06 November 2011 Richard H. Scheuermann, Ph.D. Department of Pathology

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www.viprbrc.org. Influenza Research Database (IRD) & Virus Pathogen Resource ( ViPR ) Bioinformatics Resource Centers ( BRCs ) and support for Systems Biology data. 06 November 2011 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center. ViPR Overview. - PowerPoint PPT Presentation

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Influenza Research Database (IRD) & Virus Pathogen Resource (ViPR) Bioinformatics Resource Centers (BRCs) and support for Systems Biology data06 November 2011

Richard H. Scheuermann, Ph.D.Department of PathologyU.T. Southwestern Medical Center

www.viprbrc.orgwww.fludb.orgViPR Overview

www.viprbrc.orgwww.fludb.orgIRD Overview

www.fludb.orgwww.fludb.orgData Summary & Sources

www.fludb.orgData from both public archives (e.g. GenBank, PDB) and novel data derived by IRD through core data analysis and manual curationGenBank data loaded on a daily basisOther loads based on data refresh frequencies of source archives4Search Access to Data

www.fludb.orgwww.fludb.orgData accessed through optimized search interfaces5Data Types

www.fludb.orgSearch pages for various different data types6Analysis and Visualization

www.fludb.orgwww.fludb.orgLink to list of analysis and visualization tools7Analysis and Visualization Tools

www.fludb.orgCurrent analysis tools focused on comparative genomicsEmphasis placed on data integration for visualization8Workbench Access

www.fludb.orgwww.fludb.orgLink to personal workbench to save working sets of sequence and surveillance records, and analysis results9Data Submission

www.fludb.orgwww.fludb.orgLink to personal workbench to save working sets of sequence and surveillance records, and analysis results10Data Submission Page

www.fludb.orgSystems Biology Omics Datawww.fludb.orgOverview of Systems Biology & DBP ProjectsFour systems biology groups funded by NIAID, including:Systems Virology (Michael Katze group, Univ. Washington)Influenza H1N1 and H5N1 and SARS Coronavirusstatistical models, algorithms and software, raw and processed gene expression data, and proteomics dataSystems Influenza (Alan Aderem group, Institute for Systems Biology)various Influenza virusesmicroarray, mass spectrometry, and lipidomics dataViPR Driving Biological ProjectsAbraham Brass, Mass. General HospitalDengue virus host factor database from RNAi screen Lynn Enquist / Moriah Szpara, Princeton UniversityDeep sequencing and neuronal microarrays for functional genomic analysis of Herpes Simplex Viruswww.fludb.org

Andrew R. Joyce & Bernhard . Palsson, Nature Reviews Molecular Cell Biology 7, 198-210 (March 2006)Omics Datawww.fludb.orgSome biological insight into omics data integration14AcknowledgementLynn Law, U. WashingtonRichard Green, U. WashingtonJyothi Noronha, U.T. SouthwesternEva Sadat, U.T. SouthwesternBrett Pickett, U.T. Southwesternwww.fludb.orgDiscussion PointsRelationship between data archives (e.g. GEO, PRIDE) and the BRCs (e.g. IRD, ViPR, PATRIC)IntegrationMetadata standardsMetadataWhat kind of dataWhat kind of standards MIBBI vs. MIBBI liteRaw versus processed dataPrimary results dataNeed to define what is considered primary data for each platformMicroarray example: raw image files (.tiff) vs probe intensity values (.cel)Opportunity for re-processing leading to re-interpretationDerived/processed resultsInteresting gene/protein lists from microarray, RNAi, proteomics, and other experimental platformsInteresting metabolite listsData processing metadataVisualize and analyze interesting gene/protein/metabolite listswww.fludb.orgOmics data management (host)Project metadataExperiment metadataExperiment sample metadataData analysis metadataPrimary resultsDerived results (e.g. interesting gene/protein/metabolite lists (Host Factor Biosets))Add additional related datasets from other sources Visualize Host Factor Biosets in context of biological pathways and networksStatistical analysis of pathway sub-network overrepresentationRe-analysis of primary data using assembled pipeline tools (?)Proposal for Omics Datawww.fludb.orgGEO Representation

GEO data representations based on free textwww.fludb.orgNon-standard Descriptions

Guess samples details

www.fludb.org Metadata (MIBBI-compliant)Project Level MetadataHypothesis, rationale, study design, etc.Publications and links pertaining to the projectData providers - PI, other key personnel, affiliations, contact informationExperiment/Assay Level MetadataExperiment platformExperiment data typeExperiment Sample Level MetadataSample source and characteristics of sourceSample typeSource/sample treatment informationAssay detailsData Processing/Analysis Level MetadataAlgorithm(s) used for transforming primary to derived dataConfiguration parameterswww.fludb.orgMetadata Submission ModulesStudyExperimentAnimal/human subjectBiosampleReagentProtocolExperiment SampleAnalysis methodHost factor biosetwww.fludb.org

Studywww.fludb.org

Experimentwww.fludb.org

Subjectwww.fludb.org

Biosamplewww.fludb.org

Reagentwww.fludb.org

Protocolwww.fludb.org

Experiment Samplewww.fludb.org

Analysis Methodwww.fludb.org

Host Factor Biosetwww.fludb.orgPossible Data Submission WorkflowsStudy metadataExperiment sample metadataPrimary resultsAnalysis metadataHost factor biosetGEO free text metadataGEOViPR/IRDPrimary resultsStudy metadataExperiment sample metadataPrimary resultsAnalysis metadataHost factor biosetGEO free text metadataGEOViPR/IRDABStudy metadataExperiment sample metadataPrimary resultsAnalysis metadataHost factor biosetGEO free text metadataGEOViPR/IRDPrimary resultsCwww.fludb.org

Search Analyze Save to WorkbenchSearch our robust database for: Genomes Genes & proteins Immune epitopes 3D protein structuresAnalyze your results online. We offer: Identify similar sequences (BLAST) Align sequences (MSA) Find short peptides in proteins Visualize aligned sequencesSign up for a Workbench to: Store data in working sets for future analysis Integrate ViPR data with your laboratory data Store analysis results Share results and data with collaboratorsBrowse All Search TypesBrowse All ToolsSign Up!Sign InVirus Taxonomy BrowserClick on family or species of interest in taxonomy below to view viral genomes, or click here to view in list format.HighlightsViPR Highlight for All FamiliesYou can now search for, and visualize, 3D protein structures from within the ViPR website. Simply navigate to the protein of interest and then follow the links to use this feature.

View Tutorial View Example Results Start Search

Family:Arenaviridae(1 Genus)Family:Bunyaviridae(4 Genera)Family:Caliciviridae(5 Genera)Family:Coronaviridae(2 Subfamilies)Family:Filoviridae(2 Genera)Family:Flaviviridae(3 Genera)Family:Hepeviridae(1 Genus)Family:Herpesviridae(3 Subfamilies)Family:Paramyxoviridae(2 Subfamilies)Family:Picornaviridae(1 Genus)Family:Poxviridae(2 Subfamilies)Family:Rhabdoviridae(1 Genus)Family:Togaviridae(1 Genus)Data Summary Updated 2 Weeks AgoGenome Statistics for Virus FamiliesFamilies13Genera54Species661Strains38,886Segments45,154Community SpotlightThe ViPR database is pleased to announce the progress of the Driving Biological Projects (DBPs). As results become available, we will incorporate them into our database for easy access and use from the scientific community.

ViPR welcomes feedback, contributions, and collaborations from the scientific community on how we can improve our resource.FAMILY_NAMETEXT SEARCHGenomesGenes & ProteinsImmune EpitopesHost Factor Biosets3D Protein StructuresProtein DomainsProtein MotifsHISTORYYour Analysis HistoryRetrieve a DownloadOrtholog GroupsSEARCH OR FIND:Quick Text SearchSequence Feature Variant Type

ViPRVirus Pathogen Resource

...About Us Supported Projects Announcements Resources SupportSEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEwww.fludb.org

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEYou are logged in as username@domain.eduSign OutHost Factor BiosetsBack to Previous Page Please Select an Experiment to Explore to view the associated Bioset (Interesting Gene List )Study TitleExperiment NameExperiment TypeHost Species & Biomaterial (Cell Line)Virus Strain NameHost factors in DENV replicationDengue whole-genome siRNA library screensiRNA ScreenHuman (Huh-7)New Guinea C

About Us Supported Projects Announcements Resources SupportPIPI InstitutionContract / Grant TitleDescriptionKeywordsContract / Grant NumberDate SubmittedAbraham L. BrassMassachusetts General HospitalDengue Virus-Host Interactiosn Using Functional GenomicsIdentify host factors required for DENV replication by using siRNA libraries. Dengue, DENV, siRNA, host factorsHHSN135711131(NIAID)Dec 2011Cite ViPR Tutorials Report a Bug Request Web Training Contact UsRelease Date: Jan 7, 2012This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.Study TitleExperiment NameExperiment TypeHost Species & Biomaterial (Cell Line)Virus Strain NameHost factors in HSV-1 replicationHost neuronal response to HSV-1 Gene Expression MicroarrayHuman Neurons(SHSY5Y )17

PIPI InstitutionContract / Grant TitleDescriptionKeywordsContract / Grant NumberDate SubmittedMoriah SzparaLynn EnquistPrinceton Univ.Deep Sequencing and Neuronal Microarrays for Functional Genomic Analysis of HSV-1 Characterize the response to HSV-1 infection through differential gene expression in human neuronal cells.Herpes Simplex Virus 1, HSV-1, neurons, HHSN24681012(NIAID)Apr 2012www.fludb.orgA list of all experiments available performed as part of the DENV DBP. This list would be the one displayed if accessing the Host Factor Biosets Module by clicking on the Driving Biological Projects option under the Supported Projects menu.33

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEAbout Us Announcements Resources SupportYou are logged in as username@domain.eduSign OutHost Factor Biosets(Omics Experiment Details)Download Host FactorsDownload AllDownload Primary ResultsEXPERIMENT METADATA (from Host response to Influenza virus infection)-PRIMARY RESULTS-HOST FACTOR BIOSETS+Experiment Sample IDSource Biological SampleTreatment Agent 1 NameTreatment Agent 1 AmountTreatment 1 DurationDownload Experiment Data251485048497_1_2_RNACalu-3 cellsA/Vietnam/1203-CIP048_RG1/2004(H5N1)1 MOI0 hrsExperiment Sample 1251485048466_1_3_RNACalu-3 cellsA/Vietnam/1203-CIP048_RG1/2004(H5N1)1 MOI12 hrsExperiment Sample 2251485048497_1_1_RNACalu-3 cellsA/Vietnam/1203-CIP048_RG1/2004(H5N1)1 MOI24 hrsExperiment Sample 3251485048467_1_1_RNACalu-3 cellsMockMock24 hrsExperiment Sample 4Study TitleExperiment NameExperiment TypeHost Species & Biomaterial (Cell Line)Virus Strain NameConditional VariablesNIAID Systems Virology CenterVN1203/2004 infection in Calu3 cell: A time courseGene Expression MicroarrayCalu3A/Vietnam/1203-CIP48_RG1/2004(H5N1)+/- virus infection, time after infectionwww.fludb.org34Gene NameEntrez Gene IDEntrez Gene NameImmPort PageGenBank AccessionBioset 1ScoreBioset 2ScoreMus musculus contactin 112805Cntn1NM_0077270.5881310.812506913Mus musculus preproenkephalin 118619Penk1NM_0010029270.2774877260.920335884Mus musculus 5-hydroxytryptamine (serotonin) receptor 715566Htr7NM_008315NS0.078352547Cite ViPR Tutorials Report a Bug Request Web Training Contact UsRelease Date: Jan 7, 2012This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEAbout Us Announcements Resources SupportYou are logged in as username@domain.eduSign OutHost Factor Biosets(Omics Experiment Details)Run Analysis Download Host FactorsDownload AllDownload Primary Results

Bioset NameDescription of BiosetBioset TypeName of Application or Analysis MethodDownload Bioset DataCompendium_Digital_signature_by_Fishers_summary_statisticFrom a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS-CoV, we used meta-analysis to derive multiple gene expression signatures. Meta-analysisFishers summary-statistic: MADAM (Meta-Analysis Data Aggregation Methods)Bioset 1Microarray_results_flu_calu-3Included RNA isolated from cells infected with influenza A subtype H5N1 at various timepointsList of differentially expressed genesInter-array normalization;Median-background subtractionBioset 2+PRIMARY RESULTS+HOST FACTOR BIOSETS-

EXPERIMENT METADATA (from Host response to Influenza virus infection)

www.fludb.org35Gene NameEntrez Gene IDEntrez Gene NameImmPort PageGenBank AccessionBioset 1ScoreBioset 2ScoreMus musculus contactin 112805Cntn1NM_0077270.5881310.812506913Mus musculus preproenkephalin 118619Penk1NM_0010029270.2774877260.920335884Mus musculus 5-hydroxytryptamine (serotonin) receptor 715566Htr7NM_008315NS0.078352547Cite ViPR Tutorials Report a Bug Request Web Training Contact UsRelease Date: Jan 7, 2012This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEAbout Us Announcements Resources SupportYou are logged in as username@domain.eduSign OutHost Factor Biosets(Omics Experiment Details)Download Host FactorsDownload AllDownload Primary Results

Bioset NameDescription of BiosetBioset TypeName of Application or Analysis MethodDownload Bioset DataCompendium_Digital_signature_by_Fishers_summary_statisticFrom a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS-CoV, we used meta-analysis to derive multiple gene expression signatures. Meta-analysisFishers summary-statistic: MADAM (Meta-Analysis Data Aggregation Methods)Bioset 1Microarray_results_flu_calu-3Included RNA isolated from cells infected with influenza A subtype H5N1 at various timepointsList of differentially expressed genesInter-array normalization;Median-background subtractionBioset 2+PRIMARY RESULTS+HOST FACTOR BIOSETS-

EXPERIMENT METADATA (from Host response to Influenza virus infection)

Visualize Protein NetworkRun Analysis

www.fludb.org36Gene NameEntrez Gene IDEntrez Gene NameImmPort PageGenBank AccessionBioset 1ScoreBioset 2ScoreMus musculus contactin 112805Cntn1NM_0077270.5881310.812506913Mus musculus preproenkephalin 118619Penk1NM_0010029270.2774877260.920335884Mus musculus 5-hydroxytryptamine (serotonin) receptor 715566Htr7NM_008315NS0.078352547Cite ViPR Tutorials Report a Bug Request Web Training Contact UsRelease Date: Jan 7, 2012This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEAbout Us Announcements Resources SupportYou are logged in as username@domain.eduSign OutHost Factor Biosets(Omics Experiment Details)Download Host FactorsDownload AllDownload Primary Results

Bioset NameDescription of BiosetBioset TypeName of Application or Analysis MethodDownload Bioset DataCompendium_Digital_signature_by_Fishers_summary_statisticFrom a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS-CoV, we used meta-analysis to derive multiple gene expression signatures. Meta-analysisFishers summary-statistic: MADAM (Meta-Analysis Data Aggregation Methods)Bioset 1Microarray_results_flu_calu-3Included RNA isolated from cells infected with influenza A subtype H5N1 at various timepointsList of differentially expressed genesInter-array normalization;Median-background subtractionBioset 2-PRIMARY RESULTS+HOST FACTOR BIOSETS-

EXPERIMENT METADATA (from Host response to Influenza virus infection)

Visualize Protein NetworkRun Analysis

ViPR Protein-Protein Interactions and Pathway VisualizationPlease choose the type of data that you would like to view relating to your selection(s):First-Degree (Direct) Interactions

Second-Degree Interactions

Functional Modules

Metabolic PathwaysVisualizeCancelwww.fludb.org37

ViPRVirus Pathogen Resource

SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOMEFAMILY_NAMEAbout Us Announcements Resources SupportYou are logged in as username@domain.eduSign OutCite ViPR Tutorials Report a Bug Request Web Training Contact UsRelease Date: Jan 20, 2011This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.Visualize Host Factor InteractionsPROTEIN-PROTEIN INTERACTIONS INFORMATIONNumber of hits from Interesting Gene List:1Number of Nodes: $num_nodesNumber of Edges: $num_edgesSave Analysiswww.fludb.org39U.T. SouthwesternRichard Scheuermann (PI)Burke SquiresJyothi NoronhaVictoria HuntEva SadatBrett PickettYun ZhangVecnaChris LarsenAl RamseyLANLCatherine MackenMira DimitrijevicU.C. DavisNicole BaumgarthUSDADavid Suarez Sage AnalyticaRobert TaylorLone SimonsenU. WashingtonMichael Gale

Northrop GrummanEd KlemMike AtassiJon DietrichPatty BergerJawwad CheemaZhiping GuSherry HeWenjie HuaWei JenSanjeev KumarXiaomei LiJason LucasBruce QuesenberryBarbara RotchfordPrabhu ShankarHongbo SuBryan WaltersSam ZarembaLiwei Zhou

U. WashingtonLynn LawRichard Green

IRD SWGGillian Air, OMRFCarol Cardona, Univ. MinnesotaAdolfo Garcia-Sastre, Mt SinaiElodie Ghedin, Univ. PittsburghMartha Nelson, FogartyDaniel Perez, Univ. MarylandGavin Smith, Duke SingaporeDave Stallknecht, Univ. GeorgiaDavid Topham, RochesterRichard Webby, St JudeViPR SWGRichard Kuhn, PurdueRaul Andino, UCSFSlobodan Paessler, UTMB GalvestonX.J. Meng, VBIColin Parrish, CornellElliot Lefkowitz, UABCarla Kuiken, LANLDavid Knipe, HarvardMatthew Henn, Broad InstituteRichard Whitley, UABJohn Young, Salk Institute

Acknowledgments N01AI40041N01AI2008038www.fludb.org39

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