web infrastructure, with examples from the Sea Level Change Portal. The Sea Level Change Portal will be a source of current NASA research, data and information regarding sea level change. The portal will provide sea level change information through articles, graphics, videos and animations, an interactive tool to view and access sea level change data and a dashboard showing sea level change indicators.

  2. Statistical Methods in Integrative Genomics

    OpenAIRE

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

    2016-01-01

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

  3. Enabling Integration and Synthesis through the Ridge 2000 Data Portal

    Science.gov (United States)

    Ryan, W. B.; Ferrini, V.; Carbotte, S. M.; O'Hara, S.; Arko, R. A.; Bonczkowski, J.; Chan, S.

    2009-12-01

    Achieving an integrated, holistic understanding of global mid-ocean ridge (MOR) processes through the Ridge 2000 Program relies heavily on the sharing of data across disciplinary boundaries. Although most Ridge 2000 research has been focused on three Integrated Study Sites (ISSs), data from throughout the global mid-ocean ridge (MOR) system will also be important in the integration and synthesis phase of the program. The Ridge 2000 Data Portal (www.marine-geo.org/portals/ridge2000) is a resource established to facilitate the sharing, discovery, and integration of Ridge 2000-relevant data by providing data documentation and access. The Data Portal includes an inventory of field programs and activities, raw and derived data files, and access to publications and remote data sets in specialized data systems (e.g. PetDB, www.petdb.org; GenBank, www.ncbi.nlm.nih.gov; NGDC, www.ngdc.noaa.gov). Access to the R2K database is provided through several pathways, including a web-based search interface (www.marine-geo.org/tools/search) that now includes basic and advanced search functionality. New versions of our data exploration and visualization tool GeoMapApp (www.geomapapp.org) includes a newly designed menu system with cascading and tear-off menus, a new Layer Manager that lists selected layers and enables re-ordering and rendering with variable transparency, a Go To option that allows direct zooming to areas of interest, and an Add Image Overlay option for importing georeferenced images. New data sets are continually added to both GeoMapApp and Virtual Ocean (www.virtualocean.org), a 3D virtual globe with GeoMapApp functionality. Several Ridge 2000 data sets are also bundled for viewing in Google Earth (www.marine-geo.org/tools/kmls.php). This poster will highlight new functionality and data sets relevant to Ridge 2000 Integration and Synthesis, and will provide comparisons of several data sets that exist for each ISS.

  4. Histones and genome integrity.

    Science.gov (United States)

    Williamson, Wes D; Pinto, Ines

    2012-01-01

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

  5. Video gallery of educational lectures integrated in faculty's portal

    Directory of Open Access Journals (Sweden)

    Jaroslav Majerník

    2013-05-01

    Full Text Available This paper presents a web based educational video-clips exhibition created to share various archived lectures for medical students, health care professionals as well as for general public. The presentation of closely related topics was developed as video gallery and it is based solely on free or open source tools to be available for wide academic and/or non-commercial use. Even if the educational video records can be embedded in any websites, we preferred to use our faculty’s portal, which should be a central point to offer various multimedia educational materials. The system was integrated and tested to offer open access to infectology lectures that were captured and archived from live-streamed sessions and from videoconferences.

  6. Integrated neutron/gamma-ray portal monitors for nuclear safeguards

    Science.gov (United States)

    Fehlau, Paul E.

    1994-08-01

    Radiation monitoring is one nuclear-safeguards measure used to protect against the theft of special nuclear materials (SNM) by pedestrians departing from SNM access areas. The integrated neutron/gamma-ray portal monitor is an ideal radiation monitor for the task when the SNM is plutonium. It achieves high sensitivity for detecting both bare and shielded plutonium by combining two types of radiation detector. One type is a neutron-chamber detector, comprising a large, hollow, neutron moderator that contains a single thermal-neutron proportional counter. The entrance wall of each chamber is thin to admit slow neutrons from plutonium contained in a moderating shield, while the other walls are thick to moderate fast neutrons from bare or lead-shielded plutonium so that they can be detected. The other type of detector is a plastic scintillator that is primarily for detecting gamma rays from small amounts of unshielded plutonium. The two types of detector are easily integrated by making scintillators part of the thick back wall of each neutron chamber or by inserting them into each chamber void. We compared the influence of the two methods of integration on detecting neutrons and gamma rays, and we examined the effectiveness of other design factors and the methods for signal detection as well.

  7. A customized Web portal for the genome of the ctenophore Mnemiopsis leidyi.

    Science.gov (United States)

    Moreland, R Travis; Nguyen, Anh-Dao; Ryan, Joseph F; Schnitzler, Christine E; Koch, Bernard J; Siewert, Katherine; Wolfsberg, Tyra G; Baxevanis, Andreas D

    2014-04-28

    Mnemiopsis leidyi is a ctenophore native to the coastal waters of the western Atlantic Ocean. A number of studies on Mnemiopsis have led to a better understanding of many key biological processes, and these studies have contributed to the emergence of Mnemiopsis as an important model for evolutionary and developmental studies. Recently, we sequenced, assembled, annotated, and performed a preliminary analysis on the 150-megabase genome of the ctenophore, Mnemiopsis. This sequencing effort has produced the first set of whole-genome sequencing data on any ctenophore species and is amongst the first wave of projects to sequence an animal genome de novo solely using next-generation sequencing technologies. The Mnemiopsis Genome Project Portal (http://research.nhgri.nih.gov/mnemiopsis/) is intended both as a resource for obtaining genomic information on Mnemiopsis through an intuitive and easy-to-use interface and as a model for developing customized Web portals that enable access to genomic data. The scope of data available through this Portal goes well beyond the sequence data available through GenBank, providing key biological information not available elsewhere, such as pathway and protein domain analyses; it also features a customized genome browser for data visualization. We expect that the availability of these data will allow investigators to advance their own research projects aimed at understanding phylogenetic diversity and the evolution of proteins that play a fundamental role in metazoan development. The overall approach taken in the development of this Web site can serve as a viable model for disseminating data from whole-genome sequencing projects, framed in a way that best-serves the specific needs of the scientific community.

  8. The Integrated Web Portal for Escalation with Overdose Control (EWOC).

    Science.gov (United States)

    Wang, Haibin; Tighiouart, Mourad; Huang, Shao-Chi; Berel, Dror; Cook-Wiens, Galen; Bresee, Catherine; Li, Quanlin; Rogatko, André

    2013-01-01

    In this paper, we present the design and implementation of a novel web portal for the cancer phase I clinical trial design method Escalation with Overdose Control (EWOC). The web portal has two major components: a web-based dose finding calculator; and a standalone and downloadable dose finding software which can be installed on Windows operating systems. The web-based dose finding calculator uses industry standards and is a database-driven and distributed computing platform for designing and conducting dose finding in cancer phase I clinical trials utilizing EWOC methodology. The web portal is developed using open source software: PHP, JQuery, R and OpenBUGS. It supports any standard browsers with internet connection. The web portal can be accessed at: http://biostatistics.csmc.edu.

  9. Probability landscapes for integrative genomics

    Directory of Open Access Journals (Sweden)

    Benecke Arndt

    2008-05-01

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

  10. Integrating BI Tools in an Enterprise Portal for a better Enterprise Management

    Directory of Open Access Journals (Sweden)

    Gianina MIHAI

    2014-09-01

    Full Text Available Access to information has always been a stringent necessity for any organization. This necessity has become more stringent in the actual economic context, as decisions must be taken in the shortest time. That is why, since the early sixties, Decision Support Systems emerged. They have evolved together with the client-server technology, during the eighties, towards today's Executive Support Systems. Nowadays, these systems tend to be replaced by Dashboards and Balanced Scorecards as individual BI tools or as integrated tools, which are part of more complex BI solutions, which fulfill the more and more sophisticated and growing information requirements from decision factors. In this paper, we shall present a partial integration solution of the BI tools in an enterprise portal created using Microsoft SharePoint Server technologies. Initially, the enterprise portal which we'll present in this paper was meant to be more a general solution for the informational integration of an organization and less than a portal with strong BI features. But, as we shall demonstrate by the means of this paper, the portal prototype, as it is now, can be rapidly expanded to an enterprise portal with full BI features.

  11. BioPortal: ontologies and integrated data resources at the click of a mouse.

    Science.gov (United States)

    Noy, Natalya F; Shah, Nigam H; Whetzel, Patricia L; Dai, Benjamin; Dorf, Michael; Griffith, Nicholas; Jonquet, Clement; Rubin, Daniel L; Storey, Margaret-Anne; Chute, Christopher G; Musen, Mark A

    2009-07-01

    Biomedical ontologies provide essential domain knowledge to drive data integration, information retrieval, data annotation, natural-language processing and decision support. BioPortal (http://bioportal.bioontology.org) is an open repository of biomedical ontologies that provides access via Web services and Web browsers to ontologies developed in OWL, RDF, OBO format and Protégé frames. BioPortal functionality includes the ability to browse, search and visualize ontologies. The Web interface also facilitates community-based participation in the evaluation and evolution of ontology content by providing features to add notes to ontology terms, mappings between terms and ontology reviews based on criteria such as usability, domain coverage, quality of content, and documentation and support. BioPortal also enables integrated search of biomedical data resources such as the Gene Expression Omnibus (GEO), ClinicalTrials.gov, and ArrayExpress, through the annotation and indexing of these resources with ontologies in BioPortal. Thus, BioPortal not only provides investigators, clinicians, and developers 'one-stop shopping' to programmatically access biomedical ontologies, but also provides support to integrate data from a variety of biomedical resources.

  12. Integrating social media tools in a web portal

    OpenAIRE

    Santos, Daniela; Picoto, Winnie

    2013-01-01

    Benefitting from Web 2.0 features, Social Media allows organisations to be where the users are, creating proximity, talking to them, and knowing what they want. Going viral and word-of-mouth become easier, as these platforms allow us to share, to like, and to use multimedia and convergence – as they can interact with each other, communicating on a large scale. Given that online portals provide for a highly competitive environment, players strive to get more visits, better search rankings, and...

  13. Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation

    Energy Technology Data Exchange (ETDEWEB)

    Lokareddy, Ravi K.; Sankhala, Rajeshwer S.; Roy, Ankoor; Afonine, Pavel V.; Motwani, Tina; Teschke, Carolyn M.; Parent, Kristin N.; Cingolani, Gino (Rutgers); (LBNL); (Connecticut); (TJU); (MSU)

    2017-01-30

    Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid’) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging’ is a DNA-dependent symmetrization of portal protein.

  14. 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.

  15. Extending Interactive Web Services for Improving Presentation Level Integration in Web Portals

    Institute of Scientific and Technical Information of China (English)

    Jing-Yu Song; Jun Wei; Shu-Chao Wan; Tao Huang

    2006-01-01

    Presentation level integration now becomes an important and fast growing trend in enterprise computing.Portal-based composite applications use portlet and interactive web service, which usually offers several portlets, as their basic constituents. Hence, portlet description and discovery are the key issues that have to be considered for the development of portal-based composite applications. This paper proposes a novel concept POI (Presentation Oriented Interface) to describe the presentation features of a portlet, so that interactive web services may be extended to facilitate the selection and interoperation of portlets. Portlet discovery can be effectively achieved based on the calculation of POI similarity that considers both type and structure similarity. Experiments show that the proposed approach can improve the satisfaction of portlet discovery, and also facilitate the portlet interoperation, thereby achieving better application integration at presentation level.

  16. Integrated genome browser: visual analytics platform for genomics

    OpenAIRE

    2016-01-01

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

  17. Integrating thematic web portal capabilities into the NASA Earthdata Web Infrastructure

    Science.gov (United States)

    Wong, M. M.; McLaughlin, B. D.; Huang, T.; Baynes, K.

    2015-12-01

    The National Aeronautics and Space Administration (NASA) acquires and distributes an abundance of Earth science data on a daily basis to a diverse user community worldwide. To assist the scientific community and general public in achieving a greater understanding of the interdisciplinary nature of Earth science and of key environmental and climate change topics, the NASA Earthdata web infrastructure is integrating new methods of presenting and providing access to Earth science information, data, research and results. This poster will present the process of integrating thematic web portal capabilities into the NASA Earthdata web infrastructure, with examples from the Sea Level Change Portal. The Sea Level Change Portal will be a source of current NASA research, data and information regarding sea level change. The portal will provide sea level change information through articles, graphics, videos and animations, an interactive tool to view and access sea level change data and a dashboard showing sea level change indicators. Earthdata is a part of the Earth Observing System Data and Information System (EOSDIS) project. EOSDIS is a key core capability in NASA's Earth Science Data Systems Program. It provides end-to-end capabilities for managing NASA's Earth science data from various sources - satellites, aircraft, field measurements, and various other programs. It is comprised of twelve Distributed Active Archive Centers (DAACs), Science Computing Facilities (SCFs), data discovery and service access client (Reverb and Earthdata Search), dataset directory (Global Change Master Directory - GCMD), near real-time data (Land Atmosphere Near real-time Capability for EOS - LANCE), Worldview (an imagery visualization interface), Global Imagery Browse Services, the Earthdata Code Collaborative and a host of other discipline specific data discovery, data access, data subsetting and visualization tools.

  18. The Integrate Student Portal: Online Resources to Prepare Students for the Workforce of a Sustainable Future

    Science.gov (United States)

    Bruckner, M. Z.; Manduca, C. A.; Egger, A. E.; Macdonald, H.

    2014-12-01

    The InTeGrate Student Portal is a suite of web pages that utilize InTeGrate resources to support student success by providing undergraduates with tools and information necessary to be proactive in their career choices and development. Drawn from various InTeGrate workshops and programming, the Portal organizes these resources to illuminate a variety of career opportunities and pathways to both traditional and non-traditional jobs that support a sustainable future. Informed from a variety of sources including employers, practitioners, faculty, students, reports, and articles, the pages explore five facets: (1) sustainability across the disciplines, (2) workforce preparation, (3) professional communication, (4) teaching and teaching careers, and (5) the future of green research and technology. The first three facets explore how sustainability is integrated across disciplines and how sustainability and 'green' jobs are available in a wide range of traditional and non-traditional workplaces within and beyond science. They provide students guidance in preparing for this sustainability workforce, including where to learn about jobs and how to pursue them, advice for strengthening their job applications, and how to build a set of skills that employers seek. This advice encompasses classroom skills as well as those acquired and strengthened as part of extracurricular or workplace experiences. The fourth facet, aimed at teaching assistants with little or no experience as well as at students who are interested in pursuing teaching as a career, provides information and resources about teaching. The fifth facet explores future directions of technology and the need for innovations in the workforce of the future to address sustainability issues. We seek your input and invite you to explore the Portal at: serc.carleton.edu/integrate/students/

  19. Promoting scientific collaboration and research through integrated social networking capabilities within the OpenTopography Portal

    Science.gov (United States)

    Nandigam, V.; Crosby, C. J.; Baru, C.

    2009-04-01

    LiDAR (Light Distance And Ranging) topography data offer earth scientists the opportunity to study the earth's surface at very high resolutions. As a result, the popularity of these data is growing dramatically. However, the management, distribution, and analysis of community LiDAR data sets is a challenge due to their massive size (multi-billion point, mutli-terabyte). We have also found that many earth science users of these data sets lack the computing resources and expertise required to process these data. We have developed the OpenTopography Portal to democratize access to these large and computationally challenging data sets. The OpenTopography Portal uses cyberinfrastructure technology developed by the GEON project to provide access to LiDAR data in a variety of formats. LiDAR data products available range from simple Google Earth visualizations of LiDAR-derived hillshades to 1 km2 tiles of standard digital elevation model (DEM) products as well as LiDAR point cloud data and user generated custom-DEMs. We have found that the wide spectrum of LiDAR users have variable scientific applications, computing resources and technical experience and thus require a data system with multiple distribution mechanisms and platforms to serve a broader range of user communities. Because the volume of LiDAR topography data available is rapidly expanding, and data analysis techniques are evolving, there is a need for the user community to be able to communicate and interact to share knowledge and experiences. To address this need, the OpenTopography Portal enables social networking capabilities through a variety of collaboration tools, web 2.0 technologies and customized usage pattern tracking. Fundamentally, these tools offer users the ability to communicate, to access and share documents, participate in discussions, and to keep up to date on upcoming events and emerging technologies. The OpenTopography portal achieves the social networking capabilities by integrating various

  20. Integrating genome assemblies with MAIA

    NARCIS (Netherlands)

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

    2010-01-01

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

  1. A Web Service Based Design to Integrate a Web Portal and an ERP System

    Directory of Open Access Journals (Sweden)

    Mr. Manishkumar R. Solanki

    2014-04-01

    Full Text Available Today the ability to seamlessly exchange information between internal business processes, customers, and partners is vital for success. The organizations employ a variety of disparate applications that store and exchange data in dissimilar ways and therefore cannot "talk" to one another productively. Web services have evolved as a practical, cost-effective, deployment environment to realize dynamic and interoperable data integration between critical applications over operating system, platform, and language barriers that were previously impossible. This paper describes a service-oriented approach for the integration of a Web Portal and ERP application. We present a system architecture based on Web Service oriented framework in which both the applications are loosely connected through software components.

  2. An integrated healthcare enterprise information portal and healthcare information system framework.

    Science.gov (United States)

    Hsieh, S L; Lai, Feipei; Cheng, P H; Chen, J L; Lee, H H; Tsai, W N; Weng, Y C; Hsieh, S H; Hsu, K P; Ko, L F; Yang, T H; Chen, C H

    2006-01-01

    The paper presents an integrated, distributed Healthcare Enterprise Information Portal (HEIP) and Hospital Information Systems (HIS) framework over wireless/wired infrastructure at National Taiwan University Hospital (NTUH). A single sign-on solution for the hospital customer relationship management (CRM) in HEIP has been established. The outcomes of the newly developed Outpatient Information Systems (OIS) in HIS are discussed. The future HEIP blueprints with CRM oriented features: e-Learning, Remote Consultation and Diagnosis (RCD), as well as on-Line Vaccination Services are addressed. Finally, the integrated HEIP and HIS architectures based on the middleware technologies are proposed along with the feasible approaches. The preliminary performance of multi-media, time-based data exchanges over the wireless HEIP side is collected to evaluate the efficiency of the architecture.

  3. 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.

  4. Integrative bayesian network analysis of genomic data.

    Science.gov (United States)

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

    2014-01-01

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

  5. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

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

  6. Patient portals : Development and outcomes in integrated and fragmented health systems

    NARCIS (Netherlands)

    E.T. Otte-Trojel (Eva Terese)

    2015-01-01

    markdownabstractPatient portals can give patients access to a personal health record and enable interaction with the health care system. Patient portals are creating unprecedented opportunities for using health IT to deliver care to patients, paving the way for benefits to patients, providers and th

  7. Patient portals : Development and outcomes in integrated and fragmented health systems

    NARCIS (Netherlands)

    E.T. Otte-Trojel (Eva Terese)

    2015-01-01

    markdownabstractPatient portals can give patients access to a personal health record and enable interaction with the health care system. Patient portals are creating unprecedented opportunities for using health IT to deliver care to patients, paving the way for benefits to patients, providers and

  8. Integrative Genomics and Computational Systems Medicine

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

  9. Integration of GFDL Data Portal into FMS Runtime Environment (FRE) modeling framework

    Science.gov (United States)

    Nikonov, S.; Balaji, V.; Rehbein, C.; Malysheva, Y.

    2009-12-01

    The complexities of modern climate modeling and the tremendous volume of model output data require advancements in the development of a climate model data dissemination infrastructure, stressing tight integration with the modeling framework. It is particularly important on the threshold of the IPCC Assessment Report 5, where data volume growth is expected to be two orders of magnitude beyond what was required for AR4. Shared infrastructure between the modeling framework and the data preparation and publishing framework will more easily allow the automation of three important phases of data dissemination: - Proper metadata annotation of datasets, including but not limited to model principles, configurations and simulation details; - Making data available using community-adopted standards; - Web-based data publishing which can feature semantic discoverability, navigation, federalization and analysis of published datasets. A framework which integrates the running of models with the publishing of data is a mutually profitable process. Climate model authors would have a powerful tool for composing and analyzing conducted experiments using FRE and a well-organized metadata database. In turn, those maintaining the data access portal gain direct access to metadata used in FMS that is useful in the process of publishing data. The kernel of this integration is a model development database that contains metadata describing all aspects of the modeling process, ranging from model configuration through model runtime, including model output analysis and data publishing. The database is populated using an automated process that collects model information and metadata via the model's XML-based configuration file. The framework also allows one to work backwards, generating synthesized experiment configurations using experiment components established in prior conducted experiments. In addition, a web-based graphical interface grants the model author a friendly and comfortable way to

  10. Integrating continental-scale ecological data into university courses: Developing NEON's Online Learning Portal

    Science.gov (United States)

    Wasser, L. A.; Gram, W.; Lunch, C. K.; Petroy, S. B.; Elmendorf, S.

    2013-12-01

    'Big Data' are becoming increasingly common in many fields. The National Ecological Observatory Network (NEON) will be collecting data over the 30 years, using consistent, standardized methods across the United States. Similar efforts are underway in other parts of the globe (e.g. Australia's Terrestrial Ecosystem Research Network, TERN). These freely available new data provide an opportunity for increased understanding of continental- and global scale processes such as changes in vegetation structure and condition, biodiversity and landuse. However, while 'big data' are becoming more accessible and available, integrating big data into the university courses is challenging. New and potentially unfamiliar data types and associated processing methods, required to work with a growing diversity of available data, may warrant time and resources that present a barrier to classroom integration. Analysis of these big datasets may further present a challenge given large file sizes, and uncertainty regarding best methods to properly statistically summarize and analyze results. Finally, teaching resources, in the form of demonstrative illustrations, and other supporting media that might help teach key data concepts, take time to find and more time to develop. Available resources are often spread widely across multi-online spaces. This presentation will overview the development of NEON's collaborative University-focused online education portal. Portal content will include 1) interactive, online multi-media content that explains key concepts related to NEON's data products including collection methods, key metadata to consider and consideration of potential error and uncertainty surrounding data analysis; and 2) packaged 'lab' activities that include supporting data to be used in an ecology, biology or earth science classroom. To facilitate broad use in classrooms, lab activities will take advantage of freely and commonly available processing tools, techniques and scripts. All

  11. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system.

    Science.gov (United States)

    Sunkin, Susan M; Ng, Lydia; Lau, Chris; Dolbeare, Tim; Gilbert, Terri L; Thompson, Carol L; Hawrylycz, Michael; Dang, Chinh

    2013-01-01

    The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.

  12. Portal Hypertension

    Science.gov (United States)

    ... Obesity to Liver Cancer Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD, Thomas Jefferson ... Liver Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension (See also Overview of Liver Disease .) Portal ...

  13. DECADE Web Portal: Integrating MaGa, EarthChem and GVP Will Further Our Knowledge on Earth Degassing

    Science.gov (United States)

    Cardellini, C.; Frigeri, A.; Lehnert, K. A.; Ash, J.; McCormick, B.; Chiodini, G.; Fischer, T. P.; Cottrell, E.

    2014-12-01

    The release of gases from the Earth's interior to the exosphere takes place in both volcanic and non-volcanic areas of the planet. Fully understanding this complex process requires the integration of geochemical, petrological and volcanological data. At present, major online data repositories relevant to studies of degassing are not linked and interoperable. We are developing interoperability between three of those, which will support more powerful synoptic studies of degassing. The three data systems that will make their data accessible via the DECADE portal are: (1) the Smithsonian Institution's Global Volcanism Program database (GVP) of volcanic activity data, (2) EarthChem databases for geochemical and geochronological data of rocks and melt inclusions, and (3) the MaGa database (Mapping Gas emissions) which contains compositional and flux data of gases released at volcanic and non-volcanic degassing sites. These databases are developed and maintained by institutions or groups of experts in a specific field, and data are archived in formats specific to these databases. In the framework of the Deep Earth Carbon Degassing (DECADE) initiative of the Deep Carbon Observatory (DCO), we are developing a web portal that will create a powerful search engine of these databases from a single entry point. The portal will return comprehensive multi-component datasets, based on the search criteria selected by the user. For example, a single geographic or temporal search will return data relating to compositions of emitted gases and erupted products, the age of the erupted products, and coincident activity at the volcano. The development of this level of capability for the DECADE Portal requires complete synergy between these databases, including availability of standard-based web services (WMS, WFS) at all data systems. Data and metadata can thus be extracted from each system without interfering with each database's local schema or being replicated to achieve integration at

  14. Verifying 4D gated radiotherapy using time-integrated electronic portal imaging: a phantom and clinical study

    Directory of Open Access Journals (Sweden)

    Slotman Ben J

    2007-08-01

    Full Text Available Abstract Background Respiration-gated radiotherapy (RGRT can decrease treatment toxicity by allowing for smaller treatment volumes for mobile tumors. RGRT is commonly performed using external surrogates of tumor motion. We describe the use of time-integrated electronic portal imaging (TI-EPI to verify the position of internal structures during RGRT delivery Methods TI-EPI portals were generated by continuously collecting exit dose data (aSi500 EPID, Portal vision, Varian Medical Systems when a respiratory motion phantom was irradiated during expiration, inspiration and free breathing phases. RGRT was delivered using the Varian RPM system, and grey value profile plots over a fixed trajectory were used to study object positions. Time-related positional information was derived by subtracting grey values from TI-EPI portals sharing the pixel matrix. TI-EPI portals were also collected in 2 patients undergoing RPM-triggered RGRT for a lung and hepatic tumor (with fiducial markers, and corresponding planning 4-dimensional CT (4DCT scans were analyzed for motion amplitude. Results Integral grey values of phantom TI-EPI portals correlated well with mean object position in all respiratory phases. Cranio-caudal motion of internal structures ranged from 17.5–20.0 mm on planning 4DCT scans. TI-EPI of bronchial images reproduced with a mean value of 5.3 mm (1 SD 3.0 mm located cranial to planned position. Mean hepatic fiducial markers reproduced with 3.2 mm (SD 2.2 mm caudal to planned position. After bony alignment to exclude set-up errors, mean displacement in the two structures was 2.8 mm and 1.4 mm, respectively, and corresponding reproducibility in anatomy improved to 1.6 mm (1 SD. Conclusion TI-EPI appears to be a promising method for verifying delivery of RGRT. The RPM system was a good indirect surrogate of internal anatomy, but use of TI-EPI allowed for a direct link between anatomy and breathing patterns.

  15. Description and testing of the Geo Data Portal: Data integration framework and Web processing services for environmental science collaboration

    Science.gov (United States)

    Blodgett, David L.; Booth, Nathaniel L.; Kunicki, Thomas C.; Walker, Jordan I.; Viger, Roland J.

    2011-01-01

    Interest in sharing interdisciplinary environmental modeling results and related data is increasing among scientists. The U.S. Geological Survey Geo Data Portal project enables data sharing by assembling open-standard Web services into an integrated data retrieval and analysis Web application design methodology that streamlines time-consuming and resource-intensive data management tasks. Data-serving Web services allow Web-based processing services to access Internet-available data sources. The Web processing services developed for the project create commonly needed derivatives of data in numerous formats. Coordinate reference system manipulation and spatial statistics calculation components implemented for the Web processing services were confirmed using ArcGIS 9.3.1, a geographic information science software package. Outcomes of the Geo Data Portal project support the rapid development of user interfaces for accessing and manipulating environmental data.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kyrpides, Nikos C.; Markowitz, Victor M.

    2006-03-01

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

  19. Mitochondrial Genome Deletion for Detection of Prostate Cancer — EDRN Public Portal

    Science.gov (United States)

    The Prostate Core Mitomic Test™ is based upon a 3.4 kb mitochondrial genome deletion (3.4 mtdelta) that was identified through PCR analysis of frozen prostate cancer samples. In cancer research it has been found that deletions in mitochondrial DNA can correlate with cellular changes that indicate development of cancer. This deletion includes the terminal 22 bases of MT-ND4L, all of MT-ND4, 3 tRNAs (histidine, serine 2, and leucine 2), and all except the terminal 24 bases of MT-ND5.

  20. ASKME Enterprise Portal (internal) -

    Data.gov (United States)

    Department of Transportation — The ASKME Enterprise Portal Internal (AEPi) is envisioned to be an integrated, single-point-of-entry solution that contains modular components. The AEPi will provide...

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

    Science.gov (United States)

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

    2014-11-01

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

  2. Remote Sensing, New Media and Scientific Literacy for Competence Oriented School Education - A New Integrated Learning Portal

    Science.gov (United States)

    Hodam, H.; Goetzke, R.; Rinow, A.; Voß, K.

    2012-04-01

    The project FIS - Fernerkundung in Schulen (German for "Remote Sensing in Schools") - aims at a better integration of remote sensing in school lessons. Respectively, the overall ob-jective is to teach pupils from primary school up to high-school graduation basics and fields of application of remote sensing. Working with remote sensing data opens up new and modern ways of teaching. Therefore many teachers have great interest in the subject "remote sensing", being motivated to integrate this topic into teaching, provided that the curriculum is con-sidered. In many cases, this encouragement fails because of confusing information, which ruins all good intentions. For this reason, a comprehensive and well structured learning portal on the subject remote sensing is developed. This will allow teachers and pupils to have a structured initial understanding of the topic. Recognizing that in-depth use of satellite imagery can only be achieved by the means of computer aided learning methods, a sizeable number of e-Learning contents have been created throughout the last 5 years since the project's kickoff which are now integrated into the learning portal. Three main sections form the backbone of the developed learning portal. 1. The "Teaching Materials" section provides registered teachers with interactive lessons to convey curriculum relevant topics through remote sensing. They are able to use the implemented management system to create classes and enregister pupils, keep track of their progresses and control results of the conducted lessons. Abandoning the functio-nalities of the management system the lessons are also available to non-registered us-ers. 2. Pupils and Teachers can investigate further into remote sensing in the "Research" sec-tion, where a knowledge base alongside a satellite image gallery offer general back-ground information on remote sensing and the provided lessons in a semi interactive manner. 3. The "Analysis Tools" section offers means to further

  3. 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.

  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. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jizhong; He, Zhili

    2014-04-08

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

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

    Science.gov (United States)

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

    2011-07-01

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

  8. Portal Vein Thrombosis

    OpenAIRE

    Hakan Demirci

    2016-01-01

    Portal vein thrombosis is an important cause of presinusoidal portal hypertension. Portal vein thrombosis commonly occurs in patient with cirrhosis, malignancy and prothrombotic states. Patients with acute portal vein thrombosis have immediate onset. Patients with chronic portal vein thrombosis have developed portal hypertension and cavernous portal transformation. Portal vein thrombosis is diagnosed with doppler ultrasound, computed tomography and magnetic resonance imaging. Therapy with low...

  9. Integration of genomics in cancer care

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  10. Integrated genomic analyses of ovarian carcinoma

    NARCIS (Netherlands)

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

    2011-01-01

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

  11. Dictionary Portals

    NARCIS (Netherlands)

    Sijens, H.; Dykstra, A.; Boelhouwer, Bob; Fuertes-Olivera, Pedro A.

    2016-01-01

    Web portals have been one of the first web services that have helped users to find the information they need in the ever expanding World Wide Web. A web portal is basically a website that groups links to information available on the web. These links are selected based on certain criteria. Some web p

  12. Dictionary Portals

    NARCIS (Netherlands)

    Sijens, H.; Dykstra, A.; Boelhouwer, Bob; Fuertes-Olivera, Pedro A.

    2016-01-01

    Web portals have been one of the first web services that have helped users to find the information they need in the ever expanding World Wide Web. A web portal is basically a website that groups links to information available on the web. These links are selected based on certain criteria. Some web

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

    Science.gov (United States)

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

    2015-05-01

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

  14. STINGRAY: system for integrated genomic resources and analysis

    OpenAIRE

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

    2014-01-01

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

  15. Defining nephrotic syndrome from an integrative genomics perspective.

    Science.gov (United States)

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

    2015-01-01

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

  16. Prototype of an Integrated Hurricane Information System for Research: Design and Implementation of the Database and Web Portal

    Science.gov (United States)

    Li, P. P.; Knosp, B.; Vu, Q. A.; Hristova-Veleva, S.; Chao, Y.; Vane, D.; Lambrigtsen, B.; Su, H.; Dang, V.; Fovell, R.; Willis, J.; Tanelli, S.; Fishbein, E.; Ao, C. O.; Poulsen, W. L.; Park, K. J.; Fetzer, E.; Vazquez, J.; Callahan, P. S.; Marcus, S.; Garay, M.; Kahn, R.; Haddad, Z.

    2007-12-01

    Many hurricane websites provide historical hurricane information and real-time storm tracking. These sites often include images from various remote-sensing satellite sensors with such atmospheric and oceanic quantities as wind, temperature, rain, and water vapor. However, it has been determined that the hurricane analysis community is lacking a web portal that provides researchers a comprehensive set of observed hurricane parameters (both graphics and data) together with large-scale and convection-resolving model output. We have developed a prototype of an integrated hurricane information system of high-resolution satellite and in- situ observations along with model outputs pertaining to: i) the thermodynamic and microphysical structure of storms; ii) the air-sea interaction processes; iii) the larger-scale environment as depicted by quantities such as SST, ocean heat content and the aerosol loading of the environment. Our goal is to provide a one-stop place to access all the available information of a specific hurricane for researchers to advance the understanding, modeling and predication of hurricane genesis and intensity changes. Our hurricane information system prototype consists of high-resolution satellite data measuring three- dimensional atmospheric and oceanic parameters that includes observations from AIRS, MISR, MODIS, CloudSAT, AMSR-E, TRMM, GOES, MLS, QuikSCAT, SeaWiFS, and COSMIC GPS, in-situ observations such as ARGO floats, large scale data assimilation products from NCEP, and high resolution hurricane model output from WRF. High-resolution satellite data are sub-setted within 2000-kilometer-square area centered at the closest storm location and large-scale environmental datasets are divided into 6 predefined geographical regions. When accessing this hurricane portal, users may browse through data by year, region, category, and hurricane. At the front page, we show the hurricane track using Google Map. Users may pan and zoom, or click on the track

  17. Integrative modules for efficient genome engineering in yeast

    Directory of Open Access Journals (Sweden)

    Triana Amen

    2017-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-12-01

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

  1. 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/.

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

    Directory of Open Access Journals (Sweden)

    Jung Kyongyong

    2009-04-01

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

  3. 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.

  4. 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

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

    Science.gov (United States)

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

    2015-06-01

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

  6. Description of the U.S. Geological Survey Geo Data Portal data integration framework

    Science.gov (United States)

    Blodgett, David L.; Booth, Nathaniel L.; Kunicki, Thomas C.; Walker, Jordan I.; Lucido, Jessica M.

    2012-01-01

    The U.S. Geological Survey has developed an open-standard data integration framework for working efficiently and effectively with large collections of climate and other geoscience data. A web interface accesses catalog datasets to find data services. Data resources can then be rendered for mapping and dataset metadata are derived directly from these web services. Algorithm configuration and information needed to retrieve data for processing are passed to a server where all large-volume data access and manipulation takes place. The data integration strategy described here was implemented by leveraging existing free and open source software. Details of the software used are omitted; rather, emphasis is placed on how open-standard web services and data encodings can be used in an architecture that integrates common geographic and atmospheric data.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. GEO portal

    Data.gov (United States)

    US Agency for International Development — The USAID GeoPortal is a new application that groups web-based capabilities for on-demand discovery of and access to geospatial content, services, expertise, and...

  9. Portal biliopathy.

    Science.gov (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-21

    Portal biliopathy refers to cholangiographic abnormalities which occur in patients with portal cavernoma. These changes occur as a result of pressure on bile ducts from bridging tortuous paracholedochal, epicholedochal and cholecystic veins. Bile duct ischemia may occur due prolonged venous pressure effect or result from insufficient blood supply. In addition, encasement of ducts may occur due fibrotic cavernoma. Majority of patients are asymptomatic. Portal biliopathy is a progressive disease and patients who have long standing disease and more severe bile duct abnormalities present with recurrent episodes of biliary pain, cholangitis and cholestasis. Serum chemistry, ultrasound with color Doppler imaging, magnetic resonance imaging with magnetic resonance cholangiopancreatography and magnetic resonance portovenography are modalities of choice for evaluation of portal biliopathy. Endoscopic retrograde cholangiography being an invasive procedure is indicated for endotherapy only. Management of portal biliopathy is done in a stepwise manner. First, endotherapy is done for dilation of biliary strictures, placement of biliary stents to facilitate drainage and removal of bile duct calculi. Next portal venous pressure is reduced by formation of surgical porto-systemic shunt or transjugular intrahepatic portosystemic shunt. This causes significant resolution of biliary changes. Patients who persist with biliary symptoms and bile duct changes may benefit from surgical biliary drainage procedures (hepaticojejunostomy or choledechoduodenostomy).

  10. Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study

    Science.gov (United States)

    Wolfs, Cecile J. A.; Brás, Mariana G.; Schyns, Lotte E. J. R.; Nijsten, Sebastiaan M. J. J. G.; van Elmpt, Wouter; Scheib, Stefan G.; Baltes, Christof; Podesta, Mark; Verhaegen, Frank

    2017-08-01

    The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

  11. A Cloud-enabled Service-oriented Spatial Web Portal for Facilitating Arctic Data Discovery, Integration, and Utilization

    Science.gov (United States)

    dias, S. B.; Yang, C.; Li, Z.; XIA, J.; Liu, K.; Gui, Z.; Li, W.

    2013-12-01

    Global climate change has become one of the biggest concerns for human kind in the 21st century due to its broad impacts on society and ecosystems across the world. Arctic has been observed as one of the most vulnerable regions to the climate change. In order to understand the impacts of climate change on the natural environment, ecosystems, biodiversity and others in the Arctic region, and thus to better support the planning and decision making process, cross-disciplinary researches are required to monitor and analyze changes of Arctic regions such as water, sea level, biodiversity and so on. Conducting such research demands the efficient utilization of various geospatially referenced data, web services and information related to Arctic region. In this paper, we propose a cloud-enabled and service-oriented Spatial Web Portal (SWP) to support the discovery, integration and utilization of Arctic related geospatial resources, serving as a building block of polar CI. This SWP leverages the following techniques: 1) a hybrid searching mechanism combining centralized local search, distributed catalogue search and specialized Internet search for effectively discovering Arctic data and web services from multiple sources; 2) a service-oriented quality-enabled framework for seamless integration and utilization of various geospatial resources; and 3) a cloud-enabled parallel spatial index building approach to facilitate near-real time resource indexing and searching. A proof-of-concept prototype is developed to demonstrate the feasibility of the proposed SWP, using an example of analyzing the Arctic snow cover change over the past 50 years.

  12. Time-resolved versus time-integrated portal dosimetry: the role of an object's position with respect to the isocenter in volumetric modulated arc therapy.

    Science.gov (United States)

    Schyns, Lotte E J R; Persoon, Lucas C G G; Podesta, Mark; van Elmpt, Wouter J C; Verhaegen, Frank

    2016-05-21

    The aim of this work is to compare time-resolved (TR) and time-integrated (TI) portal dosimetry, focussing on the role of an object's position with respect to the isocenter in volumetric modulated arc therapy (VMAT). Portal dose images (PDIs) are simulated and measured for different cases: a sphere (1), a bovine bone (2) and a patient geometry (3). For the simulated case (1) and the experimental case (2), several transformations are applied at different off-axis positions. In the patient case (3), three simple plans with different isocenters are created and pleural effusion is simulated in the patient. The PDIs before and after the sphere transformations, as well as the PDIs with and without simulated pleural effusion, are compared using a TI and TR gamma analysis. In addition, the performance of the TI and TR gamma analyses for the detection of real geometric changes in patients treated with clinical plans is investigated and a correlation analysis is performed between gamma fail rates and differences in dose volume histogram (DVH) metrics. The TI gamma analysis can show large differences in gamma fail rates for the same transformation at different off-axis positions (or for different plan isocenters). The TR gamma analysis, however, shows consistent gamma fail rates. For the detection of real geometric changes in patients treated with clinical plans, the TR gamma analysis has a higher sensitivity than the TI gamma analysis. However, the specificity for the TR gamma analysis is lower than for the TI gamma analysis. Both the TI and TR gamma fail rates show no correlation with changes in DVH metrics. This work shows that TR portal dosimetry is fundamentally superior to TI portal dosimetry, because it removes the strong dependence of the gamma fail rate on the off-axis position/plan isocenter. However, for 2D TR portal dosimetry, it is still difficult to interpret gamma fail rates in terms of changes in DVH metrics for patients treated with VMAT.

  13. Time-resolved versus time-integrated portal dosimetry: the role of an object’s position with respect to the isocenter in volumetric modulated arc therapy

    Science.gov (United States)

    Schyns, Lotte E. J. R.; Persoon, Lucas C. G. G.; Podesta, Mark; van Elmpt, Wouter J. C.; Verhaegen, Frank

    2016-05-01

    The aim of this work is to compare time-resolved (TR) and time-integrated (TI) portal dosimetry, focussing on the role of an object’s position with respect to the isocenter in volumetric modulated arc therapy (VMAT). Portal dose images (PDIs) are simulated and measured for different cases: a sphere (1), a bovine bone (2) and a patient geometry (3). For the simulated case (1) and the experimental case (2), several transformations are applied at different off-axis positions. In the patient case (3), three simple plans with different isocenters are created and pleural effusion is simulated in the patient. The PDIs before and after the sphere transformations, as well as the PDIs with and without simulated pleural effusion, are compared using a TI and TR gamma analysis. In addition, the performance of the TI and TR gamma analyses for the detection of real geometric changes in patients treated with clinical plans is investigated and a correlation analysis is performed between gamma fail rates and differences in dose volume histogram (DVH) metrics. The TI gamma analysis can show large differences in gamma fail rates for the same transformation at different off-axis positions (or for different plan isocenters). The TR gamma analysis, however, shows consistent gamma fail rates. For the detection of real geometric changes in patients treated with clinical plans, the TR gamma analysis has a higher sensitivity than the TI gamma analysis. However, the specificity for the TR gamma analysis is lower than for the TI gamma analysis. Both the TI and TR gamma fail rates show no correlation with changes in DVH metrics. This work shows that TR portal dosimetry is fundamentally superior to TI portal dosimetry, because it removes the strong dependence of the gamma fail rate on the off-axis position/plan isocenter. However, for 2D TR portal dosimetry, it is still difficult to interpret gamma fail rates in terms of changes in DVH metrics for patients treated with VMAT.

  14. Integrative pathway genomics of lung function and airflow obstruction

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

  16. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

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

  17. 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

  18. 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

  19. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

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

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

    Science.gov (United States)

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

    2017-03-01

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

  1. MAKOCI: A WEB PORTAL FOR INTEGRATING AND SHARING GEOGRAPHIC INFORMATION SERVICES

    Directory of Open Access Journals (Sweden)

    Chin-Te Jung

    2013-01-01

    Full Text Available The lack of integration and communication of various geographic information services (GI services has resulted in many duplication collection of earth observation data, and challenges of semantic interoperability. This paper proposes an ontology-based multi-agents platform, called MAKOCI (multi-agent knowledge oriented cyberinfrastructure, which acts as GI service one stop to manage, publish, share, and discover GI services semantically. By ontologies, formal meanings of concepts are defined to annotate and discover GI services on a conceptual level for semantic interoperability. With the assistance of multi-agents, the processes in MAKOCI can be divided into various modules and be communicated based on the same semantics in ontologies. A prototype was implemented to test MAKOCI. Finally, we conclude the advantages and disadvantages of MAKOCI and point out several future works.

  2. Genomic Encyclopedia of Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  3. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  4. DemaDb: an integrated dematiaceous fungal genomes database.

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huseyin Tas

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  7. ASH External Web Portal (External Portal) -

    Data.gov (United States)

    Department of Transportation — The ASH External Web Portal is a web-based portal that provides single sign-on functionality, making the web portal a single location from which to be authenticated...

  8. DECADE web portal: toward the integration of MaGa, EarthChem and VOTW data systems to further the knowledge on Earth degassing

    Science.gov (United States)

    Cardellini, Carlo; Frigeri, Alessandro; Lehnert, Kerstin; Ash, Jason; McCormick, Brendan; Chiodini, Giovanni; Fischer, Tobias; Cottrell, Elizabeth

    2015-04-01

    The release of volatiles from the Earth's interior takes place in both volcanic and non-volcanic areas of the planet. The comprehension of such complex process and the improvement of the current estimates of global carbon emissions, will greatly benefit from the integration of geochemical, petrological and volcanological data. At present, major online data repositories relevant to studies of degassing are not linked and interoperable. In the framework of the Deep Earth Carbon Degassing (DECADE) initiative of the Deep Carbon Observatory (DCO), we are developing interoperability between three data systems that will make their data accessible via the DECADE portal: (1) the Smithsonian Institutionian's Global Volcanism Program database (VOTW) of volcanic activity data, (2) EarthChem databases for geochemical and geochronological data of rocks and melt inclusions, and (3) the MaGa database (Mapping Gas emissions) which contains compositional and flux data of gases released at volcanic and non-volcanic degassing sites. The DECADE web portal will create a powerful search engine of these databases from a single entry point and will return comprehensive multi-component datasets. A user will be able, for example, to obtain data relating to compositions of emitted gases, compositions and age of the erupted products and coincident activity, of a specific volcano. This level of capability requires a complete synergy between the databases, including availability of standard-based web services (WMS, WFS) at all data systems. Data and metadata can thus be extracted from each system without interfering with each database's local schema or being replicated to achieve integration at the DECADE web portal. The DECADE portal will enable new synoptic perspectives on the Earth degassing process allowing to explore Earth degassing related datasets over previously unexplored spatial or temporal ranges.

  9. Portal Vein Thrombosis

    Directory of Open Access Journals (Sweden)

    Hakan Demirci

    2016-01-01

    Full Text Available Portal vein thrombosis is an important cause of presinusoidal portal hypertension. Portal vein thrombosis commonly occurs in patient with cirrhosis, malignancy and prothrombotic states. Patients with acute portal vein thrombosis have immediate onset. Patients with chronic portal vein thrombosis have developed portal hypertension and cavernous portal transformation. Portal vein thrombosis is diagnosed with doppler ultrasound, computed tomography and magnetic resonance imaging. Therapy with low molecular weight heparin achieves recanalization in more than half of acute cases.

  10. Integrated genomic analysis of breast cancers.

    Science.gov (United States)

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

    2012-12-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

    Castrillo, Juan I; Oliver, Stephen G

    2004-01-31

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

  14. 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.

  15. The Einstein Genome Gateway using WASP - a high throughput multi-layered life sciences portal for XSEDE.

    Science.gov (United States)

    Golden, Aaron; McLellan, Andrew S; Dubin, Robert A; Jing, Qiang; O Broin, Pilib; Moskowitz, David; Zhang, Zhengdong; Suzuki, Masako; Hargitai, Joseph; Calder, R Brent; Greally, John M

    2012-01-01

    Massively-parallel sequencing (MPS) technologies and their diverse applications in genomics and epigenomics research have yielded enormous new insights into the physiology and pathophysiology of the human genome. The biggest hurdle remains the magnitude and diversity of the datasets generated, compromising our ability to manage, organize, process and ultimately analyse data. The Wiki-based Automated Sequence Processor (WASP), developed at the Albert Einstein College of Medicine (hereafter Einstein), uniquely manages to tightly couple the sequencing platform, the sequencing assay, sample metadata and the automated workflows deployed on a heterogeneous high performance computing cluster infrastructure that yield sequenced, quality-controlled and 'mapped' sequence data, all within the one operating environment accessible by a web-based GUI interface. WASP at Einstein processes 4-6 TB of data per week and since its production cycle commenced it has processed ~ 1 PB of data overall and has revolutionized user interactivity with these new genomic technologies, who remain blissfully unaware of the data storage, management and most importantly processing services they request. The abstraction of such computational complexity for the user in effect makes WASP an ideal middleware solution, and an appropriate basis for the development of a grid-enabled resource - the Einstein Genome Gateway - as part of the Extreme Science and Engineering Discovery Environment (XSEDE) program. In this paper we discuss the existing WASP system, its proposed middleware role, and its planned interaction with XSEDE to form the Einstein Genome Gateway.

  16. Secure portal.

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Cynthia Lee

    2007-09-01

    There is a need in security systems to rapidly and accurately grant access of authorized personnel to a secure facility while denying access to unauthorized personnel. In many cases this role is filled by security personnel, which can be very costly. Systems that can perform this role autonomously without sacrificing accuracy or speed of throughput are very appealing. To address the issue of autonomous facility access through the use of technology, the idea of a ''secure portal'' is introduced. A secure portal is a defined zone where state-of-the-art technology can be implemented to grant secure area access or to allow special privileges for an individual. Biometric technologies are of interest because they are generally more difficult to defeat than technologies such as badge swipe and keypad entry. The biometric technologies selected for this concept were facial and gait recognition. They were chosen since they require less user cooperation than other biometrics such as fingerprint, iris, and hand geometry and because they have the most potential for flexibility in deployment. The secure portal concept could be implemented within the boundaries of an entry area to a facility. As a person is approaching a badge and/or PIN portal, face and gait information can be gathered and processed. The biometric information could be fused for verification against the information that is gathered from the badge. This paper discusses a facial recognition technology that was developed for the purposes of providing high verification probabilities with low false alarm rates, which would be required of an autonomous entry control system. In particular, a 3-D facial recognition approach using Fisher Linear Discriminant Analysis is described. Gait recognition technology, based on Hidden Markov Models has been explored, but those results are not included in this paper. Fusion approaches for combining the results of the biometrics would be the next step in realizing

  17. A Happy Partnership--Using an Information Portal To Integrate Information Literacy Skills into an Undergraduate Foundation Course.

    Science.gov (United States)

    Hiscock, Jane; Marriott, Philip

    2003-01-01

    Reports on a collaboration between academic teaching staff who coordinate an undergraduate foundation course in computers and society at the University of South Australia. Highlights include information literacy and lifelong learning; the combination of face-to-face and online instruction; links from the portal; student assessment; search…

  18. MaNIDA: Integration of marine expedition information, data and publications: Data Portal of German Marine Research

    Science.gov (United States)

    Koppe, Roland; Scientific MaNIDA-Team

    2013-04-01

    The Marine Network for Integrated Data Access (MaNIDA) aims to build a sustainable e-infrastructure to support discovery and re-use of marine data from distinct data providers in Germany (see related abstracts in session ESSI 1.2). In order to provide users integrated access and retrieval of expedition or cruise metadata, data, services and publications as well as relationships among the various objects, we are developing (web) applications based on state of the art technologies: the Data Portal of German Marine Research. Since the German network of distributed content providers have distinct objectives and mandates for storing digital objects (e.g. long-term data preservation, near real time data, publication repositories), we have to cope with heterogeneous metadata in terms of syntax and semantic, data types and formats as well as access solutions. We have defined a set of core metadata elements which are common to our content providers and therefore useful for discovery and building relationships among objects. Existing catalogues for various types of vocabularies are being used to assure the mapping to community-wide used terms. We distinguish between expedition metadata and continuously harvestable metadata objects from distinct data providers. • Existing expedition metadata from distinct sources is integrated and validated in order to create an expedition metadata catalogue which is used as authoritative source for expedition-related content. The web application allows browsing by e.g. research vessel and date, exploring expeditions and research gaps by tracklines and viewing expedition details (begin/end, ports, platforms, chief scientists, events, etc.). Also expedition-related objects from harvesting are dynamically associated with expedition information and presented to the user. Hence we will provide web services to detailed expedition information. • Other harvestable content is separated into four categories: archived data and data products, near

  19. 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/.

  20. 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Inna Dubchak

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

  3. An Integrative Computational Approach for Prioritization of Genomic Variants

    Science.gov (United States)

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

    2014-01-01

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

  4. Integrative Genomics with Mediation Analysis in a Survival Context

    Directory of Open Access Journals (Sweden)

    Szilárd Nemes

    2013-01-01

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

  5. 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

  6. 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.

  7. Synteny Portal: a web-based application portal for synteny block analysis.

    Science.gov (United States)

    Lee, Jongin; Hong, Woon-Young; Cho, Minah; Sim, Mikang; Lee, Daehwan; Ko, Younhee; Kim, Jaebum

    2016-07-01

    Recent advances in next-generation sequencing technologies and genome assembly algorithms have enabled the accumulation of a huge volume of genome sequences from various species. This has provided new opportunities for large-scale comparative genomics studies. Identifying and utilizing synteny blocks, which are genomic regions conserved among multiple species, is key to understanding genomic architecture and the evolutionary history of genomes. However, the construction and visualization of such synteny blocks from multiple species are very challenging, especially for biologists with a lack of computational skills. Here, we present Synteny Portal, a versatile web-based application portal for constructing, visualizing and browsing synteny blocks. With Synteny Portal, users can easily (i) construct synteny blocks among multiple species by using prebuilt alignments in the UCSC genome browser database, (ii) visualize and download syntenic relationships as high-quality images, (iii) browse synteny blocks with genetic information and (iv) download the details of synteny blocks to be used as input for downstream synteny-based analyses, all in an intuitive and easy-to-use web-based interface. We believe that Synteny Portal will serve as a highly valuable tool that will enable biologists to easily perform comparative genomics studies by compensating limitations of existing tools. Synteny Portal is freely available at http://bioinfo.konkuk.ac.kr/synteny_portal.

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

    Science.gov (United States)

    Zhang, Xinyue; Huang, Jing

    2010-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Yi Ren

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

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

    Science.gov (United States)

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

    2017-04-05

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

  11. Database Description - PGDBj Registered plant list, Marker list, QTL list, Plant DB link & Genome analysis methods | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available d and funding Name: Database Integration Coordination Program (FY2011-FY2013) Integration of plant databases...ency (JST) Reference(s) Article title: Plant Genome DataBase Japan (PGDBj): A Portal Website for the Integ...ration of Plant Genome-Related Databases Author name(s): Erika Asamizu, Hisako Ichi

  12. 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.

  13. Implementing BEA Portal 92

    CERN Document Server

    Kolb, Mark

    2007-01-01

    Portals have come into their own in the last several years. Over this time, I have seen portal technology become the latest expression of businesses trying to organize the torrent of information that computers bring. BEA portal is a leader in portal technology. It allows for an enterprise level of support, stability, and capability. Portal 92 has the tools to make your next portal project a success. It also has the sophistication to keep your portal running and remaining relevant to your business. If you are investigating BEA Portal technology, or if you are a seasoned BEA administrator, you

  14. Wiki portals

    OpenAIRE

    Kočar, Anja

    2013-01-01

    In our everyday life we are faced with the internet and various web pages that are created on a particular topic. Construction of these can be addressed in different ways. One of them is the usage of wiki portals. Wiki is a collection of web pages, whose content is simple to create and modify, we only need a web browser and an internet connection. If we want to start our own wiki, we need a software called wiki engine. In this thesis we treat wiki as a system of websites, which enables ...

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-08-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2017-01-24

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

  19. 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).

  20. 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).

  1. 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...

  2. Noncirrotisk intrahepatisk portal hypertension

    DEFF Research Database (Denmark)

    Dam Fialla, Annette; Havelund, Troels

    2007-01-01

    Non-cirrhotic intrahepatic portal hypertension is characterized by portal hypertension in the absence of liver cirrhosis or portal vein thrombosis. The disease is common in the East and rarely seen in the West. Two cases with oesophageal varices are described. The histopathology is heterogeneous...... but includes vascular lesions and portal fibrosis. Patient management follows the current recommendations for variceal bleeding....

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

    Directory of Open Access Journals (Sweden)

    Bodour Salhia

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  7. Integrating the UPV Institutional Repository (RiuNet - DSpace) in the Courseware Management System (PoliformaT - Sakai) via the Digital Library Portal (PoliBuscador - MetaLib)

    OpenAIRE

    Ribes-Llopes, Inmaculada; Torres-Peris, Maria-Josep; García-Pau, Víctor

    2008-01-01

    This presentation deals on process of integration of the Universidad Politécnica de Valencia (UPV) institutional repository in the e-contents scenario. RiuNet, the institutional repository, has been developed in DSpace (manakin). It has been integrated in the Metalib portal called PoliBuscador. Thanks to this configuration RiuNet can be searchable from PoliformaT, the Courseware Management System of the UPV developed in Sakai. This communication presents problems, decisions and steps taken by...

  8. 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 .

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

    Science.gov (United States)

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

    2012-12-01

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

  10. The Knowledge Portal

    Data.gov (United States)

    Office of Personnel Management — Information on various courses, as well as personal data of employees and training records from The Knowledge Portal (TKP), a web-based training portal used for the...

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

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

    2011-03-14

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

  13. 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.

  14. Portals people, processes, technology

    CERN Document Server

    Cox, Andrew

    2006-01-01

    First applied to internet gateways such as Yahoo, the concept of the ""portal"" has evolved in a number of directions. How can information services best take advantage of internet portals to improve access to resources? This collection seeks answers to such questions, providing an overview of how portals are being used.

  15. Evaluating Open Source Portals

    Science.gov (United States)

    Goh, Dion; Luyt, Brendan; Chua, Alton; Yee, See-Yong; Poh, Kia-Ngoh; Ng, How-Yeu

    2008-01-01

    Portals have become indispensable for organizations of all types trying to establish themselves on the Web. Unfortunately, there have only been a few evaluative studies of portal software and even fewer of open source portal software. This study aims to add to the available literature in this important area by proposing and testing a checklist for…

  16. Noncirrotisk intrahepatisk portal hypertension

    DEFF Research Database (Denmark)

    Dam Fialla, Annette; Havelund, Troels

    2007-01-01

    Non-cirrhotic intrahepatic portal hypertension is characterized by portal hypertension in the absence of liver cirrhosis or portal vein thrombosis. The disease is common in the East and rarely seen in the West. Two cases with oesophageal varices are described. The histopathology is heterogeneous...

  17. Usability of Discovery Portals

    NARCIS (Netherlands)

    Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

    2013-01-01

    As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals

  18. Usability of Discovery Portals

    NARCIS (Netherlands)

    Bulens, J.D.; Vullings, L.A.E.; Houtkamp, J.M.; Vanmeulebrouk, B.

    2013-01-01

    As INSPIRE progresses to be implemented in the EU, many new discovery portals are built to facilitate finding spatial data. Currently the structure of the discovery portals is determined by the way spatial data experts like to work. However, we argue that the main target group for discovery portals

  19. 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.

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

    Science.gov (United States)

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

    2015-06-19

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2009-06-01

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

  3. 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.

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

    DEFF Research Database (Denmark)

    Han, Wenyuan; Feng, Xu; She, Qunxin

    2017-01-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    MacAulay Calum

    2008-10-01

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

  7. Portal hypertensiv gastropati

    DEFF Research Database (Denmark)

    Brinch, K; Møller, S; Henriksen, Jens Henrik Sahl

    1995-01-01

    Portal hypertensive gastropathy (PHG) as defined by congestive changes in the gastric mucosa owing to increased portal pressure, was first described about ten years ago. Whereas definition and grading of severity are still under debate, there is general agreement that PHG is a new clinical entity....... PHG is present in 50-80% of patients with liver cirrhosis. PHG is a major cause of upper gastrointestinal bleeding in patients with portal hypertension (25-90% depending on severity). Presence of portal hypertension is a prerequisite for the development of PHG, and reduction of portal pressure...

  8. Mobile Portal Implementation Strategy

    DEFF Research Database (Denmark)

    Gao, Ping; Damsgaard, Jan

    2005-01-01

    Mobile portal plays an important role in mobile commerce market. Current literature focuses on static analysis on the value chain of mobile portals. This article provides a dynamic perspective on mobile portal strategy. Drawing upon network economics, we describe mobile portal implementation...... as a fourphase process. In different phase, a portal provider has various challenges to overcome and adopt diverse strategies, and correspondingly the regulator has different foci. The conceptual framework proposed in this article offers a basis for further analyses on the market dynamics of mobile commerce......, and can be generalized to studying other networked technologies...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    Chen, Xi; Wang, Lily; Ishwaran, Hemant

    2010-09-01

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

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

    DEFF Research Database (Denmark)

    Zhao, Wenming; Wang, Jing; He, Ximiao

    2004-01-01

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

  12. viruSITE—integrated database for viral genomics

    Science.gov (United States)

    Stano, Matej; Beke, Gabor; Klucar, Lubos

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Dark Axion Portal

    CERN Document Server

    Kaneta, Kunio; Yun, Seokhoon

    2016-01-01

    The dark photon and the axion (or axion-like particle) are among the popular light particles of the hidden sector. Each of them has been actively searched for through the couplings called the vector portal and the axion portal. We introduce a new portal connecting the dark photon and the axion (axion--photon--dark photon, axion--dark photon--dark photon), which emerges in the presence of the two particles. This dark axion portal is genuinely new couplings, not just from a product of the vector portal and the axion portal, because of the internal structure of these couplings. We present a simple model that realizes the dark axion portal and discuss why it warrants rich phenomenology.

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

    OpenAIRE

    Nina Ratna Djuita; Rita Megia

    2010-01-01

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

  16. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    NEALSON, KENNETH H.

    2013-10-15

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

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

    Institute of Scientific and Technical Information of China (English)

    Yuan Wei; Fang Xu; Peining Li

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-25

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

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

    Science.gov (United States)

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

    2017-03-01

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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Intikhab Alam

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

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

    Directory of Open Access Journals (Sweden)

    Mathias Kuhring

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

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

    Science.gov (United States)

    2012-09-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  5. 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

  6. 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 ...

  7. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-08

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

  8. Dark Axion Portal

    OpenAIRE

    Kaneta, Kunio; Lee, Hye-Sung(Theory Division, CERN, CH-1211, Geneva 23, Switzerland); Yun, Seokhoon

    2016-01-01

    The dark photon and the axion (or axion-like particle) are among the popular light particles of the hidden sector. Each of them has been actively searched for through the couplings called the vector portal and the axion portal. We introduce a new portal connecting the dark photon and the axion (axion-photon-dark photon, axion-dark photon-dark photon), which emerges in the presence of the two particles. This dark axion portal is genuinely new couplings, not just from a product of the vector po...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mazzuchelli Juliana

    2012-09-01

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

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

    Science.gov (United States)

    Krishnan, Vaidehi; Ito, Yoshiaki

    2017-01-01

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

  12. Integrated genomic analysis of survival outliers in glioblastoma.

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2001-12-01

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

  14. 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.

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

    Science.gov (United States)

    McKinnon, Peter J

    2017-06-15

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

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

    Science.gov (United States)

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

    2011-12-31

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

  17. 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

  18. Genome maintenance and transcription integrity in ageing and disease

    Directory of Open Access Journals (Sweden)

    Stefanie eWolters

    2013-02-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  20. 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.

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

    Science.gov (United States)

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

    2016-05-13

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

  2. 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

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

    OpenAIRE

    2013-01-01

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

  4. Portal cholangiopathy: case report

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Almeida Maia

    2014-01-01

    Full Text Available The present report describes the case of a child that after blunt abdominal trauma presented with portal thrombosis followed by progressive splenomegaly and jaundice. Ultrasonography and percutaneous cholangiography revealed biliary dilatation secondary to choledochal stenosis caused by dilated peribiliary veins, characterizing a case of portal biliopathy. The present case report is aimed at presenting an uncommon cause of this condition.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  8. Portal Vein Thrombosis

    Directory of Open Access Journals (Sweden)

    Ronny Cohen

    2015-01-01

    Full Text Available Portal vein thrombosis (PVT is the blockage or narrowing of the portal vein by a thrombus. It is relatively rare and has been linked with the presence of an underlying liver disease or prothrombotic disorders. We present a case of a young male who presented with vague abdominal symptoms for approximately one week. Imaging revealed the presence of multiple nonocclusive thrombi involving the right portal vein, the splenic vein, and the left renal vein, as well as complete occlusion of the left portal vein and the superior mesenteric vein. We discuss pathogenesis, clinical presentation, and management of both acute and chronic thrombosis. The presence of PVT should be considered as a clue for prothrombotic disorders, liver disease, and other local and general factors that must be carefully investigated. It is hoped that this case report will help increase awareness of the complexity associated with portal vein thrombosis among the medical community.

  9. The XCAT Science Portal

    Directory of Open Access Journals (Sweden)

    Sriram Krishnan

    2002-01-01

    Full Text Available This paper describes the design and prototype implementation of the XCAT Grid Science Portal. The portal lets grid application programmers script complex distributed computations and package these applications with simple interfaces for others to use. Each application is packaged as a notebook which consists of web pages and editable parameterized scripts. The portal is a workstation-based specialized personal web server, capable of executing the application scripts and launching remote grid applications for the user. The portal server can receive event streams published by the application and grid resource information published by Network Weather Service (NWS [35] or Autopilot [16] sensors. Notebooks can be published and stored in web based archives for others to retrieve and modify. The XCAT Grid Science Portal has been tested with various applications, including the distributed simulation of chemical processes in semiconductor manufacturing and collaboratory support for X-ray crystallographers.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Roadside Tracker Portal-less Portal Monitor

    Energy Technology Data Exchange (ETDEWEB)

    Ziock, Klaus-Peter [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cheriyadat, Anil M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bradley, Eric Craig [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cunningham, Mark F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fabris, Lorenzo [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Goddard, Jr, James Samuel [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hornback, Donald Eric [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Karnowski, Thomas Paul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kerekes, Ryan A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Newby, Jason [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2013-07-01

    This report documents the full development cycle of the Roadside Tracker (RST) Portal-less Portal monitor (Fig. 1) funded by DHS DNDO. The project started with development of a proof-of-feasibility proto-type, proceeded through design and construction of a proof-of-concept (POC) prototype, a test-and-evaluation phase, participation in a Limited Use Exercise that included the Standoff Radiation Detections Systems developed under an Advanced Technology Demonstration and concluded with participation in a Characterization Study conducted by DNDO.

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

    Science.gov (United States)

    Moreno-Moral, Aida

    2016-01-01

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

  13. Fluorescent reporters for markerless genomic integration in Staphylococcus aureus

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peterson Elena S

    2012-04-01

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

  15. Effect of Fluid Shear Stress on Portal Vein Remodeling in a Rat Model of Portal Hypertension

    Directory of Open Access Journals (Sweden)

    Bin Wen

    2015-01-01

    Full Text Available Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO, synthase (NOS, and endothelin-1 (ET-1 of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P<0.05 versus baseline. The fluid shear stress declined from week 4 onwards (P<0.01 versus control group. NO, NOS, and ET-1 increased after repeated CCI4 injections. Hematoxylin and eosin staining showed thickened portal vein walls, with increased inside and outside diameters. Electron microscopy revealed different degrees of endothelial cell degeneration, destruction of basement membrane integrity, proliferating, and hypertrophic smooth muscle cells. Conclusions. Fluid shear stress not only influenced the biomechanical environment of the portal vein but also participated in vascular remodeling.

  16. 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

  17. An Approach for harmonizing European Water Portals

    Science.gov (United States)

    Pesquer, Lluís; Stasch, Christoph; Masó, Joan; Jirka, Simon; Domingo, Xavier; Guitart, Francesc; Turner, Thomas; Hinderk Jürrens, Eike

    2017-04-01

    A number of European funded research projects is developing novel solutions for water monitoring, modeling and management. To generate innovations in the water sector, third parties from industry and the public sector need to take up the solutions and bring them into the market. A variety of portals exists to support this move into the market. Examples on the European level are the EIP Water Online Marketplace(1), the WaterInnEU Marketplace(2), the WISE RTD Water knowledge portal(3), the WIDEST- ICT for Water Observatory(4) or the SWITCH-ON Virtual Product Market and Virtual Water-Science Laboratory(5). Further innovation portals and initiatives exist on the national or regional level, for example, the Denmark knows water platform6 or the Dutch water alliance(7). However, the different portals often cover the same projects, the same products and the same services. Since they are technically separated and have their own data models and databases, people need to duplicate information and maintain it at several endpoints. This requires additional efforts and hinders the interoperable exchange between these portals and tools using the underlying data. In this work, we provide an overview on the existing portals and present an approach for harmonizing and integrating common information that is provided across different portals. The approach aims to integrate the common in formation in a common database utilizing existing vocabularies, where possible. An Application Programming Interface allows access the information in a machine-readable way and utilizing the information in other applications beyond description and discovery purposes. (1) http://www.eip-water.eu/my-market-place (2) https://marketplace.waterinneu.org (3) http://www.wise-rtd.info/ (4) http://iwo.widest.eu (5) http://www.switch-on-vwsl.eu/ (6) http://www.rethinkwater.dk/ (7) http://wateralliance.nl/

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

    Directory of Open Access Journals (Sweden)

    Ng Raymond T

    2008-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhi; CUI; Zhizhong

    2005-01-01

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

  20. Congenital preduodenal portal vein

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Jin; Hwang, Mi Soo; Huh, Young Soo; Park, Bok Hwan [College of Medicine, Youngnam University, Gyeongsan (Korea, Republic of)

    1991-03-15

    Congenital preduodenal portal vein, first reported by Knight in 1921, is an extremely rare congenital anomaly in which the portal vein passes anteriorly to the duodenum rather than posteriorly in its normal location. It is of surgical significance because it may cause difficulties in operations involving the gall bladder, biliary duct, or duodenum. Recently, we experienced 2 cases of preduodenal portal vein. One was found during surgical exploration for the diagnosis and correction of malrotation of the bowels and the other in a 3 day-old male newborn associated with dextrocardia, situs inversus, and duodenal obstruction by diaphragm. We report these 2 cases with a review of the literature.

  1. Earthdata Developer Portal poster

    Science.gov (United States)

    Plofchan, P.

    2016-12-01

    A common theme at community conferences in the Earth science domain is the need for more integration with related services, clearer documentation for services available, and a general simplification of what it takes to leverage existing tools so that setup and administration time can be minimized and time spent researching can be maximized. NASA's Earthdata Developer Portal (EDP) is the newly-created central location for documentation related to interacting with services offered by the EOSDIS community. The EDP will provide technical documentation for APIs, process documentation that provides real-world examples of how to use existing APIs in the real world, release notes for applications and services so that the entire community can stay up to date on recent updates, and best practice suggestions to improve implementation of both front-end and back-end services. Application and service owners will own their documentation while the EDP will ingest the documentation, serve it up in an interface using both industry standard tools, such as Swagger, and custom "adapters". The content is then styled to ensure consistency with other documentation found throughout the site and will be made searchable from a single location. "Getting Started" paths will also provide those users new to the space a simple path to follow to perform common tasks such as "searching and getting data" or "hosting an application on the Earthdata platform."

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

    Directory of Open Access Journals (Sweden)

    Barbara Felice

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

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

    Directory of Open Access Journals (Sweden)

    Martín Yusé

    2011-12-01

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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Xiaojun Xia

    2013-12-01

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

  7. 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.

  8. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

  11. Dissecting the brown adipogenic regulatory network using integrative genomics

    Science.gov (United States)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Képès François

    2010-04-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hao eLuo

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Vladimir A Belyi

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

  19. Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

    Institute of Scientific and Technical Information of China (English)

    Francisco Eizayaga; Camila Scorticati; Juan P Prestifilippo; Salvador Romay; Maria A Fernandez; José L Castro; Abraham Lemberg; Juan C Perazzo

    2006-01-01

    AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized.METHODS: Adult male Wistar rats were divided into four groups: Group Ⅰ: Sham14d, sham operated; Group Ⅱ: PH14d, portal vein stenosis; (both groups were used 14 days after surgery); Group Ⅲ: Sham40d, Sham operated and Group Ⅳ: PH40d Portal vein stenosis (Groups Ⅱ and Ⅳ used 40 d after surgery). Plasma ammonia,plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded.RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high,and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished.When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished.CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Orlov Y.L.

    2012-08-01

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

  2. Liferay Portal Systems Development

    CERN Document Server

    Yuan, Jonas X

    2012-01-01

    This book focuses on teaching by example. Every chapter provides an overview, and then dives right into hands-on examples so you can see and play with the solution in your own environment. This book is for Java developers who don't need any prior experience with Liferay portal. Although Liferay portal makes heavy use of open source frameworks, no prior experience of using these is assumed.

  3. ELECTRONIC COMMERCE PORTAL

    OpenAIRE

    Georgeta Soava

    2011-01-01

    Today companies are faced with the need to exploit technology changing computer environments, in order to improve customer satisfaction and reduce costs. A successful approach to electronic portals is an effective demonstration of the new ways of relating to the client. The objectives that we have considered for the realization of e-commerce portal can be summarized as follows: structured communication, effective collaboration, complet and closed circuit of orders and deliveries, inventory op...

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

    Directory of Open Access Journals (Sweden)

    Xuewen Wang

    2016-09-01

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

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

    Science.gov (United States)

    Wang, Xuewen; Wang, Le

    2016-01-01

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

  6. 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

  7. 基于微信公众号建立湖南烟草一体化移动应用门户的探析%Based on WeChat public, Hunan Tobacco Integration of Mobile Application Portal Analysis

    Institute of Scientific and Technical Information of China (English)

    申玉华; 唐绅

    2015-01-01

    该文针对微信公众号的类别和湖南烟草业务应用内容进行了分析,提出了在湖南烟草应用微信公众号建设一体化移动应用门户的构想,并论述了建设微信公众平台的总体设计思路与设计架构,对建设微信公众平台的实施风险进行了分析,指出了建设湖南烟草一体化移动应用门户平台的重要意义.%Public based on WeChat, categories and Hunan tobacco business application contents are analyzed and present?ed in Hunan tobacco use WeChat public Numbers on the idea of the mobile application portal construction integration, and discusses the construction of WeChat public platform of the overall architecture, design idea and design for the im?plementation of the WeChat public platform construction risks are analyzed, points out the construction of the impor?tance of integration of Hunan tobacco mobile application portal platform.

  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. 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.

  10. 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.

  11. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. 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.

  14. Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium

    Directory of Open Access Journals (Sweden)

    Nathan Salomonis

    2016-07-01

    Full Text Available The rigorous characterization of distinct induced pluripotent stem cells (iPSC derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community.

  15. Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.

    Science.gov (United States)

    Salomonis, Nathan; Dexheimer, Phillip J; Omberg, Larsson; Schroll, Robin; Bush, Stacy; Huo, Jeffrey; Schriml, Lynn; Ho Sui, Shannan; Keddache, Mehdi; Mayhew, Christopher; Shanmukhappa, Shiva Kumar; Wells, James; Daily, Kenneth; Hubler, Shane; Wang, Yuliang; Zambidis, Elias; Margolin, Adam; Hide, Winston; Hatzopoulos, Antonis K; Malik, Punam; Cancelas, Jose A; Aronow, Bruce J; Lutzko, Carolyn

    2016-07-12

    The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. R2 Water Quality Portal Monitoring Stations

    Science.gov (United States)

    The Water Quality Data Portal (WQP) provides an easy way to access data stored in various large water quality databases. The WQP provides various input parameters on the form including location, site, sampling, and date parameters to filter and customize the returned results. The The Water Quality Portal (WQP) is a cooperative service sponsored by the United States Geological Survey (USGS), the Environmental Protection Agency (EPA) and the National Water Quality Monitoring Council (NWQMC) that integrates publicly available water quality data from the USGS National Water Information System (NWIS) the EPA STOrage and RETrieval (STORET) Data Warehouse, and the USDA ARS Sustaining The Earth??s Watersheds - Agricultural Research Database System (STEWARDS).

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

    Science.gov (United States)

    Masseroli, Marco; Canakoglu, Arif; Ceri, Stefano

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-04

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

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

    Science.gov (United States)

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

    2004-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  3. Portal venous stent placement for treatment of portal hypertension caused by benign main portal vein stenosis

    Institute of Scientific and Technical Information of China (English)

    Hong Shan; Xiang-Sheng Xiao; Ming-Sheng Huang; Qiang Ouyang; Zai-Bo Jiang

    2005-01-01

    AIM: To evaluate the value of endovascular stent in the treatment of portal hypertension caused by benign main portal vein stenosis.METHODS: Portal vein stents were implanted in six patients with benign main portal vein stenosis (inflammatory stenosis in three cases, postprocedure of liver transplantation in another three cases). Changes in portal vein pressure, portal vein patency, relative clinical symptoms, complications, and survival were evaluated.RESULTS: Six metallic stents were successfully placed across the portal vein stenotic or obstructive lesions in six patients. Mean portal venous pressure decreased significantly after stent implantation from (37.3±4.7) cm H2O to (18.0±1.9) cm H2O. The portal blood flow restoredand the symptoms caused by portal hypertension were eliminated. There were no severe procedure-related complications. The patients were followed up for 1-48 mo. The portal vein remained patent during follow-up. All patients survived except for one patient who died of other complications of liver transplantation. CONCLUSION: Percutaneous portal vein stent placement for the treatment of portal hypertension caused by benign main portal vein stenosis is safe and effective.

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

    Directory of Open Access Journals (Sweden)

    Giandomenico Turchiano

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

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

    Science.gov (United States)

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

    2014-01-01

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

  6. The BioMart community portal: An innovative alternative to large, centralized data repositories

    OpenAIRE

    Smedley, Damian; Haider, Syed; Durinck, Steffen; Pandini, Luca; Provero, Paolo; Allen, James; Arnaiz, Olivier; Awedh, Mohammad Hamza; Baldock, Richard; Barbiera, Giulia; Bardou, Philippe; Beck, Tim; Blake, Andrew; Bonierbale, Merideth; Brookes, Anthony J

    2015-01-01

    The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by thei...

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

    Directory of Open Access Journals (Sweden)

    Kennedy Breandan

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2006-11-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nur Zarina Ali Hassan

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

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

    DEFF Research Database (Denmark)

    Suravajhala, Prashanth; Kogelman, Lisette; Kadarmideen, Haja

    2016-01-01

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

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

    Science.gov (United States)

    Kaufer, Benedikt B

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  14. 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.

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

    Science.gov (United States)

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

    2008-11-01

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

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

    Science.gov (United States)

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

    2016-10-14

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-07-31

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

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

    DEFF Research Database (Denmark)

    Liu, Guodong; Marras, Antonio; Nielsen, Jens

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    van Wieringen Wessel N

    2012-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohit Verma

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

  6. Designing the Search Service for Enterprise Portal based on Oracle Universal Content Management

    Science.gov (United States)

    Bauer, K. S.; Kuznetsov, D. Y.; Pominov, A. D.

    2017-01-01

    Enterprise Portal is an important part of an organization in informative and innovative space. The portal provides collaboration between employees and the organization. This article gives a valuable background of Enterprise Portal and technologies. The paper presents Oracle WebCenter Portal and UCM Server integration in detail. The focus is on tools for Enterprise Portal and on Search Service in particular. The paper also presents several UML diagrams to describe the use of cases for Search Service and main components of this application.

  7. The EBI enzyme portal.

    Science.gov (United States)

    Alcántara, Rafael; Onwubiko, Joseph; Cao, Hong; Matos, Paula de; Cham, Jennifer A; Jacobsen, Jules; Holliday, Gemma L; Fischer, Julia D; Rahman, Syed Asad; Jassal, Bijay; Goujon, Mikael; Rowland, Francis; Velankar, Sameer; López, Rodrigo; Overington, John P; Kleywegt, Gerard J; Hermjakob, Henning; O'Donovan, Claire; Martín, María Jesús; Thornton, Janet M; Steinbeck, Christoph

    2013-01-01

    The availability of comprehensive information about enzymes plays an important role in answering questions relevant to interdisciplinary fields such as biochemistry, enzymology, biofuels, bioengineering and drug discovery. At the EMBL European Bioinformatics Institute, we have developed an enzyme portal (http://www.ebi.ac.uk/enzymeportal) to provide this wealth of information on enzymes from multiple in-house resources addressing particular data classes: protein sequence and structure, reactions, pathways and small molecules. The fact that these data reside in separate databases makes information discovery cumbersome. The main goal of the portal is to simplify this process for end users.

  8. Personalization Methods for Internet Portals

    Directory of Open Access Journals (Sweden)

    Barbara Dębska

    2012-06-01

    Full Text Available The article presents methods of acquiring and gathering data about users of internet portals, with particular emphasis on educational portals. Definitions, aims and tasks related to the process of personalization of e-learning portals are thoroughly discussed. So are knowledge acquisition techniques applied in personalization, especially artificial intelligence methods.

  9. Ten Keys to the Portal

    Science.gov (United States)

    Schaffhauser, Dian

    2011-01-01

    Successful web portals help users stay informed, in touch, and up to speed. They are also a telling window into the efficiency of one's institution. To develop a cutting-edge portal takes planning, communication, and research. In this article, the author presents and discusses 10 keys to portal success: (1) make critical info visible; (2) make the…

  10. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Directory of Open Access Journals (Sweden)

    Hongbao Cao

    Full Text Available Various types of genomic data (e.g., SNPs and mRNA transcripts have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls and expression data for 22283 genes in 80 subjects (40 cases and 40 controls to identify significant genes for osteoporosis (OP. Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'. Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc. that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  11. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Science.gov (United States)

    Cao, Hongbao; Lei, Shufeng; Deng, Hong-Wen; Wang, Yu-Ping

    2012-01-01

    Various types of genomic data (e.g., SNPs and mRNA transcripts) have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions) that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC) method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls) and expression data for 22283 genes in 80 subjects (40 cases and 40 controls) to identify significant genes for osteoporosis (OP). Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'). Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc.) that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  12. Construction of an ortholog database using the semantic web technology for integrative analysis of genomic data.

    Science.gov (United States)

    Chiba, Hirokazu; Nishide, Hiroyo; Uchiyama, Ikuo

    2015-01-01

    Recently, various types of biological data, including genomic sequences, have been rapidly accumulating. To discover biological knowledge from such growing heterogeneous data, a flexible framework for data integration is necessary. Ortholog information is a central resource for interlinking corresponding genes among different organisms, and the Semantic Web provides a key technology for the flexible integration of heterogeneous data. We have constructed an ortholog database using the Semantic Web technology, aiming at the integration of numerous genomic data and various types of biological information. To formalize the structure of the ortholog information in the Semantic Web, we have constructed the Ortholog Ontology (OrthO). While the OrthO is a compact ontology for general use, it is designed to be extended to the description of database-specific concepts. On the basis of OrthO, we described the ortholog information from our Microbial Genome Database for Comparative Analysis (MBGD) in the form of Resource Description Framework (RDF) and made it available through the SPARQL endpoint, which accepts arbitrary queries specified by users. In this framework based on the OrthO, the biological data of different organisms can be integrated using the ortholog information as a hub. Besides, the ortholog information from different data sources can be compared with each other using the OrthO as a shared ontology. Here we show some examples demonstrating that the ortholog information described in RDF can be used to link various biological data such as taxonomy information and Gene Ontology. Thus, the ortholog database using the Semantic Web technology can contribute to biological knowledge discovery through integrative data analysis.

  13. Integrated physical, genetic and genome map of chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Varshney, Rajeev K; Mir, Reyazul Rouf; Bhatia, Sabhyata; Thudi, Mahendar; Hu, Yuqin; Azam, Sarwar; Zhang, Yong; Jaganathan, Deepa; You, Frank M; Gao, Jinliang; Riera-Lizarazu, Oscar; Luo, Ming-Cheng

    2014-03-01

    Physical map of chickpea was developed for the reference chickpea genotype (ICC 4958) using bacterial artificial chromosome (BAC) libraries targeting 71,094 clones (~12× coverage). High information content fingerprinting (HICF) of these clones gave high-quality fingerprinting data for 67,483 clones, and 1,174 contigs comprising 46,112 clones and 3,256 singletons were defined. In brief, 574 Mb genome size was assembled in 1,174 contigs with an average of 0.49 Mb per contig and 3,256 singletons represent 407 Mb genome. The physical map was linked with two genetic maps with the help of 245 BAC-end sequence (BES)-derived simple sequence repeat (SSR) markers. This allowed locating some of the BACs in the vicinity of some important quantitative trait loci (QTLs) for drought tolerance and reistance to Fusarium wilt and Ascochyta blight. In addition, fingerprinted contig (FPC) assembly was also integrated with the draft genome sequence of chickpea. As a result, ~965 BACs including 163 minimum tilling path (MTP) clones could be mapped on eight pseudo-molecules of chickpea forming 491 hypothetical contigs representing 54,013,992 bp (~54 Mb) of the draft genome. Comprehensive analysis of markers in abiotic and biotic stress tolerance QTL regions led to identification of 654, 306 and 23 genes in drought tolerance "QTL-hotspot" region, Ascochyta blight resistance QTL region and Fusarium wilt resistance QTL region, respectively. Integrated physical, genetic and genome map should provide a foundation for cloning and isolation of QTLs/genes for molecular dissection of traits as well as markers for molecular breeding for chickpea improvement.

  14. A Profile of Native Integration Sites Used by φC31 Integrase in the Bovine Genome

    Institute of Scientific and Technical Information of China (English)

    Lijuan Qu; Qingwen Ma; Zaiwei Zhou; Haiyan Ma; Ying Huang; Shuzhen Huang; Fanyi Zeng; Yitao Zeng

    2012-01-01

    The Streptomyces phage φC31 integrase can efficiently target attB-beadng transgenes to endogenous pseudo attP sites within mammalian genomes.To better understand the activity of φC31 integrase in the bovine genome,DNA sequences of 44 integration events were analyzed,and 32 pseudo attP sites were identified.The majority of these sites share a sequence motif that contains inverted repeats and has similarities to wild-type attP site.Genomic DNA flanking these sites typically contained repetitive sequence elements,such as short and long interspersed repetitive elements.These sequence features indicate that DNA sequence recognition plays an important role in guiding φC31-mediated site-specific integration.In addition,BF27 integration hotspot sites were identified in the bovine genome,which accounted for 13.6% of all isolated integration events and mapped to an intron of the deleted in liver cancer 1 (DLC1) gene.Also we found that the pseudo attP sites in the bovine genome had other features in common with those in the human genome.This study represents the first time that the sequence features of pseudo attP sites in the bovine genome were analyzed.We conclude that this sitespecific integrase system has great potential for applied modifications of the bovine genome.

  15. Integrated Database And Knowledge Base For Genomic Prospective Cohort Study In Tohoku Medical Megabank Toward Personalized Prevention And Medicine.

    Science.gov (United States)

    Ogishima, Soichi; Takai, Takako; Shimokawa, Kazuro; Nagaie, Satoshi; Tanaka, Hiroshi; Nakaya, Jun

    2015-01-01

    The Tohoku Medical Megabank project is a national project to revitalization of the disaster area in the Tohoku region by the Great East Japan Earthquake, and have conducted large-scale prospective genome-cohort study. Along with prospective genome-cohort study, we have developed integrated database and knowledge base which will be key database for realizing personalized prevention and medicine.

  16. Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework.

    Science.gov (United States)

    Yang, Hai; Wei, Qiang; Zhong, Xue; Yang, Hushan; Li, Bingshan

    2017-02-15

    Comprehensive catalogue of genes that drive tumor initiation and progression in cancer is key to advancing diagnostics, therapeutics and treatment. Given the complexity of cancer, the catalogue is far from complete yet. Increasing evidence shows that driver genes exhibit consistent aberration patterns across multiple-omics in tumors. In this study, we aim to leverage complementary information encoded in each of the omics data to identify novel driver genes through an integrative framework. Specifically, we integrated mutations, gene expression, DNA copy numbers, DNA methylation and protein abundance, all available in The Cancer Genome Atlas (TCGA) and developed iDriver, a non-parametric Bayesian framework based on multivariate statistical modeling to identify driver genes in an unsupervised fashion. iDriver captures the inherent clusters of gene aberrations and constructs the background distribution that is used to assess and calibrate the confidence of driver genes identified through multi-dimensional genomic data. We applied the method to 4 cancer types in TCGA and identified candidate driver genes that are highly enriched with known drivers. (e.g.: P < 3.40 × 10 -36 for breast cancer). We are particularly interested in novel genes and observed multiple lines of supporting evidence. Using systematic evaluation from multiple independent aspects, we identified 45 candidate driver genes that were not previously known across these 4 cancer types. The finding has important implications that integrating additional genomic data with multivariate statistics can help identify cancer drivers and guide the next stage of cancer genomics research. The C ++ source code is freely available at https://medschool.vanderbilt.edu/cgg/ . hai.yang@vanderbilt.edu or bingshan.li@Vanderbilt.Edu. Supplementary data are available at Bioinformatics online.

  17. TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.

    Science.gov (United States)

    Cumbo, Fabio; Fiscon, Giulia; Ceri, Stefano; Masseroli, Marco; Weitschek, Emanuel

    2017-01-03

    Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments.

  18. 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

  19. 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.

  20. Earthdata Developer Portal

    Science.gov (United States)

    Plofchan, Peter; Reese, Mark; Siarto, Jeff; Clark, Nathan

    2016-01-01

    The Earthdata Developer Portal provides clear paths to get you started with core EOSDIS applications. Each path is accompanied by an overview page that explains the goal of the path and a short overview of each element along with links for detailed documentation of each component.

  1. UNESCO Archive Portal

    Directory of Open Access Journals (Sweden)

    2004-06-01

    Full Text Available A review to the web site of UNESCO Archive Portal which work as a directory for archive and documents web sites , also offer a news and events on archive , the review showing the categories of the site , it's services , and the classification of the web sites in the directories.

  2. Treatment of portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Khurram Bari; Guadalupe Garcia-Tsao

    2012-01-01

    Portal hypertension is the main complication of cirrhosis and is defined as an hepatic venous pressure gradient (HVPG) of more than 5 mmHg.Clinically significant portal hypertension is defined as HVPG of 10 mmHg or more.Development of gastroesophageal varices and variceal hemorrhage are the most direct consequence of portal hypertension.Over the last decades significant advancements in the field have led to standard treatment options.These clinical recommendations have evolved mostly as a result of randomized controlled trials and consensus conferences among experts where existing evidence has been reviewed and future goals for research and practice guidelines have been proposed.Management of varices/variceal hemorrhage is based on the clinical stage of portal hypertension.No specific treatment has shown to prevent the formation of varices.Prevention of first variceal hemorrhage depends on the size/characteristics of varices.In patients with small varices and high risk of bleeding,nonselective β-blockers are recommended,while patients with medium/large varices can be treated with either β-blockers or esophageal band ligation.Standard of care for acute variceal hemorrhage consists of vasoactive drugs,endoscopic band ligation and antibiotics prophylaxis.Transjugular intrahepatic portosystemic shunt (TIPS) is reserved for those who fail standard of care or for patients who are likely to fail ("early TIPS").Prevention of recurrent variceal hemorrhage consists of the combination of β-blockers and endoscopic band ligation.

  3. BRAZILIAN NEWS PORTALS CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Heloiza G. Herckovitz

    2011-02-01

    Full Text Available A content analysis of four Brazilian news media portals found that economic news dominated the top headlines with little attention paid to education, the environment and welfare. Other trends included a focus on local events and national news sources, reliance on few sources, mostly official ones, and a low percentage of news that fitted the concept of newsworthiness (a combination of both social significance and deviance concepts. Other findings of a study of 432 top news stories published by UOL, Estadão, iG and Terra during a 15-day period between February and March 2008 indicate that the top portions of the portals’ front pages carry news that lacks story depth, editorial branding, and multimedia applications. The results suggest that online news portals are in their infancy although Brazil has the largest online population of Latin America. This study hopes to shed light on the gatekeeping process in Brazilian news portals. Brazilian media portals have yet to become a significant editorial force able to provide knowledge about social issues and public affairs in a socially responsible fashione.

  4. Studies in portal hypertension

    NARCIS (Netherlands)

    H.R. van Buuren (Henk)

    2002-01-01

    textabstractOur work focussed on one of the most frequent and serious complications of portal hypertension i.e. variceal bleeding. In particular, studies were initiated aimed at developing a more effective therapeutic strategy for the primary and secondary prevention of variceal bleeding. Aspects of

  5. Messenger RNA- versus retrovirus-based induced pluripotent stem cell reprogramming strategies: analysis of genomic integrity.

    Science.gov (United States)

    Steichen, Clara; Luce, Eléanor; Maluenda, Jérôme; Tosca, Lucie; Moreno-Gimeno, Inmaculada; Desterke, Christophe; Dianat, Noushin; Goulinet-Mainot, Sylvie; Awan-Toor, Sarah; Burks, Deborah; Marie, Joëlle; Weber, Anne; Tachdjian, Gérard; Melki, Judith; Dubart-Kupperschmitt, Anne

    2014-06-01

    The use of synthetic messenger RNAs to generate human induced pluripotent stem cells (iPSCs) is particularly appealing for potential regenerative medicine applications, because it overcomes the common drawbacks of DNA-based or virus-based reprogramming strategies, including transgene integration in particular. We compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus-derived iPSCs generated in strictly comparable conditions, by single-nucleotide polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA-derived iPSCs do not differ significantly from the parental fibroblasts in SNP analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs seemed independent of the reprogramming method, instead appearing to be clone-dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs differentiated efficiently into hepatoblasts and that these cells did not load additional CNVs during differentiation. The integration-free hepatoblasts that were generated constitute a new tool for the study of diseased hepatocytes derived from patients' iPSCs and their use in the context of stem cell-derived hepatocyte transplantation. Our findings also highlight the need to conduct careful studies on genome integrity for the selection of iPSC lines before using them for further applications.

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

    Directory of Open Access Journals (Sweden)

    Juliana Gonçalves

    2016-01-01

    Full Text Available Chromosomal fragile sites (FSs are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs. The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data.

  7. [PIV: a computer-aided portal image verification system].

    Science.gov (United States)

    Fu, Weihua; Zhang, Hongzhi; Wu, Jing

    2002-12-01

    Portal image verification (PIV) is one of the key actions in QA procedure for sophisticated accurate radiotherapy. The purpose of this study was to develop a PIV software as a tool for improving the accuracy and visualization of portal field verification and computing field placement errors. PIV was developed in the visual C++ integrated environment under Windows 95 operating system. It can improve visualization by providing tools for image processing and multimode images display. Semi-automatic register methods make verification more accurate than view-box method. It can provide useful quantitative errors for regular fields. PIV is flexible and accurate. It is an effective tool for portal field verification.

  8. Portal Tools for Targeting Climate Information Users: The NIDIS Experience

    Science.gov (United States)

    Owen, T.; Brewer, M.

    2008-12-01

    Translation of scientific information for targeted user groups is a critical challenge facing the development of any comprehensive climate services framework. This talk explores the lessons learned from the development of a National Integrated Drought Information System (NIDIS) portal (drought.gov) to this end. The NIDIS portal focuses on communities of shared user interest, distinct tabular and map-based data accessibility pathways, and the judicious use of database crawlers to incorporate new and emerging data and information. These foci are informing the development of a climate services portal within NOAA scheduled for initial release in 2009.

  9. Fungal Genomics for Energy and Environment

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2013-03-11

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Sequencing Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 200 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  10. 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.

  11. ZikaVR: An Integrated Zika Virus Resource for Genomics, Proteomics, Phylogenetic and Therapeutic Analysis

    Science.gov (United States)

    Gupta, Amit Kumar; Kaur, Karambir; Rajput, Akanksha; Dhanda, Sandeep Kumar; Sehgal, Manika; Khan, Md. Shoaib; Monga, Isha; Dar, Showkat Ahmad; Singh, Sandeep; Nagpal, Gandharva; Usmani, Salman Sadullah; Thakur, Anamika; Kaur, Gazaldeep; Sharma, Shivangi; Bhardwaj, Aman; Qureshi, Abid; Raghava, Gajendra Pal Singh; Kumar, Manoj

    2016-01-01

    Current Zika virus (ZIKV) outbreaks that spread in several areas of Africa, Southeast Asia, and in pacific islands is declared as a global health emergency by World Health Organization (WHO). It causes Zika fever and illness ranging from severe autoimmune to neurological complications in humans. To facilitate research on this virus, we have developed an integrative multi-omics platform; ZikaVR (http://bioinfo.imtech.res.in/manojk/zikavr/), dedicated to the ZIKV genomic, proteomic and therapeutic knowledge. It comprises of whole genome sequences, their respective functional information regarding proteins, genes, and structural content. Additionally, it also delivers sophisticated analysis such as whole-genome alignments, conservation and variation, CpG islands, codon context, usage bias and phylogenetic inferences at whole genome and proteome level with user-friendly visual environment. Further, glycosylation sites and molecular diagnostic primers were also analyzed. Most importantly, we also proposed potential therapeutically imperative constituents namely vaccine epitopes, siRNAs, miRNAs, sgRNAs and repurposing drug candidates. PMID:27633273

  12. GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome.

    Science.gov (United States)

    Simovski, Boris; Vodák, Daniel; Gundersen, Sveinung; Domanska, Diana; Azab, Abdulrahman; Holden, Lars; Holden, Marit; Grytten, Ivar; Rand, Knut; Drabløs, Finn; Johansen, Morten; Mora, Antonio; Lund-Andersen, Christin; Fromm, Bastian; Eskeland, Ragnhild; Gabrielsen, Odd Stokke; Ferkingstad, Egil; Nakken, Sigve; Bengtsen, Mads; Nederbragt, Alexander Johan; Thorarensen, Hildur Sif; Akse, Johannes Andreas; Glad, Ingrid; Hovig, Eivind; Sandve, Geir Kjetil

    2017-07-01

    Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.

  13. LegumeIP: an integrative database for comparative genomics and transcriptomics of model legumes.

    Science.gov (United States)

    Li, Jun; Dai, Xinbin; Liu, Tingsong; Zhao, Patrick Xuechun

    2012-01-01

    Legumes play a vital role in maintaining the nitrogen cycle of the biosphere. They conduct symbiotic nitrogen fixation through endosymbiotic relationships with bacteria in root nodules. However, this and other characteristics of legumes, including mycorrhization, compound leaf development and profuse secondary metabolism, are absent in the typical model plant Arabidopsis thaliana. We present LegumeIP (http://plantgrn.noble.org/LegumeIP/), an integrative database for comparative genomics and transcriptomics of model legumes, for studying gene function and genome evolution in legumes. LegumeIP compiles gene and gene family information, syntenic and phylogenetic context and tissue-specific transcriptomic profiles. The database holds the genomic sequences of three model legumes, Medicago truncatula, Glycine max and Lotus japonicus plus two reference plant species, A. thaliana and Populus trichocarpa, with annotations based on UniProt, InterProScan, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases. LegumeIP also contains large-scale microarray and RNA-Seq-based gene expression data. Our new database is capable of systematic synteny analysis across M. truncatula, G. max, L. japonicas and A. thaliana, as well as construction and phylogenetic analysis of gene families across the five hosted species. Finally, LegumeIP provides comprehensive search and visualization tools that enable flexible queries based on gene annotation, gene family, synteny and relative gene expression.

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

    Directory of Open Access Journals (Sweden)

    Nina Ratna Djuita

    2010-11-01

    Full Text Available Genomic Integrity Detection of In Vitro Irradiated Banana Using Microsatellite Marker. The research aims todetect genomic integrity of in vitro irradiated banana using microsatellite marker. These studies were done on bananacv. Pisang Mas irradiated by 15 Gy of gamma ray. The DNA was isolated from each accesion following Dixie.Amplification of DNA products were done by Perkin Elmer Gene Amp PCR 2400 using ten primers, and thenelectroforesis in agarose 1%. Finally a vertical polyacrylamide gel electroforesis was run and the products werevisualized by silver staining. The result shown that among the primers tested, eight primers produced clear, discrete,and reproducible bands. Number of DNA band exhibited ranging from one to two, following the ploidy level of pisangMas which is a diploid banana cultivar (AA. One band suggest homozygote allele while two bands showedheterozygote allele. Out of eight primers, six primers produced different allele among irradiated, in vitro, and in vivocontrol plant. Meanwhile, for the other two primers the allele were monomorph for all the accessions examined.Genomic modification was observed at all irradiated plants. The modification can happened at zygosity of certain allelethat may change from heterozygote to homozygote or vice versa. While modification in allele size that underlyinggenomic instability could be caused by several genetic events such as deletion, insertion, and amplification ofnucleotides.

  15. Integrating experimental and analytic approaches to improve data quality in genome-wide RNAi screens.

    Science.gov (United States)

    Zhang, Xiaohua Douglas; Espeseth, Amy S; Johnson, Eric N; Chin, Jayne; Gates, Adam; Mitnaul, Lyndon J; Marine, Shane D; Tian, Jenny; Stec, Eric M; Kunapuli, Priya; Holder, Dan J; Heyse, Joseph F; Strulovici, Berta; Ferrer, Marc

    2008-06-01

    RNA interference (RNAi) not only plays an important role in drug discovery but can also be developed directly into drugs. RNAi high-throughput screening (HTS) biotechnology allows us to conduct genome-wide RNAi research. A central challenge in genome-wide RNAi research is to integrate both experimental and computational approaches to obtain high quality RNAi HTS assays. Based on our daily practice in RNAi HTS experiments, we propose the implementation of 3 experimental and analytic processes to improve the quality of data from RNAi HTS biotechnology: (1) select effective biological controls; (2) adopt appropriate plate designs to display and/or adjust for systematic errors of measurement; and (3) use effective analytic metrics to assess data quality. The applications in 5 real RNAi HTS experiments demonstrate the effectiveness of integrating these processes to improve data quality. Due to the effectiveness in improving data quality in RNAi HTS experiments, the methods and guidelines contained in the 3 experimental and analytic processes are likely to have broad utility in genome-wide RNAi research.

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

    Science.gov (United States)

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

    2013-12-12

    Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Identifying master regulators of cancer and their downstream targets by integrating genomic and epigenomic features.

    Science.gov (United States)

    Gevaert, Olivier; Plevritis, Sylvia

    2013-01-01

    Vast amounts of molecular data characterizing the genome, epigenome and transcriptome are becoming available for a variety of cancers. The current challenge is to integrate these diverse layers of molecular biology information to create a more comprehensive view of key biological processes underlying cancer. We developed a biocomputational algorithm that integrates copy number, DNA methylation, and gene expression data to study master regulators of cancer and identify their targets. Our algorithm starts by generating a list of candidate driver genes based on the rationale that genes that are driven by multiple genomic events in a subset of samples are unlikely to be randomly deregulated. We then select the master regulators from the candidate driver and identify their targets by inferring the underlying regulatory network of gene expression. We applied our biocomputational algorithm to identify master regulators and their targets in glioblastoma multiforme (GBM) and serous ovarian cancer. Our results suggest that the expression of candidate drivers is more likely to be influenced by copy number variations than DNA methylation. Next, we selected the master regulators and identified their downstream targets using module networks analysis. As a proof-of-concept, we show that the GBM and ovarian cancer module networks recapitulate known processes in these cancers. In addition, we identify master regulators that have not been previously reported and suggest their likely role. In summary, focusing on genes whose expression can be explained by their genomic and epigenomic aberrations is a promising strategy to identify master regulators of cancer.

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

    Directory of Open Access Journals (Sweden)

    Teck Yew Low

    2013-12-01

    Full Text Available Quantitative and qualitative protein characteristics are regulated at genomic, transcriptomic, and posttranscriptional levels. Here, we integrated in-depth transcriptome and proteome analyses of liver tissues from two rat strains to unravel the interactions within and between these layers. We obtained peptide evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83 splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data correlate highly between strains but poorly among each other, indicating extensive nongenetic regulation. Our multilevel analysis identified a genomic variant in the promoter of the most differentially expressed gene Cyp17a1, a previously reported top hit in genome-wide association studies for human hypertension, as a potential contributor to the hypertension phenotype in SHR rats. These results demonstrate the power of and need for integrative analysis for understanding genetic control of molecular dynamics and phenotypic diversity in a system-wide manner.

  19. Advances in the integration of transcriptional regulatory information into genome-scale metabolic models.

    Science.gov (United States)

    Vivek-Ananth, R P; Samal, Areejit

    2016-09-01

    A major goal of systems biology is to build predictive computational models of cellular metabolism. Availability of complete genome sequences and wealth of legacy biochemical information has led to the reconstruction of genome-scale metabolic networks in the last 15 years for several organisms across the three domains of life. Due to paucity of information on kinetic parameters associated with metabolic reactions, the constraint-based modelling approach, flux balance analysis (FBA), has proved to be a vital alternative to investigate the capabilities of reconstructed metabolic networks. In parallel, advent of high-throughput technologies has led to the generation of massive amounts of omics data on transcriptional regulation comprising mRNA transcript levels and genome-wide binding profile of transcriptional regulators. A frontier area in metabolic systems biology has been the development of methods to integrate the available transcriptional regulatory information into constraint-based models of reconstructed metabolic networks in order to increase the predictive capabilities of computational models and understand the regulation of cellular metabolism. Here, we review the existing methods to integrate transcriptional regulatory information into constraint-based models of metabolic networks.

  20. The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells

    Directory of Open Access Journals (Sweden)

    Swapna Kollu

    2015-06-01

    Full Text Available To ensure accurate genomic segregation, cells evolved the spindle assembly checkpoint (SAC, whose role in adult stem cells remains unknown. Inducible perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in skeletal muscle stem cells shows the SAC to be critical for normal muscle growth, repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting differentiation even under inductive conditions. p21CIP1 is responsible for these SAC-deficient phenotypes. Despite aneuploidy’s correlation with aging, we find that aged proliferating muscle stem cells display robust SAC activity without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to safeguard their genomic integrity. The SAC prevents chromosome missegregation and, if it fails, p21CIP1-dependent G1 arrest limits cellular propagation and tissue integration. These mechanisms ensure that muscle stem cells with compromised genomes do not contribute to tissue homeostasis.

  1. The importance of safeguarding genome integrity in germination and seed longevity.

    Science.gov (United States)

    Waterworth, Wanda M; Bray, Clifford M; West, Christopher E

    2015-06-01

    Seeds are important to agriculture and conservation of plant biodiversity. In agriculture, seed germination performance is an important determinant of crop yield, in particular under adverse climatic conditions. Deterioration in seed quality is associated with the accumulation of cellular damage to macromolecules including lipids, protein, and DNA. Mechanisms that mitigate the deleterious cellular damage incurred in the quiescent state and in cycles of desiccation-hydration are crucial for the maintenance of seed viability and germination vigour. In early-imbibing seeds, damage to the embryo genome must be repaired prior to initiation of cell division to minimize growth inhibition and mutation of genetic information. Here we review recent advances that have established molecular links between genome integrity and seed quality. These studies identified that maintenance of genome integrity is particularly important to the seed stage of the plant lifecycle, revealing new insight into the physiological roles of plant DNA repair and recombination mechanisms. The high conservation of DNA repair and recombination factors across plant species underlines their potential as promising targets for the improvement of crop performance and development of molecular markers for prediction of seed vigour.

  2. Genome-Wide Analysis of Alpharetroviral Integration in Human Hematopoietic Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Arianna Moiani

    2014-05-01

    Full Text Available Gene transfer vectors derived from gamma-retroviruses or lentiviruses are currently used for the gene therapy of genetic or acquired diseases. Retroviral vectors display a non-random integration pattern in the human genome, targeting either regulatory regions (gamma-retroviruses or the transcribed portion of expressed genes (lentiviruses, and have the potential to deregulate gene expression at the transcriptional or post-transcriptional level. A recently developed alternative vector system derives from the avian sarcoma-leukosis alpha-retrovirus (ASLV and shows favorable safety features compared to both gamma-retroviral and lentiviral vectors in preclinical models. We performed a high-throughput analysis of the integration pattern of self-inactivating (SIN alpha-retroviral vectors in human CD34+ hematopoietic stem/progenitor cells (HSPCs and compared it to previously reported gamma-retroviral and lentiviral vectors integration profiles obtained in the same experimental setting. Compared to gamma-retroviral and lentiviral vectors, the SIN-ASLV vector maintains a preference for open chromatin regions, but shows no bias for transcriptional regulatory elements or transcription units, as defined by genomic annotations and epigenetic markers (H3K4me1 and H3K4me3 histone modifications. Importantly, SIN-ASLV integrations do not cluster in hot spots and target potentially dangerous genomic loci, such as the EVI2A/B, RUNX1 and LMO2 proto-oncogenes at a virtually random frequency. These characteristics predict a safer profile for ASLV-derived vectors for clinical applications.

  3. Co-regulation of pluripotency and genetic integrity at the genomic level

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2014-11-01

    Full Text Available The Disposable Soma Theory holds that genetic integrity will be maintained at more pristine levels in germ cells than in somatic cells because of the unique role germ cells play in perpetuating the species. We tested the hypothesis that the same concept applies to pluripotent cells compared to differentiated cells. Analyses of transcriptome and cistrome databases, along with canonical pathway analysis and chromatin immunoprecipitation confirmed differential expression of DNA repair and cell death genes in embryonic stem cells and induced pluripotent stem cells relative to fibroblasts, and predicted extensive direct and indirect interactions between the pluripotency and genetic integrity gene networks in pluripotent cells. These data suggest that enhanced maintenance of genetic integrity is fundamentally linked to the epigenetic state of pluripotency at the genomic level. In addition, these findings demonstrate how a small number of key pluripotency factors can regulate large numbers of downstream genes in a pathway-specific manner.

  4. Advancing Post-Genome Data and System Integration Through Machine Learning

    Directory of Open Access Journals (Sweden)

    Francisco Azuaje

    2006-04-01

    Full Text Available Research on biological data integration has traditionally focused on the development of systems for the maintenance and interconnection of databases. In the next few years, public and private biotechnology organisations will expand their actions to promote the creation of a post-genome semantic web. It has commonly been accepted that artificial intelligence and data mining techniques may support the interpretation of huge amounts of integrated data. But at the same time, these research disciplines are contributing to the creation of content markup languages and sophisticated programs able to exploit the constraints and preferences of user domains. This paper discusses a number of issues on intelligent systems for the integration of bioinformatic resources.

  5. Genome Integration and Excision by a New Streptomyces Bacteriophage, ϕJoe.

    Science.gov (United States)

    Fogg, Paul C M; Haley, Joshua A; Stark, W Marshall; Smith, Margaret C M

    2017-03-01

    Bacteriophages are the source of many valuable tools for molecular biology and genetic manipulation. In Streptomyces, most DNA cloning vectors are based on serine integrase site-specific DNA recombination systems derived from phage. Because of their efficiency and simplicity, serine integrases are also used for diverse synthetic biology applications. Here, we present the genome of a new Streptomyces phage, ϕJoe, and investigate the conditions for integration and excision of the ϕJoe genome. ϕJoe belongs to the largest Streptomyces phage cluster (R4-like) and encodes a serine integrase. The attB site from Streptomyces venezuelae was used efficiently by an integrating plasmid, pCMF92, constructed using the ϕJoe int-attP locus. The attB site for ϕJoe integrase was occupied in several Streptomyces genomes, including that of S. coelicolor, by a mobile element that varies in gene content and size between host species. Serine integrases require a phage-encoded recombination directionality factor (RDF) to activate the excision reaction. The ϕJoe RDF was identified, and its function was confirmed in vivo Both the integrase and RDF were active in in vitro recombination assays. The ϕJoe site-specific recombination system is likely to be an important addition to the synthetic biology and genome engineering toolbox.IMPORTANCEStreptomyces spp. are prolific producers of secondary metabolites, including many clinically useful antibiotics. Bacteriophage-derived integrases are important tools for genetic engineering, as they enable integration of heterologous DNA into the Streptomyces chromosome with ease and high efficiency. Recently, researchers have been applying phage integrases for a variety of applications in synthetic biology, including rapid assembly of novel combinations of genes, biosensors, and biocomputing. An important requirement for optimal experimental design and predictability when using integrases, however, is the need for multiple enzymes with different

  6. Advances in environmental genomics: towards an integrated view of micro-organisms and ecosystems.

    Science.gov (United States)

    Bertin, Philippe N; Médigue, Claudine; Normand, Philippe

    2008-02-01

    Microbial genome sequencing has, for the first time, made accessible all the components needed for both the elaboration and the functioning of a cell. Associated with other global methods such as protein and mRNA profiling, genomics has considerably extended our knowledge of physiological processes and their diversity not only in human, animal and plant pathogens but also in environmental isolates. At a higher level of complexity, the so-called meta approaches have recently shown great promise in investigating microbial communities, including uncultured micro-organisms. Combined with classical methods of physico-chemistry and microbiology, these endeavours should provide us with an integrated view of how micro-organisms adapt to particular ecological niches and participate in the dynamics of ecosystems.

  7. Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets

    DEFF Research Database (Denmark)

    Swanton, C.; Larkin, J.M.; Gerlinger, M.

    2010-01-01

    RNA screens to identify and validate functionally important genomic or transcriptomic predictive biomarkers of individual drug response in patients. PREDICT's approach to predictive biomarker discovery differs from conventional associative learning approaches, which can be susceptible to the detection...... inhibitor. Through the analysis of tumour tissue derived from pre-operative renal cell carcinoma (RCC) clinical trials, the PREDICT consortium will use established and novel methods to integrate comprehensive tumour-derived genomic data with personalised tumour-derived shRNA and high throughput si......, reducing ineffective therapy in drug resistant disease, leading to improved quality of life and higher cost efficiency, which in turn should broaden patient access to beneficial therapeutics, thereby enhancing clinical outcome and cancer survival. The consortium will also establish and consolidate...

  8. Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar

    2016-01-01

    Full Text Available As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR, which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.

  9. Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Xiangjin Kang

    Full Text Available Human-induced pluripotent stem cells (iPSCs are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines", 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines", and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV, loss of heterozygosity (LOH and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic

  10. Effects of Integrating and Non-Integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kang, Xiangjin; Yu, Qian; Huang, Yuling; Song, Bing; Chen, Yaoyong; Gao, Xingcheng; He, Wenyin; Sun, Xiaofang; Fan, Yong

    2015-01-01

    Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines"), 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines"), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture) database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP) calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations

  11. 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.

  12. An integrated 4249 marker FISH/RH map of the canine genome

    Directory of Open Access Journals (Sweden)

    Mahairas Gregory G

    2004-09-01

    Full Text Available Abstract Background The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. Results To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH. The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS between the dog and human genomes, dramatically extending the length of most previously described CS. Conclusions These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps.

  13. Feature context-dependency and complexity-reduction in probability landscapes for integrative genomics

    Directory of Open Access Journals (Sweden)

    Benecke Arndt

    2008-09-01

    Full Text Available Abstract Background The question of how to integrate heterogeneous sources of biological information into a coherent framework that allows the gene regulatory code in eukaryotes to be systematically investigated is one of the major challenges faced by systems biology. Probability landscapes, which include as reference set the probabilistic representation of the genomic sequence, have been proposed as a possible approach to the systematic discovery and analysis of correlations amongst initially heterogeneous and un-relatable descriptions and genome-wide measurements. Much of the available experimental sequence and genome activity information is de facto, but not necessarily obviously, context dependent. Furthermore, the context dependency of the relevant information is itself dependent on the biological question addressed. It is hence necessary to develop a systematic way of discovering the context-dependency of functional genomics information in a flexible, question-dependent manner. Results We demonstrate here how feature context-dependency can be systematically investigated using probability landscapes. Furthermore, we show how different feature probability profiles can be conditionally collapsed to reduce the computational and formal, mathematical complexity of probability landscapes. Interestingly, the possibility of complexity reduction can be linked directly to the analysis of context-dependency. Conclusion These two advances in our understanding of the properties of probability landscapes not only simplify subsequent cross-correlation analysis in hypothesis-driven model building and testing, but also provide additional insights into the biological gene regulatory problems studied. Furthermore, insights into the nature of individual features and a classification of features according to their minimal context-dependency are achieved. The formal structure proposed contributes to a concrete and tangible basis for attempting to formulate novel

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

    Indian Academy of Sciences (India)

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

    2013-12-01

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

  15. Rice Annotation Project Database (RAP-DB): an integrative and interactive database for rice genomics.

    Science.gov (United States)

    Sakai, Hiroaki; Lee, Sung Shin; Tanaka, Tsuyoshi; Numa, Hisataka; Kim, Jungsok; Kawahara, Yoshihiro; Wakimoto, Hironobu; Yang, Ching-chia; Iwamoto, Masao; Abe, Takashi; Yamada, Yuko; Muto, Akira; Inokuchi, Hachiro; Ikemura, Toshimichi; Matsumoto, Takashi; Sasaki, Takuji; Itoh, Takeshi

    2013-02-01

    The Rice Annotation Project Database (RAP-DB, http://rapdb.dna.affrc.go.jp/) has been providing a comprehensive set of gene annotations for the genome sequence of rice, Oryza sativa (japonica group) cv. Nipponbare. Since the first release in 2005, RAP-DB has been updated several times along with the genome assembly updates. Here, we present our newest RAP-DB based on the latest genome assembly, Os-Nipponbare-Reference-IRGSP-1.0 (IRGSP-1.0), which was released in 2011. We detected 37,869 loci by mapping transcript and protein sequences of 150 monocot species. To provide plant researchers with highly reliable and up to date rice gene annotations, we have been incorporating literature-based manually curated data, and 1,626 loci currently incorporate literature-based annotation data, including commonly used gene names or gene symbols. Transcriptional activities are shown at the nucleotide level by mapping RNA-Seq reads derived from 27 samples. We also mapped the Illumina reads of a Japanese leading japonica cultivar, Koshihikari, and a Chinese indica cultivar, Guangluai-4, to the genome and show alignments together with the single nucleotide polymorphisms (SNPs) and gene functional annotations through a newly developed browser, Short-Read Assembly Browser (S-RAB). We have developed two satellite databases, Plant Gene Family Database (PGFD) and Integrative Database of Cereal Gene Phylogeny (IDCGP), which display gene family and homologous gene relationships among diverse plant species. RAP-DB and the satellite databases offer simple and user-friendly web interfaces, enabling plant and genome researchers to access the data easily and facilitating a broad range of plant research topics.

  16. 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.

  17. Perspectives on clinical informatics: integrating large-scale clinical, genomic, and health information for clinical care.

    Science.gov (United States)

    Choi, In Young; Kim, Tae-Min; Kim, Myung Shin; Mun, Seong K; Chung, Yeun-Jun

    2013-12-01

    The advances in electronic medical records (EMRs) and bioinformatics (BI) represent two significant trends in healthcare. The widespread adoption of EMR systems and the completion of the Human Genome Project developed the technologies for data acquisition, analysis, and visualization in two different domains. The massive amount of data from both clinical and biology domains is expected to provide personalized, preventive, and predictive healthcare services in the near future. The integrated use of EMR and BI data needs to consider four key informatics areas: data modeling, analytics, standardization, and privacy. Bioclinical data warehouses integrating heterogeneous patient-related clinical or omics data should be considered. The representative standardization effort by the Clinical Bioinformatics Ontology (CBO) aims to provide uniquely identified concepts to include molecular pathology terminologies. Since individual genome data are easily used to predict current and future health status, different safeguards to ensure confidentiality should be considered. In this paper, we focused on the informatics aspects of integrating the EMR community and BI community by identifying opportunities, challenges, and approaches to provide the best possible care service for our patients and the population.

  18. Development and clinical application of an integrative genomic approach to personalized cancer therapy.

    Science.gov (United States)

    Uzilov, Andrew V; Ding, Wei; Fink, Marc Y; Antipin, Yevgeniy; Brohl, Andrew S; Davis, Claire; Lau, Chun Yee; Pandya, Chetanya; Shah, Hardik; Kasai, Yumi; Powell, James; Micchelli, Mark; Castellanos, Rafael; Zhang, Zhongyang; Linderman, Michael; Kinoshita, Yayoi; Zweig, Micol; Raustad, Katie; Cheung, Kakit; Castillo, Diane; Wooten, Melissa; Bourzgui, Imane; Newman, Leah C; Deikus, Gintaras; Mathew, Bino; Zhu, Jun; Glicksberg, Benjamin S; Moe, Aye S; Liao, Jun; Edelmann, Lisa; Dudley, Joel T; Maki, Robert G; Kasarskis, Andrew; Holcombe, Randall F; Mahajan, Milind; Hao, Ke; Reva, Boris; Longtine, Janina; Starcevic, Daniela; Sebra, Robert; Donovan, Michael J; Li, Shuyu; Schadt, Eric E; Chen, Rong

    2016-06-01

    Personalized therapy provides the best outcome of cancer care and its implementation in the clinic has been greatly facilitated by recent convergence of enormous progress in basic cancer research, rapid advancement of new tumor profiling technologies, and an expanding compendium of targeted cancer therapeutics. We developed a personalized cancer therapy (PCT) program in a clinical setting, using an integrative genomics approach to fully characterize the complexity of each tumor. We carried out whole exome sequencing (WES) and single-nucleotide polymorphism (SNP) microarray genotyping on DNA from tumor and patient-matched normal specimens, as well as RNA sequencing (RNA-Seq) on available frozen specimens, to identify somatic (tumor-specific) mutations, copy number alterations (CNAs), gene expression changes, gene fusions, and also germline variants. To provide high sensitivity in known cancer mutation hotspots, Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2) was also employed. We integrated the resulting data with cancer knowledge bases and developed a specific workflow for each cancer type to improve interpretation of genomic data. We returned genomics findings to 46 patients and their physicians describing somatic alterations and predicting drug response, toxicity, and prognosis. Mean 17.3 cancer-relevant somatic mutations per patient were identified, 13.3-fold, 6.9-fold, and 4.7-fold more than could have been detected using CHPv2, Oncomine Cancer Panel (OCP), and FoundationOne, respectively. Our approach delineated the underlying genetic drivers at the pathway level and provided meaningful predictions of therapeutic efficacy and toxicity. Actionable alterations were found in 91 % of patients (mean 4.9 per patient, including somatic mutations, copy number alterations, gene expression alterations, and germline variants), a 7.5-fold, 2.0-fold, and 1.9-fold increase over what could have been uncovered by CHPv2, OCP, and FoundationOne, respectively. The findings altered

  19. 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

  20. 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.

  1. MicroScope in 2017: an expanding and evolving integrated resource for community expertise of microbial genomes

    Science.gov (United States)

    Vallenet, David; Calteau, Alexandra; Cruveiller, Stéphane; Gachet, Mathieu; Lajus, Aurélie; Josso, Adrien; Mercier, Jonathan; Renaux, Alexandre; Rollin, Johan; Rouy, Zoe; Roche, David; Scarpelli, Claude; Médigue, Claudine

    2017-01-01

    The annotation of genomes from NGS platforms needs to be automated and fully integrated. However, maintaining consistency and accuracy in genome annotation is a challenging problem because millions of protein database entries are not assigned reliable functions. This shortcoming limits the knowledge that can be extracted from genomes and metabolic models. Launched in 2005, the MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Effective comparative analysis requires a consistent and complete view of biological data, and therefore, support for reviewing the quality of functional annotation is critical. MicroScope allows users to analyze microbial (meta)genomes together with post-genomic experiment results if any (i.e. transcriptomics, re-sequencing of evolved strains, mutant collections, phenotype data). It combines tools and graphical interfaces to analyze genomes and to perform the expert curation of gene functions in a comparative context. Starting with a short overview of the MicroScope system, this paper focuses on some major improvements of the Web interface, mainly for the submission of genomic data and on original tools and pipelines that have been developed and integrated in the platform: computation of pan-genomes and prediction of biosynthetic gene clusters. Today the resource contains data for more than 6000 microbial genomes, and among the 2700 personal accounts (65% of which are now from foreign countries), 14% of the users are performing expert annotations, on at least a weekly basis, contributing to improve the quality of microbial genome annotations. PMID:27899624

  2. Accurate Localization of the Integration Sites of Two Genomic Islands at Single-Nucleotide Resolution in the Genome of Bacillus cereus ATCC 10987

    Directory of Open Access Journals (Sweden)

    Ren Zhang

    2008-01-01

    Full Text Available We have identified two genomic islands, that is, BCEGI-1 and BCEGI-2, in the genome of Bacillus cereus ATCC 10987, based on comparative analysis with Bacillus cereus ATCC 14579. Furthermore, by using the cumulative GC profile and performing homology searches between the two genomes, the integration sites of the two genomic islands were determined at single-nucleotide resolution. BCEGI-1 is integrated between 159705 bp and 198000 bp, whereas BCEGI-2 is integrated between the end of ORF BCE4594 and the start of the intergenic sequence immediately following BCE4626, that is, from 4256803 bp to 4285534 bp. BCEGI-1 harbors two bacterial Tn7 transposons, which have two sets of genes encoding TnsA, B, C, and D. It is generally believed that unlike the TnsABC+E pathway, the TnsABC+D pathway would only promote vertical transmission to daughter cells. The evidence presented in this paper, however, suggests a role of the TnsABC+D pathway in the horizontal transfer of some genomic islands.

  3. Gramene database: Navigating plant comparative genomics resources

    Directory of Open Access Journals (Sweden)

    Parul Gupta

    2016-11-01

    Full Text Available Gramene (http://www.gramene.org is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationships to enrich the annotation of genomic data and provides tools to perform powerful comparative analyses across a wide spectrum of plant species. It consists of an integrated portal for querying, visualizing and analyzing data for 44 plant reference genomes, genetic variation data sets for 12 species, expression data for 16 species, curated rice pathways and orthology-based pathway projections for 66 plant species including various crops. Here we briefly describe the functions and uses of the Gramene database.

  4. Intelligent geospatial data retrieval based on the geospatial grid portal

    Science.gov (United States)

    Yuan, Jie; Yue, Peng; Gong, Jianya

    2008-12-01

    The Open Geospatial Consortium (OGC) standard-compliant services define a set of standard interfaces for geospatial Web services to achieve the interoperability in an open distributed computing environment. Grid technology is a distributed computing infrastructure to allow distributed resources sharing and coordinated problem solving. Based on the OGC standards for geospatial services and grid technology, we propose the geospatial grid portal to integrate and interoperate grid-enabled geospatial services. The implementation of the geospatial grid portal is based on a three-tier architecture which consists of grid-enabled geospatial services tier, grid service portal tier and application tier. The OGC standard-compliant services are deployed in a grid environment, the so-called grid-enabled geospatial services. Grid service portals for each type of geospatial services, including WFS, WMS, WCS and CSW, provide a single point of Web entry to discover and access different types of geospatial information. A resource optimization mechanism is incorporated into these service portals to optimize the selection of grid nodes. At the top tier, i.e. the application tier, the client interacts with a semantic middleware for the grid CSW portal, thus allows the semantics-enabled search. The proposed approach can not only optimize the grid resource selection among multiple grid nodes, but also incorporate the power of Semantic Web technology into geospatial grid portal to allow the precise discovery of geospatial data.

  5. Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration.

    Directory of Open Access Journals (Sweden)

    Aviad Levin

    Full Text Available BACKGROUND: The human immunodeficiency virus type 1 (HIV-1 integrase protein (IN, catalyzes the integration of viral DNA into the host cell genome. IN catalyzes the first step of the integration process, namely the 3'-end processing in which IN removes a pGT dinucleotide from the 3' end of each viral long terminal repeat (LTR. Following nuclear import of the viral preintegration complex, the host chromosomal DNA becomes accessible to the viral cDNA and the second step of the integration process, namely the strand-transfer step takes place. This ordered sequence of events, centered on integration, is mandatory for HIV replication. METHODOLOGY/PRINCIPAL FINDINGS: Using an integrase peptide library, we selected two peptides, designated INr-1 and INr-2, which interact with the Rev protein and probably mediate the Rev-integrase interaction. Using an in-vitro assay system, we show that INr-1 and INr-2 are able to abrogate the inhibitory effects exerted by Rev and Rev-derived peptides on integrase activity. Both INr-1 and INr-2 were found to be cell-permeable and nontoxic, allowing a study of their effect in HIV-1-infected cultured cells. Interestingly, both INr peptides stimulated virus infectivity as estimated by production of the viral P24 protein, as well as by determination of the appearance of newly formed virus particles. Furthermore, kinetics studies revealed that the cell-permeable INr peptides enhance the integration process, as was indeed confirmed by direct determination of viral DNA integration by real-time PCR. CONCLUSIONS/SIGNIFICANCE: The results of the present study raise the possibility that in HIV-infected cells, the Rev protein may be involved in the integration of proviral DNA by controlling/regulating the activity of the integrase. Release from such inhibition leads to stimulation of IN activity and multiple viral DNA integration events.

  6. CCI Open Data Portal

    Science.gov (United States)

    Clarke, H.; Pechorro, E.; Bennett, V.; Farquhar, C.; Blower, J.

    2016-08-01

    The European Space Agency's (ESA's) Climate Change Initiative (CCI) Programme, producing harmonised datasets from long term Earth Observation satellite data records for a number of Essential Climate Variables (ECV's), provides a solid basis for climate science and modelling, for specialist application development and ultimately for European and global policy making.The resulting Climate Data Records (CDRs) represent a major investment of science, funding and personal effort, therefore extended access to those products is a key element of programme success.ECV datasets are currently being distributed through individual ECV teams, and access procedures and interfaces vary. To compliment and unify the work of the individual teams and to maximise the visibility and uptake of ECV data in the climate data user community within and beyond the CCI, a new ESA CCI project has started, to create a central open data portal and metadata catalogue for the ESA CCI project.This paper highlights key features of the Portal to date.

  7. Fueling the Future with Fungal Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2014-10-27

    Genomes of fungi relevant to energy and environment are in focus of the JGI Fungal Genomic Program. One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts and pathogens) and biorefinery processes (cellulose degradation and sugar fermentation) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Science Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 400 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics will lead to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such ‘parts’ suggested by comparative genomics and functional analysis in these areas are presented here.

  8. Portal Vein Thrombosis in non cirrhotic patients

    NARCIS (Netherlands)

    M.C.W. Spaander (Manon)

    2010-01-01

    textabstractExtrahepatic portal vein thrombosis (EPVT) is the most common cause of portal hypertension in non- cirrhotic patients. EPVT has been defined as an obstruction of the extrahepatic portal vein with or without involvement of the intrahepatic portal veins. Although the portal vein accounts f

  9. A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for canine cancer studies and comparative genomic analysis.

    Science.gov (United States)

    Thomas, R; Duke, S E; Karlsson, E K; Evans, A; Ellis, P; Lindblad-Toh, K; Langford, C F; Breen, M

    2008-01-01

    Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.

  10. Portal hypertensive enteropathy

    Institute of Scientific and Technical Information of China (English)

    Parit Mekaroonkamol; Robert Cohen; Saurabh Chawla

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a conditionthat describes the pathologic changes and mucosalabnormalities observed in the small intestine of patientswith portal hypertension. This entity is being increasinglyrecognized and better understood over the past decadedue to increased accessibility of the small intestine madepossible by the introduction of video capsule endoscopyand deep enteroscopy. Though challenged by its diverseendoscopic appearance, multiple scoring systems havebeen proposed to classify the endoscopic presentationand grade its severity. Endoscopic findings can be broadlycategorized into vascular and non-vascular lesions withmany subtypes of both categories. Clinical manifestationsof PHE can range from asymptomatic incidental findingsto fatal gastrointestinal hemorrhage. Classic endoscopicfindings in the setting of portal hypertension may leadto a prompt diagnosis. Occasionally histopathologyand cross sectional imaging like computed tomographyor magnetic resonance imaging may be helpful inestablishing a diagnosis. Management of overt bleedingrequires multidisciplinary approach involving hepatologists,endoscopists, surgeons, and interventionalradiologists. Adequate resuscitation, reduction of portalpressure, and endoscopic therapeutic intervention remainthe main principles of the initial treatment. This articlereviews the existing evidence on PHE with emphasison its classification, diagnosis, clinical manifestations,endoscopic appearance, pathological findings, and clinicalmanagement. A new schematic management of ectopicvariceal bleed is also proposed.

  11. Portal Annular Pancreas

    Science.gov (United States)

    Harnoss, Jonathan M.; Harnoss, Julian C.; Diener, Markus K.; Contin, Pietro; Ulrich, Alexis B.; Büchler, Markus W.; Schmitz-Winnenthal, Friedrich H.

    2014-01-01

    Abstract Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option. PMID:25207658

  12. Conjugative Transfer and cis-Mobilization of a Genomic Island by an Integrative and Conjugative Element of Streptococcus agalactiae

    OpenAIRE

    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie

    2013-01-01

    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913–6917, 2008). We investigated here the mobility of the elements integrated into the 3′ end of a tRNALys gene. Three of the four putative ICEs tested were found to ...

  13. Improving biological understanding and complex trait prediction by integrating prior information in genomic feature models

    DEFF Research Database (Denmark)

    Edwards, Stefan McKinnon

    externally founded information, such as KEGG pathways, Gene Ontology gene sets, or genomic features, and estimate the joint contribution of the genetic variants within these sets to complex trait phenotypes. The analysis of complex trait phenotypes is hampered by the myriad of genes that control the trait......In this thesis we investigate an approach to integrate external data into the analysis of genetic variants. The goal is similar to that of gene-set enrichment tests, but relies on the robust statistical framework of linear mixed models. This approach has allowed us to integrate virtually any......, as these genes have small to moderate effects that can be difficult to detect. However, by looking at sets of genes, as in gene-set enrichment tests, it may become easier to assess an association between the set of genes and the complex trait. ---  The linear mixed models applied here are the same as used...

  14. Genome scale models of yeast: towards standardized evaluation and consistent omic integration

    DEFF Research Database (Denmark)

    Sanchez, Benjamin J.; Nielsen, Jens

    2015-01-01

    Genome scale models (GEMs) have enabled remarkable advances in systems biology, acting as functional databases of metabolism, and as scaffolds for the contextualization of high-throughput data. In the case of Saccharomyces cerevisiae (budding yeast), several GEMs have been published...... and are currently used for metabolic engineering and elucidating biological interactions. Here we review the history of yeast's GEMs, focusing on recent developments. We study how these models are typically evaluated, using both descriptive and predictive metrics. Additionally, we analyze the different ways...... in which all levels of omics data (from gene expression to flux) have been integrated in yeast GEMs. Relevant conclusions and current challenges for both GEM evaluation and omic integration are highlighted....

  15. Integration of gene expression data into genome-scale metabolic models

    DEFF Research Database (Denmark)

    Åkesson, M.; Förster, Jochen; Nielsen, Jens

    2004-01-01

    of gene expression from chemostat and batch cultures of Saccharomyces cerevisiae were combined with a recently developed genome-scale model, and the computed metabolic flux distributions were compared to experimental values from carbon labeling experiments and metabolic network analysis. The integration......A framework for integration of transcriptome data into stoichiometric metabolic models to obtain improved flux predictions is presented. The key idea is to exploit the regulatory information in the expression data to give additional constraints on the metabolic fluxes in the model. Measurements...... of expression data resulted in improved predictions of metabolic behavior in batch cultures, enabling quantitative predictions of exchange fluxes as well as qualitative estimations of changes in intracellular fluxes. A critical discussion of correlation between gene expression and metabolic fluxes is given....

  16. Application of integrative genomics and systems biology to conventional and in vitro reproductive traits in cattle

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Pedersen, Hanne S.; de Oliveira Junior, Gerson A.

    2017-01-01

    by both conventional and ARTs such as OPU-IVP. The integration of systems biology information across different biological layers generates a complete view of the different molecular networks that control complex traits and can provide a strong contribution to the understanding of traits related to ARTs....... donor and embryo recipient quality is needed to make realistic a commercialization of these procedures in the near future. A better understanding of both biological mechanisms and molecular markers associated to IVPET related traits is necessary to improve the prediction of donor and recipient cow...... quality for IVP procedures. The huge amount of data generated from high throughput technologies has a tremendous impact in the search for biomarkers of complex traits. This paper reviews integrative genomics and systems biology approaches as applied to both Bos indicus and Bos taurus cattle reproduction...

  17. GFVO: the Genomic Feature and Variation Ontology.

    Science.gov (United States)

    Baran, Joachim; Durgahee, Bibi Sehnaaz Begum; Eilbeck, Karen; Antezana, Erick; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Falling costs in genomic laboratory experiments have led to a steady increase of genomic feature and variation data. Multiple genomic data formats exist for sharing these data, and whilst they are similar, they are addressing slightly different data viewpoints and are consequently not fully compatible with each other. The fragmentation of data format specifications makes it hard to integrate and interpret data for further analysis with information from multiple data providers. As a solution, a new ontology is presented here for annotating and representing genomic feature and variation dataset contents. The Genomic Feature and Variation Ontology (GFVO) specifically addresses genomic data as it is regularly shared using the GFF3 (incl. FASTA), GTF, GVF and VCF file formats. GFVO simplifies data integration and enables linking of genomic annotations across datasets through common semantics of genomic types and relations. Availability and implementation. The latest stable release of the ontology is available via its base URI; previous and development versions are available at the ontology's GitHub repository: https://github.com/BioInterchange/Ontologies; versions of the ontology are indexed through BioPortal (without external class-/property-equivalences due to BioPortal release 4.10 limitations); examples and reference documentation is provided on a separate web-page: http://www.biointerchange.org/ontologies.html. GFVO version 1.0.2 is licensed under the CC0 1.0 Universal license (https://creativecommons.org/publicdomain/zero/1.0) and therefore de facto within the public domain; the ontology can be appropriated without attribution for commercial and non-commercial use.

  18. GFVO: the Genomic Feature and Variation Ontology

    KAUST Repository

    Baran, Joachim

    2015-05-05

    Falling costs in genomic laboratory experiments have led to a steady increase of genomic feature and variation data. Multiple genomic data formats exist for sharing these data, and whilst they are similar, they are addressing slightly different data viewpoints and are consequently not fully compatible with each other. The fragmentation of data format specifications makes it hard to integrate and interpret data for further analysis with information from multiple data providers. As a solution, a new ontology is presented here for annotating and representing genomic feature and variation dataset contents. The Genomic Feature and Variation Ontology (GFVO) specifically addresses genomic data as it is regularly shared using the GFF3 (incl. FASTA), GTF, GVF and VCF file formats. GFVO simplifies data integration and enables linking of genomic annotations across datasets through common semantics of genomic types and relations. Availability and implementation. The latest stable release of the ontology is available via its base URI; previous and development versions are available at the ontology’s GitHub repository: https://github.com/BioInterchange/Ontologies; versions of the ontology are indexed through BioPortal (without external class-/property-equivalences due to BioPortal release 4.10 limitations); examples and reference documentation is provided on a separate web-page: http://www.biointerchange.org/ontologies.html. GFVO version 1.0.2 is licensed under the CC0 1.0 Universal license (https://creativecommons.org/publicdomain/zero/1.0) and therefore de facto within the public domain; the ontology can be appropriated without attribution for commercial and non-commercial use.

  19. GFVO: the Genomic Feature and Variation Ontology

    Directory of Open Access Journals (Sweden)

    Joachim Baran

    2015-05-01

    Full Text Available Falling costs in genomic laboratory experiments have led to a steady increase of genomic feature and variation data. Multiple genomic data formats exist for sharing these data, and whilst they are similar, they are addressing slightly different data viewpoints and are consequently not fully compatible with each other. The fragmentation of data format specifications makes it hard to integrate and interpret data for further analysis with information from multiple data providers. As a solution, a new ontology is presented here for annotating and representing genomic feature and variation dataset contents. The Genomic Feature and Variation Ontology (GFVO specifically addresses genomic data as it is regularly shared using the GFF3 (incl. FASTA, GTF, GVF and VCF file formats. GFVO simplifies data integration and enables linking of genomic annotations across datasets through common semantics of genomic types and relations.Availability and implementation. The latest stable release of the ontology is available via its base URI; previous and development versions are available at the ontology’s GitHub repository: https://github.com/BioInterchange/Ontologies; versions of the ontology are indexed through BioPortal (without external class-/property-equivalences due to BioPortal release 4.10 limitations; examples and reference documentation is provided on a separate web-page: http://www.biointerchange.org/ontologies.html. GFVO version 1.0.2 is licensed under the CC0 1.0 Universal license (https://creativecommons.org/publicdomain/zero/1.0 and therefore de facto within the public domain; the ontology can be appropriated without attribution for commercial and non-commercial use.

  20. 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.

  1. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

    OpenAIRE

    Barnes, Ryan; Eckert, Kristin

    2017-01-01

    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome ...

  2. 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.

  3. 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

  4. Purdue Ionomics Information Management System. An Integrated Functional Genomics Platform1[C][W][OA

    Science.gov (United States)

    Baxter, Ivan; Ouzzani, Mourad; Orcun, Seza; Kennedy, Brad; Jandhyala, Shrinivas S.; Salt, David E.

    2007-01-01

    The advent of high-throughput phenotyping technologies has created a deluge of information that is difficult to deal with without the appropriate data management tools. These data management tools should integrate defined workflow controls for genomic-scale data acquisition and validation, data storage and retrieval, and data analysis, indexed around the genomic information of the organism of interest. To maximize the impact of these large datasets, it is critical that they are rapidly disseminated to the broader research community, allowing open access for data mining and discovery. We describe here a system that incorporates such functionalities developed around the Purdue University high-throughput ionomics phenotyping platform. The Purdue Ionomics Information Management System (PiiMS) provides integrated workflow control, data storage, and analysis to facilitate high-throughput data acquisition, along with integrated tools for data search, retrieval, and visualization for hypothesis development. PiiMS is deployed as a World Wide Web-enabled system, allowing for integration of distributed workflow processes and open access to raw data for analysis by numerous laboratories. PiiMS currently contains data on shoot concentrations of P, Ca, K, Mg, Cu, Fe, Zn, Mn, Co, Ni, B, Se, Mo, Na, As, and Cd in over 60,000 shoot tissue samples of Arabidopsis (Arabidopsis thaliana), including ethyl methanesulfonate, fast-neutron and defined T-DNA mutants, and natural accession and populations of recombinant inbred lines from over 800 separate experiments, representing over 1,000,000 fully quantitative elemental concentrations. PiiMS is accessible at www.purdue.edu/dp/ionomics. PMID:17189337

  5. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Science.gov (United States)

    van der Lee, Robin; Feng, Qian; Langereis, Martijn A; Ter Horst, Rob; Szklarczyk, Radek; Netea, Mihai G; Andeweg, Arno C; van Kuppeveld, Frank J M; Huynen, Martijn A

    2015-10-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50%) that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1), and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1). Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/), obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

  6. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2015-10-01

    Full Text Available The RIG-I-like receptor (RLR pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50% that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1, and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1. Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/, obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

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

    Science.gov (United States)

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

    2014-04-01

    Recent advances in high-throughput sequencing (HTS) technologies and computing capacity have produced unprecedented amounts of genomic data that have unraveled the genetics of phenotypic variability in several species. However, operating and integrating current software tools for data analysis still require important investments in highly skilled personnel. Developing accurate, efficient and user-friendly software packages for HTS data analysis will lead to a more rapid discovery of genomic elements relevant to medical, agricultural and industrial applications. We therefore developed Next-Generation Sequencing Eclipse Plug-in (NGSEP), a new software tool for integrated, efficient and user-friendly detection of single nucleotide variants (SNVs), indels and copy number variants (CNVs). NGSEP includes modules for read alignment, sorting, merging, functional annotation of variants, filtering and quality statistics. Analysis of sequencing experiments in yeast, rice and human samples shows that NGSEP has superior accuracy and efficiency, compared with currently available packages for variants detection. We also show that only a comprehensive and accurate identification of repeat regions and CNVs allows researchers to properly separate SNVs from differences between copies of repeat elements. We expect that NGSEP will become a strong support tool to empower the analysis of sequencing data in a wide range of research projects on different species.

  8. Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes

    Indian Academy of Sciences (India)

    Indraneel Mittra; Naveen Kumar Khare; Gorantla Venkata Raghuram; Rohan Chaubal; Fatema Khambatti; Deepika Gupta; Ashwini Gaikwad; Preeti Prasannan; Akshita Singh; Aishwarya Iyer; Ankita Singh; Pawan Upadhyay; Naveen Kumar Nair; Pradyumna Kumar Mishra; Amit Dutt

    2015-03-01

    Whether nucleic acids that circulate in blood have any patho-physiological functions in the host have not been explored. We report here that far from being inert molecules, circulating nucleic acids have significant biological activities of their own that are deleterious to healthy cells of the body. Fragmented DNA and chromatin (DNAfs and Cfs) isolated from blood of cancer patients and healthy volunteers are readily taken up by a variety of cells in culture to be localized in their nuclei within a few minutes. The intra-nuclear DNAfs and Cfs associate themselves with host cell chromosomes to evoke a cellular DNA-damage-repair-response (DDR) followed by their incorporation into the host cell genomes. Whole genome sequencing detected the presence of tens of thousands of human sequence reads in the recipient mouse cells. Genomic incorporation of DNAfs and Cfs leads to dsDNA breaks and activation of apoptotic pathways in the treated cells. When injected intravenously into Balb/C mice, DNAfs and Cfs undergo genomic integration into cells of their vital organs resulting in activation of DDR and apoptotic proteins in the recipient cells. Cfs have significantly greater activity than DNAfs with respect to all parameters examined, while both DNAfs and Cfs isolated from cancer patients are more active than those from normal volunteers. All the above pathological actions of DNAfs and Cfs described above can be abrogated by concurrent treatment with DNase I and/or anti-histone antibody complexed nanoparticles both in vitro and in vivo. Taken together, our results that circulating DNAfs and Cfs are physiological, continuously arising, endogenous DNA damaging agents with implications to ageing and a multitude of human pathologies including initiation of cancer.

  9. Genetic control of flowering time in rice: integration of Mendelian genetics and genomics.

    Science.gov (United States)

    Hori, Kiyosumi; Matsubara, Kazuki; Yano, Masahiro

    2016-12-01

    Integration of previous Mendelian genetic analyses and recent molecular genomics approaches, such as linkage mapping and QTL cloning, dramatically strengthened our current understanding of genetic control of rice flowering time. Flowering time is one of the most important agronomic traits for seed production in rice (Oryza sativa L.). It is controlled mainly by genes associated with photoperiod sensitivity, particularly in short-day plants such as rice. Since the early twentieth century, rice breeders and researchers have been interested in elucidating the genetic basis of flowering time because its modification is important for regional adaptation and yield optimization. Although flowering time is a complex trait controlled by many quantitative trait loci (QTLs), classical genetic studies have shown that many associated genes are inherited in accordance with Mendelian laws. Decoding the rice genome sequence opened a new era in understanding the genetic control of flowering time on the basis of genome-wide mapping and gene cloning. Heading date 1 (Hd1) was the first flowering time QTL to be isolated using natural variation in rice. Recent accumulation of information on rice genome has facilitated the cloning of other QTLs, including those with minor effects on flowering time. This information has allowed us to rediscover some of the flowering genes that were identified by classical Mendelian genetics. The genes characterized so far, including Hd1, have been assigned to specific photoperiod pathways. In this review, we provide an overview of the studies that led to an in-depth understanding of the genetic control of flowering time in rice, and of the current state of improving and fine-tuning this trait for rice breeding.

  10. USGS Urban Waters Portal Overview

    Science.gov (United States)

    This presentation discusses urbanization and water quality trends, major stories on contaminants and biota, scientific and educational tools for watershed organizations, and the USGS Urban Waters Portal.

  11. Animal models of portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Juan G Abraldes; Marcos Pasarín; Juan Carlos; García-Pagán

    2006-01-01

    Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model,depending on the specific objectives of the study, are also discussed.

  12. Wireless Sensor Portal Technology Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Recognizing the needs and challenges facing NASA Earth Science for data input, manipulation and distribution, Mobitrum is proposing a ? Wireless Sensor Portal...

  13. An integrative genomic and epigenomic approach for the study of transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Maria E Figueroa

    Full Text Available The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis and developing new targeted-therapies. Aberrant gene regulation is a hallmark of cancer and plays a central role in determining tumor phenotype. We predicted that integration of different genome-wide epigenetic regulatory marks along with gene expression levels would provide greater power in capturing biological differences between leukemia subtypes. Gene expression, cytosine methylation and histone H3 lysine 9 (H3K9 acetylation were measured using high-density oligonucleotide microarrays in primary human acute myeloid leukemia (AML and acute lymphocytic leukemia (ALL specimens. We found that DNA methylation and H3K9 acetylation distinguished these leukemias of distinct cell lineage, as expected, but that an integrative analysis combining the information from each platform revealed hundreds of additional differentially expressed genes that were missed by gene expression arrays alone. This integrated analysis also enhanced the detection and statistical significance of biological pathways dysregulated in AML and ALL. Integrative epigenomic studies are thus feasible using clinical samples and provide superior detection of aberrant transcriptional programming than single-platform microarray studies.

  14. Genome-wide conserved non-coding microsatellite (CNMS) marker-based integrative genetical genomics for quantitative dissection of seed weight in chickpea

    Science.gov (United States)

    Bajaj, Deepak; Saxena, Maneesha S.; Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Tripathi, Shailesh; Upadhyaya, Hari D.; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    Phylogenetic footprinting identified 666 genome-wide paralogous and orthologous CNMS (conserved non-coding microsatellite) markers from 5′-untranslated and regulatory regions (URRs) of 603 protein-coding chickpea genes. The (CT)n and (GA)n CNMS carrying CTRMCAMV35S and GAGA8BKN3 regulatory elements, respectively, are abundant in the chickpea genome. The mapped genic CNMS markers with robust amplification efficiencies (94.7%) detected higher intraspecific polymorphic potential (37.6%) among genotypes, implying their immense utility in chickpea breeding and genetic analyses. Seventeen differentially expressed CNMS marker-associated genes showing strong preferential and seed tissue/developmental stage-specific expression in contrasting genotypes were selected to narrow down the gene targets underlying seed weight quantitative trait loci (QTLs)/eQTLs (expression QTLs) through integrative genetical genomics. The integration of transcript profiling with seed weight QTL/eQTL mapping, molecular haplotyping, and association analyses identified potential molecular tags (GAGA8BKN3 and RAV1AAT regulatory elements and alleles/haplotypes) in the LOB-domain-containing protein- and KANADI protein-encoding transcription factor genes controlling the cis-regulated expression for seed weight in the chickpea. This emphasizes the potential of CNMS marker-based integrative genetical genomics for the quantitative genetic dissection of complex seed weight in chickpea. PMID:25504138

  15. OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

    Directory of Open Access Journals (Sweden)

    John Orechia

    2015-09-01

    Full Text Available We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS and a suite of tools called Oncology Data Retrieval Systems (OncDRS. OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies.

  16. AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.

    Science.gov (United States)

    Martin, Olivier; Valsesia, Armand; Telenti, Amalio; Xenarios, Ioannis; Stevenson, Brian J

    2009-03-01

    We present a tool designed for visualization of large-scale genetic and genomic data exemplified by results from genome-wide association studies. This software provides an integrated framework to facilitate the interpretation of SNP association studies in genomic context. Gene annotations can be retrieved from Ensembl, linkage disequilibrium data downloaded from HapMap and custom data imported in BED or WIG format. AssociationViewer integrates functionalities that enable the aggregation or intersection of data tracks. It implements an efficient cache system and allows the display of several, very large-scale genomic datasets. The Java code for AssociationViewer is distributed under the GNU General Public Licence and has been tested on Microsoft Windows XP, MacOSX and GNU/Linux operating systems. It is available from the SourceForge repository. This also includes Java webstart, documentation and example datafiles.

  17. Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma

    Science.gov (United States)

    Shao, Chunbo; Sun, Wenyue; Tan, Marietta; Glazer, Chad A.; Bhan, Sheetal; Zhong, Xiaoli; Fakhry, Carole; Sharma, Rajni; Westra, William H.; Hoque, Mohammad O.; Moskaluk, Christopher A.; Sidransky, David; Califano, Joseph A.; Ha, Patrick K.

    2011-01-01

    Purpose Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy that is poorly understood. In order to look for relevant oncogene candidates under the control of promoter methylation, an integrated, genome-wide screen was performed. Experimental Design Global demethylation of normal salivary gland cell strains using 5-aza-2′-deoxycytidine (5-Aza dC) and Trichostatin A (TSA), followed by expression array analysis was performed. ACC-specific expression profiling was generated using expression microarray analysis of primary ACC and normal samples. Next, the two profiles were integrated to identify a subset of genes for further validation of promoter demethylation in ACC versus normal. Finally, promising candidates were further validated for mRNA, protein, and promoter methylation levels in larger ACC cohorts. Functional validation was then performed in cancer cell lines. Results We found 159 genes that were significantly re-expressed after 5-Aza dC/TSA treatment and overexpressed in ACC. After initial validation, eight candidates showed hypomethylation in ACC: AQP1, CECR1, C1QR1, CTAG2, P53AIP1, TDRD12, BEX1, and DYNLT3. Aquaporin 1 (AQP1) showed the most significant hypomethylation and was further validated. AQP1 hypomethylation in ACC was confirmed with two independent cohorts. Of note, there was significant overexpression of AQP1 in both mRNA and protein in the paraffin-embedded ACC cohort. Furthermore, AQP1 was up-regulated in 5-Aza dC/TSA treated SACC83. Lastly, AQP1 promoted cell proliferation and colony formation in SACC83. Conclusions Our integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC. AQP1 is a promising oncogene candidate for ACC and is transcriptionally regulated by promoter hypomethylation. PMID:21551254

  18. Portal hypertension due to portal venous thrombosis: Etiology, clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ozgur Harmanci; Yusuf Bayraktar

    2007-01-01

    The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting clinical pictures. There are controversial issues in nomenclature,management (including anticoagulation problems), follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.

  19. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

    Directory of Open Access Journals (Sweden)

    Ryan Barnes

    2017-01-01

    Full Text Available Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize “difficult to replicate” genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  20. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases.

    Science.gov (United States)

    Barnes, Ryan; Eckert, Kristin

    2017-01-06

    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize "difficult to replicate" genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  1. Genomic paradigms for food-borne enteric pathogen analysis at the USFDA: case studies highlighting method utility, integration and resolution.

    Science.gov (United States)

    Elkins, C A; Kotewicz, M L; Jackson, S A; Lacher, D W; Abu-Ali, G S; Patel, I R

    2013-01-01

    Modern risk control and food safety practices involving food-borne bacterial pathogens are benefiting from new genomic technologies for rapid, yet highly specific, strain characterisations. Within the United States Food and Drug Administration (USFDA) Center for Food Safety and Applied Nutrition (CFSAN), optical genome mapping and DNA microarray genotyping have been used for several years to quickly assess genomic architecture and gene content, respectively, for outbreak strain subtyping and to enhance retrospective trace-back analyses. The application and relative utility of each method varies with outbreak scenario and the suspect pathogen, with comparative analytical power enhanced by database scale and depth. Integration of these two technologies allows high-resolution scrutiny of the genomic landscapes of enteric food-borne pathogens with notable examples including Shiga toxin-producing Escherichia coli (STEC) and Salmonella enterica serovars from a variety of food commodities. Moreover, the recent application of whole genome sequencing technologies to food-borne pathogen outbreaks and surveillance has enhanced resolution to the single nucleotide scale. This new wealth of sequence data will support more refined next-generation custom microarray designs, targeted re-sequencing and "genomic signature recognition" approaches involving a combination of genes and single nucleotide polymorphism detection to distil strain-specific fingerprinting to a minimised scale. This paper examines the utility of microarrays and optical mapping in analysing outbreaks, reviews best practices and the limits of these technologies for pathogen differentiation, and it considers future integration with whole genome sequencing efforts.

  2. Existence of variant strains Fowlpox virus integrated with Reticuloendotheliosis virus in its genome in field isolates in Tanzania.

    Science.gov (United States)

    Mzula, Alexanda; Masola, Selemani N; Kasanga, Christopher J; Wambura, Philemon N

    2014-06-01

    Fowlpox virus (FPV) is one example of poultry viruses which undergoes recombination with Reticuloendotheliosis virus (REV). Trepidation had been raised, and it was well established on augmented pathogenicity of the FPV upon integration of the full intact REV. In this study, we therefore intended at assessing the integration of REV into FPV genome of the field isolates obtained in samples collected from different regions of Tanzania. DNA extraction of 85 samples (scabs) was performed, and FPV-specific PCR was done by the amplification of the highly conserved P4b gene. Evaluation of FPV-REV recombination was done to FPV-specific PCR positively identified samples by amplifying the env gene and REV long terminal repeats (5' LTR). A 578-bp PCR product was amplified from 43 samples. We are reporting for the first time in Tanzania the existence of variant stains of FPV integrated with REV in its genome as 65 % of FPV identified isolates were having full intact REV integration, 21 % had partial FPV-REV env gene integration and 5 % had partial 5' LTR integration. Despite of the fact that FPV-REV integrated stains prevailed, FPV-REV-free isolates (9 %) also existed. In view of the fact that full intact REV integration is connected with increased pathogenicity of FPV, its existence in the FPV genome of most field isolates could have played a role in increased endemic, sporadic and recurring outbreaks in selected areas in Tanzania.

  3. Structure-Function Analysis of the DNA Translocating Portal of the Bacteriophage T4 Packaging Machine

    Science.gov (United States)

    Padilla-Sanchez, Victor; Gao, Song; Kim, Hyung Rae; Kihara, Daisuke; Sun, Lei; Rossmann, Michael G.; Rao, Venigalla B.

    2013-01-01

    Tailed bacteriophages and herpesviruses consist of a structurally well conserved dodecameric portal at a special five-fold vertex of the capsid. The portal plays critical roles in head assembly, genome packaging, neck/tail attachment, and genome ejection. Although the structures of portals from phages φ29, SPP1 and P22 have been determined, their mechanistic roles have not been well understood. Structural analysis of phage T4 portal (gp20) has been hampered because of its unusual interaction with the E. coli inner membrane. Here, we predict atomic models for the T4 portal monomer and dodecamer, and fit the dodecamer into the cryoEM density of the phage portal vertex. The core structure, like that from other phages, is cone-shaped with the wider end containing the “wing” and “crown” domains inside the phage head. A long “stem” encloses a central channel, and a narrow “stalk” protrudes outside the capsid. A biochemical approach was developed to analyze portal function by incorporating plasmid-expressed portal protein into phage heads and determining the effect of mutations on head assembly, DNA translocation, and virion production. We found that the protruding loops of the stalk domain are involved in assembling the DNA packaging motor. A loop that connects the stalk to the channel might be required for communication between the motor and portal. The “tunnel” loops that project into the channel are essential for sealing the packaged head. These studies established that the portal is required throughout the DNA packaging process, with different domains participating at different stages of genome packaging. PMID:24126213

  4. 国土资源部门户网站整合总体要求%General Requirements of the Ministry of Land and Resources on the Integration of Portal Websites

    Institute of Scientific and Technical Information of China (English)

    顾炳中

    2012-01-01

    The integration of portal sites involves not only the integration of content,but also that of technology platforms;it is much more constant adjustment of the constructing train of thought and innovation.Founded on the principles of integration that is on the unified planning,unified standards,unified platforms,unified management,integration of content and interactive communication with which have been put in place the overall objectives by integrating hardware,software unified,content and form,this paper proposes a basic orientation of the current period that should be promoting the publicity and guidance,work online,collaborative operational activities,and interactive communication.The paper also explains,with reflection on promoting the engineering of security system,in focusing on the goals of integration content and specific content as to the integration of platforms technologies,highlighting the idea of planning the next stage of development of the site.%门户网站整合既是内容的整合也是技术平台的整合,同时更是建设思路的不断调整和创新。本文提出了现阶段以宣传引导、网上办事、业务协同、互动交流为基本定位,以统一规划、统一标准、统一平台、统一管理、内容整合、交流互动为整合原则,以硬件、软件、内容、形式到管理全面统一的整合目标。并分别对内容整合的方向和技术平台整合的具体内容进行了重点阐述。同时对完善管理机制,推进安全保障体系建设进行了思考和分析,并提出了对网站下一步发展规划的设想。

  5. WLCG Operations portal demo tutorial

    CERN Document Server

    CERN. Geneva

    2016-01-01

    This is a navigation through http://wlcg-ops.web.cern.ch/ the Worldwide LHC Computing Grid (WLCG) Operations' portal. In this portal you will find documentation and information about WLCG Operation activities for: System Administrators at the WLCG sites LHC Experiments Operation coordination people, including Task Forces and Working Groups

  6. Portal dosimetry in wedged beams

    NARCIS (Netherlands)

    Spreeuw, H.; Rozendaal, R.; Camargo, P.; Mans, A.; Wendling, M.; Olaciregui-Ruiz, I.; Sonke, J.J.; Herk, M. van; Mijnheer, B.

    2015-01-01

    Portal dosimetry using electronic portal imaging devices (EPIDs) is often applied to verify high-energy photon beam treatments. Due to the change in photon energy spectrum, the resulting dose values are, however, not very accurate in the case of wedged beams if the pixel-to-dose conversion for the s

  7. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...

  8. NSTA Portal to Science Safety

    Science.gov (United States)

    Roy, Ken

    2010-01-01

    The National Science Teachers Association's (NSTA) Science Safety Advisory Board recently launched the Safety in the Science Classroom portal. This portal serves as a gateway to safety resources for teachers, supervisors, and administrators. It also contains an evolving list of safety resources for elementary, middle, and high schools. The list…

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

    Science.gov (United States)

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

    2017-01-25

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

  10. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Science.gov (United States)

    Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T Jake

    2014-05-01

    Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host

  11. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

    Directory of Open Access Journals (Sweden)

    Qisheng Li

    2014-05-01

    Full Text Available Recent functional genomics studies including genome-wide small interfering RNA (siRNA screens demonstrated that hepatitis C virus (HCV exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp, single-cycle infectious particles (HCVsc, subgenomic replicons, and HCV cell culture systems (HCVcc, we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE, a proviral factor, and N-Myc down regulated Gene 1 (NDRG1, an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study

  12. The cost of wobble translation in fungal mitochondrial genomes: integration of two traditional hypotheses

    Directory of Open Access Journals (Sweden)

    Xia Xuhua

    2008-07-01

    Full Text Available Abstract Background Fungal and animal mitochondrial genomes typically have one tRNA for each synonymous codon family. The codon-anticodon adaptation hypothesis predicts that the wobble nucleotide of a tRNA anticodon should evolve towards maximizing Watson-Crick base pairing with the most frequently used codon within each synonymous codon family, whereas the wobble versatility hypothesis argues that the nucleotide at the wobble site should be occupied by a nucleotide most versatile in wobble pairing, i.e., the tRNA wobble nucleotide should be G for NNY codon families, and U for NNR and NNN codon families (where Y stands for C or U, R for A or G and N for any nucleotide. Results We here integrate these two traditional hypotheses on tRNA anticodons into a unified model based on an analysis of the wobble costs associated with different wobble base pairs. This novel approach allows the relative cost of wobble pairing to be qualitatively evaluated. A comprehensive study of 36 fungal genomes suggests very different costs between two kinds of U:G wobble pairs, i.e., (1 between a G at the wobble site of a tRNA anticodon and a U at the third codon position (designated MU3:G and (2 between a U at the wobble site of a tRNA anticodon and a G at the third codon position (designated MG3:U. Conclusion In general, MU3:G is much smaller than MG3:U, suggesting no selection against U-ending codons in NNY codon families with a wobble G in the tRNA anticodon but strong selection against G-ending codons in NNR codon families with a wobble U at the tRNA anticodon. This finding resolves several puzzling observations in fungal genomics and corroborates previous studies showing that U3:G wobble is energetically more favorable than G3:U wobble.

  13. Final Report for DOE Project: Portal Web Services: Support of DOE SciDAC Collaboratories

    Energy Technology Data Exchange (ETDEWEB)

    Mary Thomas, PI; Geoffrey Fox, Co-PI; Gannon, D; Pierce, M; Moore, R; Schissel, D; Boisseau, J

    2007-10-01

    Grid portals provide the scientific community with familiar and simplified interfaces to the Grid and Grid services, and it is important to deploy grid portals onto the SciDAC grids and collaboratories. The goal of this project is the research, development and deployment of interoperable portal and web services that can be used on SciDAC National Collaboratory grids. This project has four primary task areas: development of portal systems; management of data collections; DOE science application integration; and development of web and grid services in support of the above activities.

  14. Pathways for Genome Integrity in G2 Phase of the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Claus Storgaard Sørensen

    2012-11-01

    Full Text Available The maintenance of genome integrity is important for normal cellular functions, organism development and the prevention of diseases, such as cancer. Cellular pathways respond immediately to DNA breaks leading to the initiation of a multi-facetted DNA damage response, which leads to DNA repair and cell cycle arrest. Cell cycle checkpoints provide the cell time to complete replication and repair the DNA damage before it can continue to the next cell cycle phase. The G2/M checkpoint plays an especially important role in ensuring the propagation of error-free copies of the genome to each daughter cell. Here, we review recent progress in our understanding of DNA repair and checkpoint pathways in late S and G2 phases. This review will first describe the current understanding of normal cell cycle progression through G2 phase to mitosis. It will also discuss the DNA damage response including cell cycle checkpoint control and DNA double-strand break repair. Finally, we discuss the emerging concept that DNA repair pathways play a major role in the G2/M checkpoint pathway thereby blocking cell division as long as DNA lesions are present.

  15. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  16. Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing.

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology.

  17. 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/.

  18. Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

  19. Genomic DNA extraction from cells by electroporation on an integrated microfluidic platform.

    Science.gov (United States)

    Geng, Tao; Bao, Ning; Sriranganathanw, Nammalwar; Li, Liwu; Lu, Chang

    2012-11-06

    The vast majority of genetic analysis of cells involves chemical lysis for release of DNA molecules. However, chemical reagents required in the lysis interfere with downstream molecular biology and often require removal after the step. Electrical lysis based on irreversible electroporation is a promising technique to prepare samples for genetic analysis due to its purely physical nature, fast speed, and simple operation. However, there has been no experimental confirmation on whether electrical lysis extracts genomic DNA from cells in a reproducible and efficient fashion in comparison to chemical lysis, especially for eukaryotic cells that have most of the DNA enclosed in the nucleus. In this work, we construct an integrated microfluidic chip that physically traps a low number of cells, lyses the cells using electrical pulses rapidly, then purifies and concentrates genomic DNA. We demonstrate that electrical lysis offers high efficiency for DNA extraction from both eukaryotic cells (up to ∼36% for Chinese hamster ovary cells) and bacterial cells (up to ∼45% for Salmonella typhimurium) that is comparable to the widely used chemical lysis. The DNA extraction efficiency has dependence on both the electric parameters and relative amount of beads used for DNA adsorption. We envision that electroporation-based DNA extraction will find use in ultrasensitive assays that benefit from minimal dilution and simple procedures.

  20. Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.

    Science.gov (United States)

    Borad, Mitesh J; Egan, Jan B; Condjella, Rachel M; Liang, Winnie S; Fonseca, Rafael; Ritacca, Nicole R; McCullough, Ann E; Barrett, Michael T; Hunt, Katherine S; Champion, Mia D; Patel, Maitray D; Young, Scott W; Silva, Alvin C; Ho, Thai H; Halfdanarson, Thorvardur R; McWilliams, Robert R; Lazaridis, Konstantinos N; Ramanathan, Ramesh K; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Cuyugan, Lori; McDonald, Jacquelyn; Adkins, Jonathan; Mastrian, Stephen D; Valdez, Riccardo; Jaroszewski, Dawn E; Von Hoff, Daniel D; Craig, David W; Stewart, A Keith; Carpten, John D; Bryce, Alan H

    2016-12-23

    DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.

  1. Reframed Genome-Scale Metabolic Model to Facilitate Genetic Design and Integration with Expression Data.

    Science.gov (United States)

    Gu, Deqing; Jian, Xingxing; Zhang, Cheng; Hua, Qiang

    2016-06-08

    Genome-scale metabolic network models (GEMs) have played important roles in the design of genetically engineered strains and helped biologists to decipher metabolism. However, due to the complex gene-reaction relationships that exist in model systems, most algorithms have limited capabilities with respect to directly predicting accurate genetic design for metabolic engineering. In particular, methods that predict reaction knockout strategies leading to overproduction are often impractical in terms of gene manipulations. Recently, we proposed a method named LTM (logical transformation of model) to simplify the gene-reaction associations by introducing intermediate pseudo reactions, which makes it possible to generate genetic design. Here, we propose an alternative method to relieve researchers from deciphering complex gene-reactions by adding pseudo gene controlling reactions. In comparison to LTM, this new method introduces fewer pseudo reactions and generates a much smaller model system named as gModel. We showed that gModel allows two seldom reported applications: identification of minimal genomes and design of minimal cell factories within a modified OptKnock framework. In addition, gModel could be used to integrate expression data directly and improve the performance of the E-Fmin method for predicting fluxes. In conclusion, the model transformation procedure will facilitate genetic research based on GEMs, extending their applications.

  2. 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.

  3. 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.

  4. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    Science.gov (United States)

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology.

  5. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    Science.gov (United States)

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.

  6. 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...... polymorphisms (SNPs) and transcript abundances in explaining phenotypic variance, using Bayesian whole-omics models. Bayesian mixed models and variable selection models were used and, based on parameter samples from the model posterior distributions, explained variances were further partitioned at the level......-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...

  7. On the road with WRAP53β: guardian of Cajal bodies and genome integrity

    Directory of Open Access Journals (Sweden)

    Marianne eFarnebo

    2015-03-01

    Full Text Available The WRAP53 gene encodes both an antisense transcript (WRAP53α that stabilizes the tumor suppressor p53 and a protein (WRAP53β involved in maintenance of Cajal bodies, telomere elongation and DNA repair. WRAP53β is one of many proteins containing WD40 domains, known to mediate a variety of cellular processes. These proteins lack enzymatic activity, acting instead as platforms for the assembly of large complexes of proteins and RNAs thus facilitating their interactions. WRAP53β mediates site-specific interactions between Cajal body factors and DNA repair proteins. Moreover, dysfunction of this protein has been linked to telomere shortening, premature aging, carcinogenesis and neurodegeneration. Here we summarize the current state of knowledge concerning the multifaceted roles of WRAP53β in intracellular trafficking, formation of the Cajal body, DNA repair and maintenance of genomic integrity and discuss potential crosstalk between these processes.

  8. On the road with WRAP53β: guardian of Cajal bodies and genome integrity.

    Science.gov (United States)

    Henriksson, Sofia; Farnebo, Marianne

    2015-01-01

    The WRAP53 gene encodes both an antisense transcript (WRAP53α) that stabilizes the tumor suppressor p53 and a protein (WRAP53β) involved in maintenance of Cajal bodies, telomere elongation and DNA repair. WRAP53β is one of many proteins containing WD40 domains, known to mediate a variety of cellular processes. These proteins lack enzymatic activity, acting instead as platforms for the assembly of large complexes of proteins and RNAs thus facilitating their interactions. WRAP53β mediates site-specific interactions between Cajal body factors and DNA repair proteins. Moreover, dysfunction of this protein has been linked to premature aging, cancer and neurodegeneration. Here we summarize the current state of knowledge concerning the multifaceted roles of WRAP53β in intracellular trafficking, formation of the Cajal body, DNA repair and maintenance of genomic integrity and discuss potential crosstalk between these processes.

  9. An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes.

    Directory of Open Access Journals (Sweden)

    Ling Bai

    2016-04-01

    Full Text Available Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.

  10. Expression of Active Subunit of Nitrogenase via Integration into Plant Organelle Genome

    Science.gov (United States)

    Groat, Jeanna; Staub, Jeffrey M.; Stephens, Michael

    2016-01-01

    Nitrogen availability is crucial for crop yield with nitrogen fertilizer accounting for a large percentage of farmers’ expenses. However, an untimely or excessive application of fertilizer can increase risks of negative environmental effects. These factors, along with the environmental and energy costs of synthesizing nitrogen fertilizer, led us to seek out novel biotechnology-driven approaches to supply nitrogen to plants. The strategy we focused on involves transgenic expression of nitrogenase, a bacterial multi-subunit enzyme that can capture atmospheric nitrogen. Here we report expression of the active Fe subunit of nitrogenase via integration into the tobacco plastid genome of bacterial gene sequences modified for expression in plastid. Our study suggests that it will be possible to engineer plants that are able to produce their own nitrogen fertilizer by expressing nitrogenase genes in plant plastids. PMID:27529475

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

    Directory of Open Access Journals (Sweden)

    Farshad Farshidfar

    2017-03-01

    Full Text Available 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 intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  12. DES Science Portal: Computing Photometric Redshifts

    Energy Technology Data Exchange (ETDEWEB)

    Gschwend, Julia [LIneA, Rio de Janeiro

    2016-01-01

    An important challenge facing photometric surveys for cosmological purposes, such as the Dark Energy Survey (DES), is the need to produce reliable photometric redshifts (photo-z). The choice of adequate algorithms and configurations and the maintenance of an up-to-date spectroscopic database to build training sets, for example, are challenging tasks when dealing with large amounts of data that are regularly updated and constantly growing. In this paper, we present the first of a series of tools developed by DES, provided as part of the DES Science Portal, an integrated web-based data portal developed to facilitate the scientific analysis of the data, while ensuring the reproducibility of the analysis. We present the DES Science Portal photometric redshift tools, starting from the creation of a spectroscopic sample to training the neural network photo-z codes, to the final estimation of photo-zs for a large photometric catalog. We illustrate this operation by calculating well calibrated photo-zs for a galaxy sample extracted from the DES first year (Y1A1) data. The series of processes mentioned above is run entirely within the Portal environment, which automatically produces validation metrics, and maintains the provenance between the different steps. This system allows us to fine tune the many steps involved in the process of calculating photo-zs, making sure that we do not lose the information on the configurations and inputs of the previous processes. By matching the DES Y1A1 photometry to a spectroscopic sample, we define different training sets that we use to feed the photo-z algorithms already installed at the Portal. Finally, we validate the results under several conditions, including the case of a sample limited to i<22.5 with the color properties close to the full DES Y1A1 photometric data. This way we compare the performance of multiple methods and training configurations. The infrastructure presented here is an effcient way to test several methods of

  13. 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

  14. 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.

  15. Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity.

    Science.gov (United States)

    Ui, Ayako; Yasui, Akira

    2016-04-25

    Polycomb group (PcG) repress, whereas Trithorax group (TrxG) activate transcription for tissue development and cellular proliferation, and misregulation of these factors is often associated with cancer. ENL (MLLT1) and AF9 (MLLT3) are fusion partners of Mixed Lineage Leukemia (MLL), TrxG proteins, and are factors in Super Elongation Complex (SEC). SEC controls transcriptional elongation to release RNA polymerase II, paused around transcription start site. In MLL rearranged leukemia, several components of SEC have been found as MLL-fusion partners and the control of transcriptional elongation is misregulated leading to tumorigenesis in MLL-SEC fused Leukemia. It has been suggested that unexpected collaboration of ENL/AF9-MLL and PcG are involved in tumorigenesis in leukemia. Recently, we found that the collaboration of ENL/AF9 and PcG led to a novel mechanism of transcriptional switch from elongation to repression under ATM-signaling for genome integrity. Activated ATM phosphorylates ENL/AF9 in SEC, and the phosphorylated ENL/AF9 binds BMI1 and RING1B, a heterodimeric E3-ubiquitin-ligase complex in Polycomb Repressive complex 1 (PRC1), and recruits PRC1 at transcriptional elongation sites to rapidly repress transcription. The ENL/AF9 in SEC- and PcG-mediated transcriptional repression promotes DSB repair near transcription sites. The implication of this is that the collaboration of ENL/AF9 in SEC and PcG ensures a rapid response of transcriptional switching from elongation to repression to neighboring genotoxic stresses for DSB repair. Therefore, these results suggested that the collaboration of ENL/AF9 and PcG in transcriptional control is required to maintain genome integrity and may be link to the MLL-ENL/AF9 leukemia.

  16. DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity.

    Directory of Open Access Journals (Sweden)

    Katherine S Lawrence

    2015-04-01

    Full Text Available Errors in replication or segregation lead to DNA damage, mutations, and aneuploidies. Consequently, cells monitor these events and delay progression through the cell cycle so repair precedes division. The DNA damage response (DDR, which monitors DNA integrity, and the spindle assembly checkpoint (SAC, which responds to defects in spindle attachment/tension during metaphase of mitosis and meiosis, are critical for preventing genome instability. Here we show that the DDR and SAC function together throughout the cell cycle to ensure genome integrity in C. elegans germ cells. Metaphase defects result in enrichment of SAC and DDR components to chromatin, and both SAC and DDR are required for metaphase delays. During persistent metaphase arrest following establishment of bi-oriented chromosomes, stability of the metaphase plate is compromised in the absence of DDR kinases ATR or CHK1 or SAC components, MAD1/MAD2, suggesting SAC functions in metaphase beyond its interactions with APC activator CDC20. In response to DNA damage, MAD2 and the histone variant CENPA become enriched at the nuclear periphery in a DDR-dependent manner. Further, depletion of either MAD1 or CENPA results in loss of peripherally associated damaged DNA. In contrast to a SAC-insensitive CDC20 mutant, germ cells deficient for SAC or CENPA cannot efficiently repair DNA damage, suggesting that SAC mediates DNA repair through CENPA interactions with the nuclear periphery. We also show that replication perturbations result in relocalization of MAD1/MAD2 in human cells, suggesting that the role of SAC in DNA repair is conserved.

  17. HR4EU--A Web-Portal for E-Learning of Croatian

    Science.gov (United States)

    Filko, Matea; Farkaš, Daša; Hriberski, Diana

    2016-01-01

    In this paper, we present the HR4EU--a web portal for e-learning of Croatian. HR4EU is the first portal that offers Croatian language courses which are free-of-charge and developed by language professionals. Moreover, HR4EU also integrates bidirectional interaction with some of the previously developed language resources for Croatian. The HR4EU…

  18. Factors Affecting the Use of an E-Learning Portal at University

    Science.gov (United States)

    Cegarra-Navarro, Juan-Gabriel; Rodriguez, Francisco Javier Canovas

    2012-01-01

    Electronic learning (e-learning) portals can be defined as websites that store and present materials for online learning, training, performance assessment, and certification. Few, if any, studies have investigated the factors that might contribute to the integration or implementation of e-learning portals in universities. With the development of…

  19. Integrated genome-scale analysis of the transcriptional regulatory landscape in a blood stem/progenitor cell model.

    Science.gov (United States)

    Wilson, Nicola K; Schoenfelder, Stefan; Hannah, Rebecca; Sánchez Castillo, Manuel; Schütte, Judith; Ladopoulos, Vasileios; Mitchelmore, Joanna; Goode, Debbie K; Calero-Nieto, Fernando J; Moignard, Victoria; Wilkinson, Adam C; Jimenez-Madrid, Isabel; Kinston, Sarah; Spivakov, Mikhail; Fraser, Peter; Göttgens, Berthold

    2016-03-31

    Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well-recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology. © 2016 by The American Society of Hematology.

  20. The Portuguese Climate Portal

    Science.gov (United States)

    Gomes, Sandra; Deus, Ricardo; Nogueira, Miguel; Viterbo, Pedro; Miranda, Miguel; Antunes, Sílvia; Silva, Alvaro; Miranda, Pedro

    2016-04-01

    The Portuguese Local Warming Website (http://portaldoclima.pt) has been developed in order to support the society in Portugal in preparing for the adaptation to the ongoing and future effects of climate change. The climate portal provides systematic and easy access to authoritative scientific data ready to be used by a vast and diverse user community from different public and private sectors, key players and decision makers, but also to high school students, contributing to the increase in knowledge and awareness on climate change topics. A comprehensive set of regional climate variables and indicators are computed, explained and graphically presented. Variables and indicators were built in agreement with identified needs after consultation of the relevant social partners from different sectors, including agriculture, water resources, health, environment and energy and also in direct cooperation with the Portuguese National Strategy for Climate Change Adaptation (ENAAC) group. The visual interface allows the user to dynamically interact, explore, quickly analyze and compare, but also to download and import the data and graphics. The climate variables and indicators are computed from state-of-the-art regional climate model (RCM) simulations (e.g., CORDEX project), at high space-temporal detail, allowing to push the limits of the projections down to local administrative regions (NUTS3) and monthly or seasonal periods, promoting local adaptation strategies. The portal provides both historical data (observed and modelled for the 1971-2000 period) and future climate projections for different scenarios (modelled for the 2011-2100 period). A large effort was undertaken in order to quantify the impacts of the risk of extreme events, such as heavy rain and flooding, droughts, heat and cold waves, and fires. Furthermore the different climate scenarios and the ensemble of RCM models, with high temporal (daily) and spatial (~11km) detail, is taken advantage in order to

  1. SymbioGenomesDB: a database for the integration and access to knowledge on host-symbiont relationships.

    Science.gov (United States)

    Reyes-Prieto, Mariana; Vargas-Chávez, Carlos; Latorre, Amparo; Moya, Andrés

    2015-01-01

    Symbiotic relationships occur naturally throughout the tree of life, either in a commensal, mutualistic or pathogenic manner. The genomes of multiple organisms involved in symbiosis are rapidly being sequenced and becoming available, especially those from the microbial world. Currently, there are numerous databases that offer information on specific organisms or models, but none offer a global understanding on relationships between organisms, their interactions and capabilities within their niche, as well as their role as part of a system, in this case, their role in symbiosis. We have developed the SymbioGenomesDB as a community database resource for laboratories which intend to investigate and use information on the genetics and the genomics of organisms involved in these relationships. The ultimate goal of SymbioGenomesDB is to host and support the growing and vast symbiotic-host relationship information, to uncover the genetic basis of such associations. SymbioGenomesDB maintains a comprehensive organization of information on genomes of symbionts from diverse hosts throughout the Tree of Life, including their sequences, their metadata and their genomic features. This catalog of relationships was generated using computational tools, custom R scripts and manual integration of data available in public literature. As a highly curated and comprehensive systems database, SymbioGenomesDB provides web access to all the information of symbiotic organisms, their features and links to the central database NCBI. Three different tools can be found within the database to explore symbiosis-related organisms, their genes and their genomes. Also, we offer an orthology search for one or multiple genes in one or multiple organisms within symbiotic relationships, and every table, graph and output file is downloadable and easy to parse for further analysis. The robust SymbioGenomesDB will be constantly updated to cope with all the data being generated and included in major

  2. Patient Portals as a Tool for Health Care Engagement: A Mixed-Method Study of Older Adults With Varying Levels of Health Literacy and Prior Patient Portal Use.

    Science.gov (United States)

    Irizarry, Taya; Shoemake, Jocelyn; Nilsen, Marci Lee; Czaja, Sara; Beach, Scott; DeVito Dabbs, Annette

    2017-03-30

    Growing evidence that patient engagement improves health outcomes and reduces health care costs has fueled health providers' focus on patient portals as the primary access point for personal health information and patient-provider communication. Whereas much attention has been given to identifying characteristics of older adults who do and do not adopt patient portals and necessary adaptions to portal design, little is known about their attitudes and perceptions regarding patient portal use as a tool for engagement in their health care within the context of health literacy, experience navigating Web-based health information, and previous patient portal use. The specific aims of this study were to explore attitudes toward portal adoption and its perceived usefulness as a tool for health care engagement among adults (65 years and older) who have varying levels of health literacy and degrees of prior patient portal use. A phone survey of 100 community dwelling adults gathered sociodemographic, health, and technology related information. Older adults were purposefully selected for 4 follow-up focus groups based on survey responses to health literacy and previous patient portal use. A mixed-method approach was used to integrate phone survey data with thematic analysis of 4 focus groups. Due to variability in attitudes between focus group participants, an individual case analysis was performed and thematic patterns were used as the basis for subgroup formation. Differences in health literacy, comfort navigating health information on the Web, and previous portal experience explained some but not all differences related to the 7 themes that emerged in the focus groups analysis. Individual cases who shared attitudes were arranged into 5 subgroups from least to most able and willing to engage in health care via a patient portal. The subgroups' overall portal adoption attitudes were: (1) Don't want to feel pushed into anything, (2) Will only adopt if required, (3) Somebody

  3. BGD: a database of bat genomes.

    Directory of Open Access Journals (Sweden)

    Jianfei Fang

    Full Text Available Bats account for ~20% of mammalian species, and are the only mammals with true powered flight. For the sake of their specialized phenotypic traits, many researches have been devoted to examine the evolution of bats. Until now, some whole genome sequences of bats have been assembled and annotated, however, a uniform resource for the annotated bat genomes is still unavailable. To make the extensive data associated with the bat genomes accessible to the general biological communities, we established a Bat Genome Database (BGD. BGD is an open-access, web-available portal that integrates available data of bat genomes and genes. It hosts data from six bat species, including two megabats and four microbats. Users can query the gene annotations using efficient searching engine, and it offers browsable tracks of bat genomes. Furthermore, an easy-to-use phylogenetic analysis tool was also provided to facilitate online phylogeny study of genes. To the best of our knowledge, BGD is the first database of bat genomes. It will extend our understanding of the bat evolution and be advantageous to the bat sequences analysis. BGD is freely available at: http://donglab.ecnu.edu.cn/databases/BatGenome/.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-03

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

  5. 29 CFR 785.34 - Effect of section 4 of the Portal-to-Portal Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Effect of section 4 of the Portal-to-Portal Act. 785.34 Section 785.34 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR... of Principles Traveltime § 785.34 Effect of section 4 of the Portal-to-Portal Act. The Portal...

  6. Integrative radiogenomic analysis for genomic signatures in glioblastomas presenting leptomeningeal dissemination.

    Science.gov (United States)

    You, Hye Jin; Park, Ho-Young; Kim, Jinkuk; Lee, In-Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Sung Tae; Kong, Doo-Sik; Nam, Do-Hyun

    2016-07-01

    Despite therapeutic advances, the prognosis for glioblastoma (GBM) remains poor. In particular, leptomeningeal dissemination (LMD) has a dismal prognosis. The aim of this study was to identify tumor molecular phenotype, which has a great propensity to develop LMD. Between May 2004 and December 2012, a total of 145 GBM tumor samples were obtained from data registry. A total of 20 of the 145 patients with GBM were found to develop LMD. A specialized radiologist confirmed the diagnosis of LMD on magnetic resonance imaging. To clarify the genomic signatures in GBM with LMD, we performed integrative analysis of whole transcriptome sequencing and copy number alteration in the radiological features indicating LMD phenotypes in GBM. Eleven newly diagnosed patients with GBM with LMD had worse prognosis than those without LMD (median 5.55 vs. 12.94 months, P LMD group. In addition, it was demonstrated that NME2, TMEM100, and SIVA1 were downregulated with the loss of copy number. We also found that mesenchymal subtype accounted for 50% in LMD group, whereas mesenchymal subtype consisted of 29% in non-LMD group, even though there was no statistical significance (P = 0.06). Through this radiogenomic analysis, we suggested the possibility of finding candidate genes associated with LMD and highlighted the significance of integrating approach to clarify the molecular characteristics in LMD.

  7. Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.

    Directory of Open Access Journals (Sweden)

    Ji Hoon Park

    Full Text Available 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.

  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. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    Science.gov (United States)

    Suzuki, Keiichiro; Tsunekawa, Yuji; Hernandez-Benitez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua

    2017-01-01

    Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3,4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies. PMID:27851729

  10. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    KAUST Repository

    Suzuki, Keiichiro

    2016-11-15

    Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

  11. Revisiting the identification of canonical splice isoforms through integration of functional genomics and proteomics evidence.

    Science.gov (United States)

    Li, Hong-Dong; Menon, Rajasree; Omenn, Gilbert S; Guan, Yuanfang

    2014-12-01

    Canonical isoforms in different databases have been defined as the most prevalent, most conserved, most expressed, longest, or the one with the clearest description of domains or posttranslational modifications. In this article, we revisit these definitions of canonical isoforms based on functional genomics and proteomics evidence, focusing on mouse data. We report a novel functional relationship network-based approach for identifying the highest connected isoforms (HCIs). We show that 46% of these HCIs are not the longest transcripts. In addition, this approach revealed many genes that have more than one highly connected isoforms. Averaged across 175 RNA-seq datasets covering diverse tissues and conditions, 65% of the HCIs show higher expression levels than nonhighest connected isoforms at the transcript level. At the protein level, these HCIs highly overlap with the expressed splice variants, based on proteomic data from eight different normal tissues. These results suggest that a more confident definition of canonical isoforms can be made through integration of multiple lines of evidence, including HCIs defined by biological processes and pathways, expression prevalence at the transcript level, and relative or absolute abundance at the protein level. This integrative proteogenomics approach can successfully identify principal isoforms that are responsible for the canonical functions of genes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Integration of Multiple Genomic Data Sources in a Bayesian Cox Model for Variable Selection and Prediction.

    Science.gov (United States)

    Treppmann, Tabea; Ickstadt, Katja; Zucknick, Manuela

    2017-01-01

    Bayesian variable selection becomes more and more important in statistical analyses, in particular when performing variable selection in high dimensions. For survival time models and in the presence of genomic data, the state of the art is still quite unexploited. One of the more recent approaches suggests a Bayesian semiparametric proportional hazards model for right censored time-to-event data. We extend this model to directly include variable selection, based on a stochastic search procedure within a Markov chain Monte Carlo sampler for inference. This equips us with an intuitive and flexible approach and provides a way for integrating additional data sources and further extensions. We make use of the possibility of implementing parallel tempering to help improve the mixing of the Markov chains. In our examples, we use this Bayesian approach to integrate copy number variation data into a gene-expression-based survival prediction model. This is achieved by formulating an informed prior based on copy number variation. We perform a simulation study to investigate the model's behavior and prediction performance in different situations before applying it to a dataset of glioblastoma patients and evaluating the biological relevance of the findings.

  13. 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.

  14. Integration of least angle regression with empirical Bayes for multi-locus genome-wide association studies

    Science.gov (United States)

    Multi-locus genome-wide association studies has become the state-of-the-art procedure to identify quantitative trait loci (QTL) associated with traits simultaneously. However, implementation of multi-locus model is still difficult. In this study, we integrated least angle regression with empirical B...

  15. A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

    NARCIS (Netherlands)

    Pontier, D.B.; Tijsterman, M.

    2009-01-01

    To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ) o

  16. Multi-omic data integration and analysis using systems genomics approaches: methods and applications in animal production, health and welfare.

    Science.gov (United States)

    Suravajhala, Prashanth; Kogelman, Lisette J A; Kadarmideen, Haja N

    2016-04-29

    In the past years, there has been a remarkable development of high-throughput omics (HTO) technologies such as genomics, epigenomics, transcriptomics, proteomics and metabolomics across all facets of biology. This has spearheaded the progress of the systems biology era, including applications on animal production and health traits. However, notwithstanding these new HTO technologies, there remains an emerging challenge in data analysis. On the one hand, different HTO technologies judged on their own merit are appropriate for the identification of disease-causing genes, biomarkers for prevention and drug targets for the treatment of diseases and for individualized genomic predictions of performance or disease risks. On the other hand, integration of multi-omic data and joint modelling and analyses are very powerful and accurate to understand the systems biology of healthy and sustainable production of animals. We present an overview of current and emerging HTO technologies each with a focus on their applications in animal and veterinary sciences before introducing an integrative systems genomics framework for analysing and integrating multi-omic data towards improved animal production, health and welfare. We conclude that there are big challenges in multi-omic data integration, modelling and systems-level analyses, particularly with the fast emerging HTO technologies. We highlight existing and emerging systems genomics approaches and discuss how they contribute to our understanding of the biology of complex traits or diseases and holistic improvement of production performance, disease resistance and welfare.

  17. A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

    NARCIS (Netherlands)

    Pontier, D.B.; Tijsterman, M.

    2009-01-01

    To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ)

  18. Conjugative transfer and cis-mobilization of a genomic island by an integrative and conjugative element of Streptococcus agalactiae.

    Science.gov (United States)

    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie

    2013-03-01

    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913-6917, 2008). We investigated here the mobility of the elements integrated into the 3' end of a tRNA(Lys) gene. Three of the four putative ICEs tested were found to excise but only one (ICE_515_tRNA(Lys)) was found to transfer by conjugation not only to S. agalactiae strains but also to a Streptococcus pyogenes strain. Transfer was observed even if recipient cell already carries a related resident ICE or a genomic island flanked by attL and attR recombination sites but devoid of conjugation or recombination genes (CIs-Mobilizable Element [CIME]). The incoming ICE preferentially integrates into the 3' end of the tRNA(Lys) gene (i.e., the attR site of the resident element), leading to a CIME-ICE structure. Transfer of the whole composite element CIME-ICE was obtained, showing that the CIME is mobilizable in cis by the ICE. Therefore, genomic islands carrying putative virulence genes but lacking the mobility gene can be mobilized by a related ICE after site-specific accretion.

  19. Ricebase: a breeding and genetics platform for rice, integrating individual molecular markers, pedigrees, and whole-genome-based data

    Science.gov (United States)

    Ricebase (http://ricebase.org) is an integrative genomic database for rice (Oryza sativa) with an emphasis on combining data sets in a way that maintains the key links between past and current genetic studies. Ricebase includes DNA sequence data, gene annotations, nucleotide variation data, and mol...

  20. Integration of the cytogenetic, genetic, and physical maps of the human genome by FISH mapping of CEPH YAC clones

    Energy Technology Data Exchange (ETDEWEB)

    Bray-Ward, P.; Menninger, J.; Lieman, J. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1996-02-15

    This article discusses the genetic mapping of over 950 yeast artificial chromosome (YAC) clones on human chromosomes. This integration of the cytogenetic, genetic and physical maps of the human genome was accomplished using fluorescence in situ hybridization (FISH) mapping and the CEPH library of YAC clones. 27 refs., 2 figs., 1 tab.

  1. 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.

  2. The Higgs Portal and Cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Assamagan, Ketevi [Brookhaven National Lab. (BNL), Upton, NY (United States); Chen, Chien-Yi [Perimeter Inst. for Theoretical Physics, Waterloo, ON (Canada); Univ. of Victoria, BC (Canada); Chou, John Paul [Rutgers Univ., Piscataway, NJ (United States); Curtin, David [Univ. of Maryland, College Park, MD (United States); Fedderke, Michael A. [Univ. of Chicago, IL (United States); Gershtein, Yuri [Rutgers Univ., Piscataway, NJ (United States); He, Xiao-Gang [Shanghai Jiao Tong Univ. (China); Klute, Markus [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Kozaczuk, Jonathon [TRIUMF, Vancouver, BC (Canada); Kotwal, Ashutosh [Duke Univ., Durham, NC (United States); Lowette, Steven [Vrije Univ., Brussels (Belgium); No, Jose Miguel [Univ. of Sussex, Brighton (United Kingdom); Plehn, Tilman [Heidelberg Univ. (Germany); Qian, Jianming [Univ. of Michigan, Ann Arbor, MI (United States); Ramsey-Musolf, Michael [Univ. of Massachusetts, Amherst, MA (United States); Safonov, Alexei [Texas A & M Univ., College Station, TX (United States); Shelton, Jessie [Univ. of Illinois, Urbana-Champaign, IL (United States); Spannowsky, Michael [Durham Univ. (United Kingdom); Su, Shufang [Univ. of Arizona, Tucson, AZ (United States); Walker, Devin G. E. [Univ. of Washington, Seattle, WA (United States); Willocq, Stephane [Univ. of Massachusetts, Amherst, MA (United States); Winslow, Peter [Univ. of Massachusetts, Amherst, MA (United States)

    2016-04-18

    Higgs portal interactions provide a simple mechanism for addressing two open problems in cosmology: dark matter and the baryon asymmetry. In the latter instance, Higgs portal interactions may contain the ingredients for a strong first-order electroweak phase transition as well as new CP-violating interactions as needed for electroweak baryogenesis. These interactions may also allow for a viable dark matter candidate. We survey the opportunities for probing the Higgs portal as it relates to these questions in cosmology at the LHC and possible future colliders.

  3. Information Portal Costs and Benefits

    Directory of Open Access Journals (Sweden)

    Lorena BATAGAN

    2006-01-01

    Full Text Available All transformations of our society are the product of the large use of Information and Communications Technologies (ICT and Internet. ICT are technologies which facilitate communication, processing, and transmission of information by electronic means. It is very important to use the new technologies to the correct value because this determinate an increase of global benefits. Portal provides a consistent way to select, evaluate, prioritize and plan the right information. In research we point the important costs and benefits for an informational portal. The portal for local administrative determinate for citizens the access to information of interest and on the other hand make easier for employer to manage the documents.

  4. Educational portals: Classification and components

    Directory of Open Access Journals (Sweden)

    Rosana López Carreño

    2008-02-01

    Full Text Available The progressive running of different educational portals needs one definition and classification for its identification, as well as, one enumeration of their usual elements to be able to set up one model of educational portal. This paper revises the main institutional of education portals of the Regional Governments to set up the level of development and to know their possible trends. Furthermore, it no-tices about the importance in the some added value services implementation for the support and the improvement of the educational tasks, as blogs, wikis and webquests

  5. The Higgs Portal and Cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Assamagan, Ketevi [Brookhaven National Lab. (BNL), Upton, NY (United States); Chen, Chien-Yi [Perimeter Inst. for Theoretical Physics, Waterloo, ON (Canada); Univ. of Victoria, BC (Canada); Chou, John Paul [Rutgers Univ., Piscataway, NJ (United States); Curtin, David [Univ. of Maryland, College Park, MD (United States); Fedderke, Michael A. [Univ. of Chicago, IL (United States); Gershtein, Yuri [Rutgers Univ., Piscataway, NJ (United States); He, Xiao-Gang [Shanghai Jiao Tong Univ. (China); Klute, Markus [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Kozaczuk, Jonathon [TRIUMF, Vancouver, BC (Canada); Kotwal, Ashutosh [Duke Univ., Durham, NC (United States); Lowette, Steven [Vrije Univ., Brussels (Belgium); No, Jose Miguel [Univ. of Sussex, Brighton (United Kingdom); Plehn, Tilman [Heidelberg Univ. (Germany); Qian, Jianming [Univ. of Michigan, Ann Arbor, MI (United States); Ramsey-Musolf, Michael [Univ. of Massachusetts, Amherst, MA (United States); Safonov, Alexei [Texas A & M Univ., College Station, TX (United States); Shelton, Jessie [Univ. of Illinois, Urbana-Champaign, IL (United States); Spannowsky, Michael [Durham Univ. (United Kingdom); Su, Shufang [Univ. of Arizona, Tucson, AZ (United States); Walker, Devin G. E. [Univ. of Washington, Seattle, WA (United States); Willocq, Stephane [Univ. of Massachusetts, Amherst, MA (United States); Winslow, Peter [Univ. of Massachusetts, Amherst, MA (United States)

    2016-04-18

    Higgs portal interactions provide a simple mechanism for addressing two open problems in cosmology: dark matter and the baryon asymmetry. In the latter instance, Higgs portal interactions may contain the ingredients for a strong first order electroweak phase transition as well as new CP-violating interactions as needed for electroweak baryogenesis. These interactions may also allow for a viable dark matter candidate. We survey the opportunities for probing the Higgs portal as it relates to these questions in cosmology at the LHC and possible future colliders.

  6. The Higgs Portal and Cosmology

    CERN Document Server

    Assamagan, Ketevi; Chou, John Paul; Curtin, David; Fedderke, Michael A; Gershtein, Yuri; He, Xiao-Gang; Klute, Markus; Kozaczuk, Jonathan; Kotwal, Ashutosh; Lowette, Steven; No, Jose Miguel; Plehn, Tilman; Qian, Jianming; Ramsey-Musolf, Michael; Safonov, Alexei; Shelton, Jessie; Spannowsky, Michael; Su, Shufang; Walker, Devin G E; Willocq, Stephane; Winslow, Peter

    2016-01-01

    Higgs portal interactions provide a simple mechanism for addressing two open problems in cosmology: dark matter and the baryon asymmetry. In the latter instance, Higgs portal interactions may contain the ingredients for a strong first order electroweak phase transition as well as new CP-violating interactions as needed for electroweak baryogenesis. These interactions may also allow for a viable dark matter candidate. We survey the opportunities for probing the Higgs portal as it relates to these questions in cosmology at the LHC and possible future colliders.

  7. Integrative radiogenomic analysis for genomic signatures in glioblastomas presenting leptomeningeal dissemination

    Science.gov (United States)

    You, Hye Jin; Park, Ho-Young; Kim, Jinkuk; Lee, In-Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Sung Tae; Kong, Doo-Sik; Nam, Do-Hyun

    2016-01-01

    Abstract Despite therapeutic advances, the prognosis for glioblastoma (GBM) remains poor. In particular, leptomeningeal dissemination (LMD) has a dismal prognosis. The aim of this study was to identify tumor molecular phenotype, which has a great propensity to develop LMD. Between May 2004 and December 2012, a total of 145 GBM tumor samples were obtained from data registry. A total of 20 of the 145 patients with GBM were found to develop LMD. A specialized radiologist confirmed the diagnosis of LMD on magnetic resonance imaging. To clarify the genomic signatures in GBM with LMD, we performed integrative analysis of whole transcriptome sequencing and copy number alteration in the radiological features indicating LMD phenotypes in GBM. Eleven newly diagnosed patients with GBM with LMD had worse prognosis than those without LMD (median 5.55 vs. 12.94 months, P < 0.0001). Integrating analysis using gene expression based on the change of copy number revealed that SPOCK1, EHD2, SLC2A3, and ANXA11 were highly expressed with the gain of copy number, compared with the gene expression in the non-LMD group. In addition, it was demonstrated that NME2, TMEM100, and SIVA1 were downregulated with the loss of copy number. We also found that mesenchymal subtype accounted for 50% in LMD group, whereas mesenchymal subtype consisted of 29% in non-LMD group, even though there was no statistical significance (P = 0.06). Through this radiogenomic analysis, we suggested the possibility of finding candidate genes associated with LMD and highlighted the significance of integrating approach to clarify the molecular characteristics in LMD. PMID:27399113

  8. Analysis of Streptococcus agalactiae pan-genome for prevalence, diversity and functionality of integrative and conjugative or mobilizable elements integrated in the tRNA(Lys CTT) gene.

    Science.gov (United States)

    Puymège, Aurore; Bertin, Stéphane; Guédon, Gérard; Payot, Sophie

    2015-10-01

    Streptococcus agalactiae is the first cause of invasive infections in human neonates and is also a major bovine and fish pathogen. High genomic diversity was observed in this species that hosts numerous mobile genetic elements, in particular elements transferable by conjugation. This works aims to evaluate the contribution of these elements to GBS genome diversity. Focusing on genomic islands integrated in the tRNA(Lys) (CTT) gene, a known hotspot of recombination, an extensive in silico search was performed on the sequenced genome of 303 strains of S. agalactiae isolated from different hosts. In all the isolates (except 9), whatever their origin (human, bovine, camel, dog, gray seal, dolphin, fish species or bullfrog), this locus carries highly diverse genomic islands transferable by conjugation such as integrative and conjugative elements (ICEs), integrative and mobilizable elements (IMEs), CIs-mobilizable elements (CIMEs) or composite elements. Transfer of an ICE from an ST67 bovine strain to a phylogenetically distant ST23 human isolate was obtained experimentally indicating that there was no barrier to ICE transfer between strains from different hosts. Interestingly, a novel family of putative IMEs that site-specifically integrate in the nic site of oriT of ICEs belonging to Tn916/ICESt3 superfamily was detected in silico. These elements carry an antibiotic resistance gene (lsa(C)) already described to confer cross-resistance to lincosamides, streptogramins A and pleuromutilins. Further work is needed to evaluate the impact of these IMEs on the transfer of targeted ICEs and the mobility and the dissemination of these IMEs.

  9. 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.

  10. Ozone (Environmental Health Student Portal)

    Science.gov (United States)

    Skip Navigation National Library of Medicine Environmental Health Student Portal Connecting Middle School Students to Environmental Health Information Menu Home Air Pollution Air Pollution Home Indoor Air Pollution Outdoor Air ...

  11. Plastics (Environmental Health Student Portal)

    Science.gov (United States)

    Skip Navigation National Library of Medicine Environmental Health Student Portal Connecting Middle School Students to Environmental Health Information Menu Home Air Pollution Air Pollution Home Indoor Air Pollution Outdoor Air ...

  12. Lead (Environmental Health Student Portal)

    Science.gov (United States)

    Skip Navigation National Library of Medicine Environmental Health Student Portal Connecting Middle School Students to Environmental Health Information Menu Home Air Pollution Air Pollution Home Indoor Air Pollution Outdoor Air ...

  13. Arsenic (Environmental Health Student Portal)

    Science.gov (United States)

    Skip Navigation National Library of Medicine Environmental Health Student Portal Connecting Middle School Students to Environmental Health Information Menu Home Air Pollution Air Pollution Home Indoor Air Pollution Outdoor Air ...

  14. Wireless Sensor Portal Technology Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Mobitrum Corporation has demonstrated the feasibility in the Phase I of " A Wireless Sensor Portal Technology" and proposes a Phase II effort to develop a wireless...

  15. IMGMD: A platform for the integration and standardisation of In silico Microbial Genome-scale Metabolic Models.

    Science.gov (United States)

    Ye, Chao; Xu, Nan; Dong, Chuan; Ye, Yuannong; Zou, Xuan; Chen, Xiulai; Guo, Fengbiao; Liu, Liming

    2017-04-07

    Genome-scale metabolic models (GSMMs) constitute a platform that combines genome sequences and detailed biochemical information to quantify microbial physiology at the system level. To improve the unity, integrity, correctness, and format of data in published GSMMs, a consensus IMGMD database was built in the LAMP (Linux + Apache + MySQL + PHP) system by integrating and standardizing 328 GSMMs constructed for 139 microorganisms. The IMGMD database can help microbial researchers download manually curated GSMMs, rapidly reconstruct standard GSMMs, design pathways, and identify metabolic targets for strategies on strain improvement. Moreover, the IMGMD database facilitates the integration of wet-lab and in silico data to gain an additional insight into microbial physiology. The IMGMD database is freely available, without any registration requirements, at http://imgmd.jiangnan.edu.cn/database.

  16. Accelerating discovery for complex neurological and behavioral disorders through systems genetics and integrative genomics in the laboratory mouse.

    Science.gov (United States)

    Bubier, Jason A; Chesler, Elissa J

    2012-04-01

    Recent advances in systems genetics and integrative functional genomics have greatly improved the study of complex neurological and behavioral traits. The methods developed for the integrated characterization of new, high-resolution mouse genetic reference populations and systems genetics enable behavioral geneticists an unprecedented opportunity to address questions of the molecular basis of neurological and psychiatric disorders and their comorbidities. Integrative genomics augment these strategies by enabling rapid informatics-assisted candidate gene prioritization, cross-species translation, and mechanistic comparison across related disorders from a wealth of existing data in mouse and other model organisms. Ultimately, through these complementary approaches, finding the mechanisms and sources of genetic variation underlying complex neurobehavioral disease related traits is becoming tractable. Furthermore, these methods enable categorization of neurobehavioral disorders through their underlying biological basis. Together, these model organism-based approaches can lead to a refinement of diagnostic categories and targeted treatment of neurological and psychiatric disease.

  17. Gaiaverse: the Gaia's outreach portal

    Science.gov (United States)

    Masana, E.

    2017-03-01

    Gaiaverse (http://gaiaverse.eu) is a dissemination portal on the ESA Gaia's mission developed within the GENIUS project, an European project funded by the European Commission to boost the impact of the next European breakthrough in astrophysics, the Gaia astrometric mission. The portal was opened in July 2015. Gaiaverse is administrated by the Universitat de Barcelona (UB) and the Consorci de Serveis Universitaris de Catalunya (CSUC).

  18. The role of the liver histological and necroinflammatory activity in the development of portal hypertension syndrome

    Directory of Open Access Journals (Sweden)

    Dzyubanovsky I.Ya.

    2013-01-01

    Full Text Available Background. Liver cirrhosis is the most often cause of the portal hypertension syndrome development, though structural and morphological liver remodeling usually begins on the stage of chronic hepatitis. Morphologic patterns of the development of portal hypertension syndrome on the pre-clinical stage are still poorly investigated. Objective. To determine the histological and necroinflammatory activity of the liver in patients with portal hypertension. Methods. Patients were divided into four groups: I group (n=38 – chronic hepatitis without clinical signs of portal hypertension; II group (n=42 - chronic hepatitis transforming to cirrhosis with clinical signs of portal hypertension (varicose veins of the esophagus and/or the cardia, splenomegaly, ascitis; III group (n=34 – complicated portal hypertension on the background of liver cirrhosis (bleeding from the varices of the esophagus and/or the cardia, hypersplenism; control group (n=30 - physically healthy individuals aged 23-37 years. An integrated evaluation of the liver histological and necroinflammatory activity through the set of laboratory tests was performed (the method of “FibroTest-ActiTest”; immunofermental analysis of L-FABP concentration. Results. It is found that the patients with pre-clinical stage of portal hypertension syndrome show portal and periportal fibrosis with single septa, and the patients with clinical stages of portal hypertension show portal and periportal cirrhosis with multiple septa. Patients with the complications of portal hypertension show cirrhosis of the liver. With the increase of the necroinflammatory activity the portal pressure increases directly. This fact was confirmed with the increase of L-FABP protein level in the plasma, along with the increase of the actitest results. Conclusion. The diagnostic methodic of “FibroTest-ActiTest” and the plasma level of L-FABP are the modern models for chronic liver disease histological and

  19. INTEGRATING GENOMICS AND PHYLOGENETICS IN UNDERSTANDING THE HISTORY OF TRICHINELLA SPECIES

    Science.gov (United States)

    In 2004, funding was received by Washington University’s Genome Sequencing Center through NHGRI, to completely sequence several nematode genomes as part of a holistic effort to advance our understanding of the human genome and evolution within the Metazoa. Trichinella spiralis was among this group o...

  20. High-throughput genomic mapping of vector integration sites in gene therapy studies.

    Science.gov (United States)

    Beard, Brian C; Adair, Jennifer E; Trobridge, Grant D; Kiem, Hans-Peter

    2014-01-01

    Gene therapy has enormous potential to treat a variety of infectious and genetic diseases. To date hundreds of patients worldwide have received hematopoietic cell products that have been gene-modified with retrovirus vectors carrying therapeutic transgenes, and many patients have been cured or demonstrated disease stabilization as a result (Adair et al., Sci Transl Med 4:133ra57, 2012; Biffi et al., Science 341:1233158, 2013; Aiuti et al., Science 341:1233151, 2013; Fischer et al., Gene 525:170-173, 2013). Unfortunately, for some patients the provirus integration dysregulated the expression of nearby genes leading to clonal outgrowth and, in some cases, cancer. Thus, the unwanted side effect of insertional mutagenesis has become a major concern for retrovirus gene therapy. The careful study of retrovirus integration sites (RIS) and the contribution of individual gene-modified clones to hematopoietic repopulating cells is of crucial importance for all gene therapy studies. Supporting this, the US Food and Drug Administration (FDA) has mandated the careful monitoring of RIS in all clinical trials of gene therapy. An invaluable method was developed: linear amplification mediated-polymerase chain reaction (LAM-PCR) capable of analyzing in vitro and complex in vivo samples, capturing valuable genomic information directly flanking the site of provirus integration. Linking this method and similar methods to high-throughput sequencing has now made possible an unprecedented understanding of the integration profile of various retrovirus vectors, and allows for sensitive monitoring of their safety. It also allows for a detailed comparison of improved safety-enhanced gene therapy vectors. An important readout of safety is the relative contribution of individual gene-modified repopulating clones. One limitation of LAM-PCR is that the ability to capture the relative contribution of individual clones is compromised because of the initial linear PCR common to all current methods

  1. IOOS Data Portals and Uniform On-line Browse Capabilities

    Science.gov (United States)

    Howard, M.; Currier, R. D.; Kobara, S.; Gayanilo, F.

    2015-12-01

    The Gulf of Mexico Coastal Ocean Observing System Regional Association (GCOOS-RA) is one of eleven Regional Associations organized under the NOAA-led U.S. Integrated Ocean Observing System (IOOS) Program Office. Each of the RAs operate standards-based regional data portals designed to aggregate near real-time and historical observed data and modeled outputs from distributed providers and to offer these and derived products in standardized ways to a diverse set of users. The RA's portals are based on the IOOS Data and Communications Plan which describes the functional elements needed for an interoperable system. One of these elements is called "Uniform On-line Browse" which is an informational service designed primarily to visualize the inventory of a portal. An on-line browse service supports the end user's need to discover what parameters are available, to learn the spatial and temporal extend of the holdings, and to examine the character of the data (e.g, variability, gappiness, etc). These pieces of information help the end user decide if the data are fit for his/her purpose and to construct valid data requests. Note that on-line browse is a distinctly different activity than data analysis because it seeks to yield knowledge about the inventory and not about what the data mean. "Uniform" on-line browse is a service that takes advantage of the standardization of the data portal's data access points. Most portals represent station locations on a map. This is a view of the data inventory but these plots are rarely generated by pulling data through the standards-based services offered to the end users but through methods only available to the portal programmers. This work will present results of Uniform On-line browse tools developed within GCOOS-RA and their applicability to other RA portals.

  2. InSilico DB genomic datasets hub: an efficient starting point for analyzing genome-wide studies in GenePattern, Integrative Genomics Viewer, and R/Bioconductor.

    Science.gov (United States)

    Coletta, Alain; Molter, Colin; Duqué, Robin; Steenhoff, David; Taminau, Jonatan; de Schaetzen, Virginie; Meganck, Stijn; Lazar, Cosmin; Venet, David; Detours, Vincent; Nowé, Ann; Bersini, Hugues; Weiss Solís, David Y

    2012-11-18

    Genomics datasets are increasingly useful for gaining biomedical insights, with adoption in the clinic underway. However, multiple hurdles related to data management stand in the way of their efficient large-scale utilization. The solution proposed is a web-based data storage hub. Having clear focus, flexibility and adaptability, InSilico DB seamlessly connects genomics dataset repositories to state-of-the-art and free GUI and command-line data analysis tools. The InSilico DB platform is a powerful collaborative environment, with advanced capabilities for biocuration, dataset sharing, and dataset subsetting and combination. InSilico DB is available from https://insilicodb.org.

  3. Automated integration of genomic physical mapping data via parallel simulated annealing

    Energy Technology Data Exchange (ETDEWEB)

    Slezak, T.

    1994-06-01

    The Human Genome Center at the Lawrence Livermore National Laboratory (LLNL) is nearing closure on a high-resolution physical map of human chromosome 19. We have build automated tools to assemble 15,000 fingerprinted cosmid clones into 800 contigs with minimal spanning paths identified. These islands are being ordered, oriented, and spanned by a variety of other techniques including: Fluorescence Insitu Hybridization (FISH) at 3 levels of resolution, ECO restriction fragment mapping across all contigs, and a multitude of different hybridization and PCR techniques to link cosmid, YAC, AC, PAC, and Pl clones. The FISH data provide us with partial order and distance data as well as orientation. We made the observation that map builders need a much rougher presentation of data than do map readers; the former wish to see raw data since these can expose errors or interesting biology. We further noted that by ignoring our length and distance data we could simplify our problem into one that could be readily attacked with optimization techniques. The data integration problem could then be seen as an M x N ordering of our N cosmid clones which ``intersect`` M larger objects by defining ``intersection`` to mean either contig/map membership or hybridization results. Clearly, the goal of making an integrated map is now to rearrange the N cosmid clone ``columns`` such that the number of gaps on the object ``rows`` are minimized. Our FISH partially-ordered cosmid clones provide us with a set of constraints that cannot be violated by the rearrangement process. We solved the optimization problem via simulated annealing performed on a network of 40+ Unix machines in parallel, using a server/client model built on explicit socket calls. For current maps we can create a map in about 4 hours on the parallel net versus 4+ days on a single workstation. Our biologists are now using this software on a daily basis to guide their efforts toward final closure.

  4. Super DNAging-New insights into DNA integrity, genome stability and telomeres in the oldest old.

    Science.gov (United States)

    Franzke, Bernhard; Neubauer, Oliver; Wagner, Karl-Heinz

    2015-01-01

    Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to "averagely" aged humans. These inverse observations in nonagenarians (90-99 years), centenarians (100-109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in "super old" humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in "successful agers". There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching "super old" age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere

  5. 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.

  6. pico-PLAZA, a genome database of microbial photosynthetic eukaryotes.

    Science.gov (United States)

    Vandepoele, Klaas; Van Bel, Michiel; Richard, Guilhem; Van Landeghem, Sofie; Verhelst, Bram; Moreau, Hervé; Van de Peer, Yves; Grimsley, Nigel; Piganeau, Gwenael

    2013-08-01

    With the advent of next generation genome sequencing, the number of sequenced algal genomes and transcriptomes is rapidly growing. Although a few genome portals exist to browse individual genome sequences, exploring complete genome information from multiple species for the analysis of user-defined sequences or gene lists remains a major challenge. pico-PLAZA is a web-based resource (http://bioinformatics.psb.ugent.be/pico-plaza/) for algal genomics that combines different data types with intuitive tools to explore genomic diversity, perform integrative evolutionary sequence analysis and study gene functions. Apart from homologous gene families, multiple sequence alignments, phylogenetic trees, Gene Ontology, InterPro and text-mining functional annotations, different interactive viewers are available to study genome organization using gene collinearity and synteny information. Different search functions, documentation pages, export functions and an extensive glossary are available to guide non-expert scientists. To illustrate the versatility of the platform, different case studies are presented demonstrating how pico-PLAZA can be used to functionally characterize large-scale EST/RNA-Seq data sets and to perform environmental genomics. Functional enrichments analysis of 16 Phaeodactylum tricornutum transcriptome libraries offers a molecular view on diatom adaptation to different environments of ecological relevance. Furthermore, we show how complementary genomic data sources can easily be combined to identify marker genes to study the diversity and distribution of algal species, for example in metagenomes, or to quantify intraspecific diversity from environmental strains.

  7. NOAA's nowCOAST Web Mapping Portal to Near-Real-Time Coastal Information

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA nowCOAST is a Geographic Information System (GIS)-based Web mapping portal which provides users with an integrated, one-stop access to online, real-time coastal...

  8. DNA replication and spindle checkpoints cooperate during S phase to delay mitosis and preserve genome integrity.

    Science.gov (United States)

    Magiera, Maria M; Gueydon, Elisabeth; Schwob, Etienne

    2014-01-20

    Deoxyribonucleic acid (DNA) replication and chromosome segregation must occur in ordered sequence to maintain genome integrity during cell proliferation. Checkpoint mechanisms delay mitosis when DNA is damaged or upon replication stress, but little is known on the coupling of S and M phases in unperturbed conditions. To address this issue, we postponed replication onset in budding yeast so that DNA synthesis is still underway when cells should enter mitosis. This delayed mitotic entry and progression by transient activation of the S phase, G2/M, and spindle assembly checkpoints. Disabling both Mec1/ATR- and Mad2-dependent controls caused lethality in cells with deferred S phase, accompanied by Rad52 foci and chromosome missegregation. Thus, in contrast to acute replication stress that triggers a sustained Mec1/ATR response, multiple pathways cooperate to restrain mitosis transiently when replication forks progress unhindered. We suggest that these surveillance mechanisms arose when both S and M phases were coincidently set into motion by a unique ancestral cyclin-Cdk1 complex.

  9. Identification of the minimal connected network of transcription factors by transcriptomic and genomic data integration.

    Science.gov (United States)

    Essaghir, Ahmed

    2014-01-01

    Thanks to high-throughput experiments, biological conditions can be investigated at both the entire genomic and transcriptomic levels. In addition, protein-protein interaction (PPI) data are widely available for well-studied organisms, such as human. In this chapter, we will present an integrative approach that makes use of these data to find the PPI module involving the key regulated transcription factors shared by a number of given conditions. These conditions could be for instance different cancer types. Briefly, for the studied conditions, we need to identify commonly affected chromosomal regions subjected to copy number alterations together with the identification of differentially expressed list of genes in each condition. Transcription factor activity will be inferred from these regulated gene lists. Then, we will define TFs, for which the activity could be explained by an associative effect of both loci copy number alteration and gene expression levels of their coding genes. PPI networks could be mined, afterwards, using appropriate algorithms to find the significant module that connect those TFs together. This module could be viewed as the minimal connected network of TFs, the regulation of which is shared between the investigated conditions.

  10. IMSA: integrated metagenomic sequence analysis for identification of exogenous reads in a host genomic background.

    Directory of Open Access Journals (Sweden)

    Michelle T Dimon

    Full Text Available Metagenomics, the study of microbial genomes within diverse environments, is a rapidly developing field. The identification of microbial sequences within a host organism enables the study of human intestinal, respiratory, and skin microbiota, and has allowed the identification of novel viruses in diseases such as Merkel cell carcinoma. There are few publicly available tools for metagenomic high throughput sequence analysis. We present Integrated Metagenomic Sequence Analysis (IMSA, a flexible, fast, and robust computational analysis pipeline that is available for public use. IMSA takes input sequence from high throughput datasets and uses a user-defined host database to filter out host sequence. IMSA then aligns the filtered reads to a user-defined universal database to characterize exogenous reads within the host background. IMSA assigns a score to each node of the taxonomy based on read frequency, and can output this as a taxonomy report suitable for cluster analysis or as a taxonomy map (TaxMap. IMSA also outputs the specific sequence reads assigned to a taxon of interest for downstream analysis. We demonstrate the use of IMSA to detect pathogens and normal flora within sequence data from a primary human cervical cancer carrying HPV16, a primary human cutaneous squamous cell carcinoma carrying HPV 16, the CaSki cell line carrying HPV16, and the HeLa cell line carrying HPV18.

  11. Transcription factor RFX1 is crucial for maintenance of genome integrity in Fusarium graminearum.

    Science.gov (United States)

    Min, Kyunghun; Son, Hokyoung; Lim, Jae Yun; Choi, Gyung Ja; Kim, Jin-Cheol; Harris, Steven D; Lee, Yin-Won

    2014-03-01

    The survival of cellular organisms depends on the faithful replication and transmission of DNA. Regulatory factor X (RFX) transcription factors are well conserved in animals and fungi, but their functions are diverse, ranging from the DNA damage response to ciliary gene regulation. We investigated the role of the sole RFX transcription factor, RFX1, in the plant-pathogenic fungus Fusarium graminearum. Deletion of rfx1 resulted in multiple defects in hyphal growth, conidiation, virulence, and sexual development. Deletion mutants of rfx1 were more sensitive to various types of DNA damage than the wild-type strain. Septum formation was inhibited and micronuclei were produced in the rfx1 deletion mutants. The results of the neutral comet assay demonstrated that disruption of rfx1 function caused spontaneous DNA double-strand breaks (DSBs). The transcript levels of genes involved in DNA DSB repair were upregulated in the rfx1 deletion mutants. DNA DSBs produced micronuclei and delayed septum formation in F. graminearum. Green fluorescent protein (GFP)-tagged RFX1 localized in nuclei and exhibited high expression levels in growing hyphae and conidiophores, where nuclear division was actively occurring. RNA-sequencing-based transcriptomic analysis revealed that RFX1 suppressed the expression of many genes, including those required for the repair of DNA damage. Taken together, these findings indicate that the transcriptional repressor rfx1 performs crucial roles during normal cell growth by maintaining genome integrity.

  12. BALSA: integrated secondary analysis for whole-genome and whole-exome sequencing, accelerated by GPU

    Directory of Open Access Journals (Sweden)

    Ruibang Luo

    2014-06-01

    Full Text Available This paper reports an integrated solution, called BALSA, for the secondary analysis of next generation sequencing data; it exploits the computational power of GPU and an intricate memory management to give a fast and accurate analysis. From raw reads to variants (including SNPs and Indels, BALSA, using just a single computing node with a commodity GPU board, takes 5.5 h to process 50-fold whole genome sequencing (∼750 million 100 bp paired-end reads, or just 25 min for 210-fold whole exome sequencing. BALSA’s speed is rooted at its parallel algorithms to effectively exploit a GPU to speed up processes like alignment, realignment and statistical testing. BALSA incorporates a 16-genotype model to support the calling of SNPs and Indels and achieves competitive variant calling accuracy and sensitivity when compared to the ensemble of six popular variant callers. BALSA also supports efficient identification of somatic SNVs and CNVs; experiments showed that BALSA recovers all the previously validated somatic SNVs and CNVs, and it is more sensitive for somatic Indel detection. BALSA outputs variants in VCF format. A pileup-like SNAPSHOT format, while maintaining the same fidelity as BAM in variant calling, enables efficient storage and indexing, and facilitates the App development of downstream analyses. BALSA is available at: http://sourceforge.net/p/balsa.

  13. Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline.

    Science.gov (United States)

    Pappas, Derek J; Marin, Wesley; Hollenbach, Jill A; Mack, Steven J

    2016-03-01

    Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org.

  14. Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology.

    Science.gov (United States)

    Karp, Peter D; Paley, Suzanne M; Krummenacker, Markus; Latendresse, Mario; Dale, Joseph M; Lee, Thomas J; Kaipa, Pallavi; Gilham, Fred; Spaulding, Aaron; Popescu, Liviu; Altman, Tomer; Paulsen, Ian; Keseler, Ingrid M; Caspi, Ron

    2010-01-01

    Pathway Tools is a production-quality software environment for creating a type of model-organism database called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction of metabolic pathways, prediction of metabolic pathway hole fillers and prediction of operons. It enables interactive editing of PGDBs by DB curators. It supports web publishing of PGDBs, and provides a large number of query and visualization tools. The software also supports comparative analyses of PGDBs, and provides several systems biology analyses of PGDBs including reachability analysis of metabolic networks, and interactive tracing of metabolites through a metabolic network. More than 800 PGDBs have been created using Pathway Tools by scientists around the world, many of which are curated DBs for important model organisms. Those PGDBs can be exchanged using a peer-to-peer DB sharing system called the PGDB Registry.

  15. Enabling the democratization of the genomics revolution with a fully integrated web-based bioinformatics platform

    Science.gov (United States)

    Li, Po-E; Lo, Chien-Chi; Anderson, Joseph J.; Davenport, Karen W.; Bishop-Lilly, Kimberly A.; Xu, Yan; Ahmed, Sanaa; Feng, Shihai; Mokashi, Vishwesh P.; Chain, Patrick S.G.

    2017-01-01

    Continued advancements in sequencing technologies have fueled the development of new sequencing applications and promise to flood current databases with raw data. A number of factors prevent the seamless and easy use of these data, including the breadth of project goals, the wide array of tools that individually perform fractions of any given analysis, the large number of associated software/hardware dependencies, and the detailed expertise required to perform these analyses. To address these issues, we have developed an intuitive web-based environment with a wide assortment of integrated and cutting-edge bioinformatics tools in pre-configured workflows. These workflows, coupled with the ease of use of the environment, provide even novice next-generation sequencing users with the ability to perform many complex analyses with only a few mouse clicks and, within the context of the same environment, to visualize and further interrogate their results. This bioinformatics platform is an initial attempt at Empowering the Development of Genomics Expertise (EDGE) in a wide range of applications for microbial research. PMID:27899609

  16. Integrated genome-scale prediction of detrimental mutations in transcription networks.

    Directory of Open Access Journals (Sweden)

    Mirko Francesconi

    2011-05-01

    Full Text Available A central challenge in genetics is to understand when and why mutations alter the phenotype of an organism. The consequences of gene inhibition have been systematically studied and can be predicted reasonably well across a genome. However, many sequence variants important for disease and evolution may alter gene regulation rather than gene function. The consequences of altering a regulatory interaction (or "edge" rather than a gene (or "node" in a network have not been as extensively studied. Here we use an integrative analysis and evolutionary conservation to identify features that predict when the loss of a regulatory interaction is detrimental in the extensively mapped transcription network of budding yeast. Properties such as the strength of an interaction, location and context in a promoter, regulator and target gene importance, and the potential for compensation (redundancy associate to some extent with interaction importance. Combined, however, these features predict quite well whether the loss of a regulatory interaction is detrimental across many promoters and for many different transcription factors. Thus, despite the potential for regulatory diversity, common principles can be used to understand and predict when changes in regulation are most harmful to an organism.

  17. The quail anatomy portal.

    Science.gov (United States)

    Ruparelia, Avnika A; Simkin, Johanna E; Salgado, David; Newgreen, Donald F; Martins, Gabriel G; Bryson-Richardson, Robert J

    2014-01-01

    The Japanese quail is a widely used model organism for the study of embryonic development; however, anatomical resources are lacking. The Quail Anatomy Portal (QAP) provides 22 detailed three-dimensional (3D) models of quail embryos during development from embryonic day (E)1 to E15 generated using optical projection tomography. The 3D models provided can be virtually sectioned to investigate anatomy. Furthermore, using the 3D nature of the models, we have generated a tool to assist in the staging of quail samples. Volume renderings of each stage are provided and can be rotated to allow visualization from multiple angles allowing easy comparison of features both between stages in the database and between images or samples in the laboratory. The use of JavaScript, PHP and HTML ensure the database is accessible to users across different operating systems, including mobile devices, facilitating its use in the laboratory.The QAP provides a unique resource for researchers using the quail model. The ability to virtually section anatomical models throughout development provides the opportunity for researchers to virtually dissect the quail and also provides a valuable tool for the education of students and researchers new to the field. DATABASE URL: http://quail.anatomyportal.org (For review username: demo, password: quail123).

  18. The Leptonic Higgs Portal

    CERN Document Server

    Batell, Brian; McKeen, David; Pospelov, Maxim; Ritz, Adam

    2016-01-01

    An extended Higgs sector may allow for new scalar particles well below the weak scale. In this work, we present a detailed study of a light scalar $S$ with enhanced coupling to leptons, which could be responsible for the existing discrepancy between experimental and theoretical determinations of the muon anomalous magnetic moment. We present an ultraviolet completion of this model in terms of the lepton-specific two-Higgs doublet model and an additional scalar singlet. We then analyze a plethora of experimental constraints on the universal low energy model, and this UV completion, along with the sensitivity reach at future experiments. The most relevant constraints originate from muon and kaon decays, electron beam dump experiments, electroweak precision observables, rare $B_d$ and $B_s$ decays and Higgs branching fractions. The properties of the leptonic Higgs portal imply an enhanced couplings to heavy leptons, and we identify the most promising search mode for the high-luminosity electron-positron collider...

  19. Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome

    Directory of Open Access Journals (Sweden)

    Pin Cui

    2016-03-01

    Full Text Available Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV is currently invading the germline of the koala (Phascolarctos cinereus and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small.

  20. Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes

    Energy Technology Data Exchange (ETDEWEB)

    Mushegian, Arcady R., E-mail: mushegian2@gmail.com [Division of Molecular and Cellular Biosciences, National Science Foundation, 4201 Wilson Boulevard, Arlington, VA 22230 (United States); Elena, Santiago F., E-mail: sfelena@ibmcp.upv.es [Instituto de Biología Molecular y Celular de Plantas, CSIC-UPV, 46022 València (Spain); The Santa Fe Institute, Santa Fe, NM 87501 (United States)

    2015-02-15

    Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by diverse plant viruses. Mechanisms of action and evolutionary origins of these proteins remain obscure. We expand the picture of conservation and evolution of the 30K proteins, producing sequence alignment of the 30K superfamily with the broadest phylogenetic coverage thus far and illuminating structural features of the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K movement genes are prevalent in euphyllophytes, with at least one copy intact in nearly every examined species, and mRNAs detected for most of them. Sequence analysis suggests repeated integrations, pseudogenizations, and positive selection in those provirus genes. An unannotated 30K-superfamily gene in Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113 transcript. This molecular background of endopararetrovirus gene products in plants may change our view of virus infection and pathogenesis, and perhaps of cellular homeostasis in the hosts. - Highlights: • Sequence region shared by plant virus “30K” movement proteins has an all-beta fold. • Most euphyllophyte genomes contain integrated copies of pararetroviruses. • These integrated virus genomes often include intact movement protein genes. • Molecular evidence suggests that these “30K” genes may be selected for function.

  1. Differential methylation of E2 binding sites in episomal and integrated HPV 16 genomes in preinvasive and invasive cervical lesions.

    Science.gov (United States)

    Chaiwongkot, Arkom; Vinokurova, Svetlana; Pientong, Chamsai; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Kleebkaow, Pilaiwan; Chumworathayi, Bandit; Patarapadungkit, Natcha; Reuschenbach, Miriam; von Knebel Doeberitz, Magnus

    2013-05-01

    Enhanced expression of the HPV 16 E6-E7 oncogenes may trigger neoplastic transformation of the squamous epithelial cells at the uterine cervix. The HPV E2 protein is a key transcriptional regulator of the E6-E7 genes. It binds to four E2 binding sites (E2BSs 1-4) in the viral upstream regulatory region (URR). Modification of E2 functions, for example, by methylation of E2BSs is hypothesized to trigger enhanced expression of the viral E6-E7 oncogenes. In the majority of HPV-transformed premalignant lesions and about half of cervical carcinomas HPV genomes persist in an extra-chromosomal, episomal state, whereas they are integrated into host cells chromosomes in the remaining lesions. Here we compared the methylation profile of E2BSs 1-4 of the HPV 16 URR in a series of 18 HPV16-positive premalignant lesions and 33 invasive cervical cancers. CpGs within the E2BSs 1, 3, and 4 were higher methylated in all lesions with only episomal HPV16 genomes compared with lesions displaying single integrated copies. Samples with multiple HPV16 integrated copies displayed high methylation levels for all CpGs suggesting that the majority of multiple copies were silenced by extensive methylation. These data support the hypothesis that differential methylation of the E2BSs 1, 3 and 4 is related to the activation of viral oncogene expression in cervical lesions as long as the viral genome remains in the episomal state. Once the virus becomes integrated into host cell chromosomes these methylation patterns may be substantially altered due to complex epigenetic changes of integrated HPV genomes.

  2. Retroviral integration process in the human genome: is it really non-random? A new statistical approach.

    Directory of Open Access Journals (Sweden)

    Alessandro Ambrosi

    Full Text Available Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells, since, once delivered to the nucleus, the genes of interest are stably inserted (integrated into the target cell genome. There is now compelling evidence that integration of retroviral vectors follows non-random patterns in mammalian genome, with a preference for active genes and regulatory regions. In particular, Moloney Leukemia Virus (MLV-derived vectors show a tendency to integrate in the proximity of the transcription start site (TSS of genes, occasionally resulting in the deregulation of gene expression and, where proto-oncogenes are targeted, in tumor initiation. This has drawn the attention of the scientific community to the molecular determinants of the retroviral integration process as well as to statistical methods to evaluate the genome-wide distribution of integration sites. In recent approaches, the observed distribution of MLV integration distances (IDs from the TSS of the nearest gene is assumed to be non-random by empirical comparison with a random distribution generated by computational simulation procedures. To provide a statistical procedure to test the randomness of the retroviral insertion pattern, we propose a probability model (Beta distribution based on IDs between two consecutive genes. We apply the procedure to a set of 595 unique MLV insertion sites retrieved from human hematopoietic stem/progenitor cells. The statistical goodness of fit test shows the suitability of this distribution to the observed data. Our statistical analysis confirms the preference of MLV-based vectors to integrate in promoter-proximal regions.

  3. Genomics and Integrated Systems Biology in Plasmodium falciparum: A Path to Malaria Control and Eradication

    Science.gov (United States)

    Le Roch, Karine G.; Chung, Duk-Won D.; Ponts, Nadia

    2011-01-01

    The first draft of the human malaria parasite's genome was released in 2002. Since then, the malaria scientific community has witnessed a steady embrace of new and powerful functional genomic studies. Over the years, these approaches have slowly revolutionized malaria research and enabled the comprehensive, unbiased investigation of various aspects of the parasite's biology. These genome-wide analyses delivered a refined annotation of the parasite's genome, a better knowledge of its RNA, proteins, and metabolite derivatives, and fostered the discovery of new vaccine and drug targets. Despite the positive impacts of these genomic studies, most research and investment still focus on protein targets, drugs and vaccine candidates that were known before the publication of the parasite genome sequence. However, recent access to next-generation sequencing technologies, along with an increased number of genome-wide applications are expanding the impact of the parasite genome on biomedical research, contributing to a paradigm shift in research activities that may possibly lead to new optimized diagnosis and treatments. This review provides an update of Plasmodium falciparum genome sequences and an overview of the rapid development of genomics and system biology applications that have an immense potential of creating powerful tools for a successful malaria eradication campaign. PMID:21995286

  4. 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

    Full Text Available Abstract Background To facilitate efficient selection and the prioritization of candidate complex disease susceptibility genes for association analysis, increasingly comprehensive annotation tools are essential to integrate, visualize and analyze vast quantities of disparate data generated by genomic