1 Immunology Database and Analysis Portal ImmPort www.immport.org www.immport.org Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern.

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  • *Immunology Database and Analysis PortalImmPortwww.immport.org Richard H. Scheuermann, Ph.D.Department of PathologyU.T. Southwestern Medical Center

    16 DEC 2010

  • ImmPort Purpose and History NIH/NIAID/DAIT would like to:maximize the return on the public investment in basic, translational and clinical researchallow investigators to more effectively extract meaningful information from the vast amounts of data generated from advanced research technologies=> data sharing policy

    Bioinformatics Integration Support Contract (BISC) to support data sharing for all DAIT-funded programs - basic, translational and clinical research

    Immunology Database and Analysis Portal (ImmPort) - www.ImmPort.org Archive and manage basic and clinical research dataIntegrate these research data with extensive biological knowledgeSupport analysis of these integrated data

  • Take-home messagesImmPort has been tailored to support the needs of the immunology research communityComprehensive integrated resource for the capture, support and analysis of a wide range of basic, translational and clinical research dataCompliant with established and emerging data standards, e.g. MIAME, MIFlowCyt, Cell OntologyWork collaboratively with system users to develop and implement novel data processing and analysis methods

  • Tailored for immunologyBuilt by Immunologists for Immunologists

  • VignettesHLA Region Genetics ConsortiumHLA typing ambiguity reduction pipelineHLA sequence feature definition and variant type analysis and visualizationPyPop-based genetic analysisNovel methods and infrastructure for flow cytometry analysis FLOCKComprehensive support for clinical and translational research design and results data Casale/ITN

  • www.immport.org

  • Reference and research data

  • Visualization tools

  • Analysis tools

  • WorkspacesPublicReference dataAccessible without registration or log inSemi-publicResearch data released after publicationAccess to analytical toolsRegistration and log in required for accessAccessible to all registered usersPrivatePre-publication research dataAccess controlled by P.I. (or P.M.)CollaborativeControlled sharing of research data

  • VignettesHLA Region Genetics ConsortiumHLA typing ambiguity reduction pipelineHLA sequence feature definition and variant type analysis and visualizationPyPop-based genetic analysisNovel methods and infrastructure for flow cytometry analysis FLOCKComprehensive support for clinical and translational research design and results data Casale/ITN

  • *Summary of SFVT approachTraditional HLA allele association analysis treats entire allele as a single unit and does not capture the structural relationships between allelesSequence Feature Variant Type (SFVT) approach Define individual sequence features (SF) in HLA proteins (genes)Determine the extent of polymorphism for each sequence feature by defining the observed variant types (VT)Re-annotate HLA typing information with complete list of VT for each SFExamine the association between every sequence feature variant type and disease or other phenotype

  • Representative Sequence Features

  • *A*0201 - CD8 binding &TCR binding SF

  • Summary of SFs defined1775 total

  • Variant Types for Hsa_HLA-DRB1_beta-strand 2_peptide antigen binding

  • Publicationprotective risk

  • *ImmPort HLA SFVT Workflow

  • HLA Typing Platforms and AmbiguityHLA Typing PlatformsSSOP single-stranded oligonucleotide probeSSP sequence-specific primingSBT sequence-based typingSSCP single-stranded conformation polymorphismAllelic AmbiguityTyping methodology cannot distinguish between sets of allelesPolymorphisms that distinguish these alleles are not interrogated by the method Outside of exon 2 (class II) or exons 2 and 3 (class I) Sections of these exons not covered by the probes/primersGenotypic AmbiguityInability to determine phase in heterozygous samples

  • Ambiguity in HLA Typing Data

  • Allelic Ambiguity ReductionEliminate othersAre any of the alleles reg-CWD?Elimination of less-probable alleles by CWD statusReduction of multiple alleles to G- or P-codesyesnoEliminate othersAre any of the alleles CWD?yesnoEliminate othersAre any of the alleles reg-Rare?yes

  • Outcome of HLA Ambiguity ReductionAllelic Ambiguity ReductionGenotypic Ambiguity Reduction

  • VignettesHLA Region Genetics ConsortiumHLA typing ambiguity reduction pipelineHLA sequence feature definition and variant type analysis and visualizationPyPop-based genetic analysisNovel methods and infrastructure for flow cytometry analysis FLOCKComprehensive support for clinical and translational research design and results data Casale/ITN

  • Flow Cytometry AnalysisFLOCK is an algorithmic application for the identification of unique cell populations in multi-dimensional flow cytometry dataN1-3UM1-2UM3-4PBGSMGNSMDNMCD27IgDA

  • Population statistics

  • Summary Statistics

  • B cell component of the Cell Ontologyhttp://www.obofoundry.org/

  • FlowCAP

  • VignettesHLA Region Genetics ConsortiumHLA typing ambiguity reduction pipelineHLA sequence feature definition and variant type analysis and visualizationPyPop-based genetic analysisNovel methods and infrastructure for flow cytometry analysis FLOCKComprehensive support for clinical and translational research design and results data Casale/ITN

  • 5+ DAIT-funded ProgramsImmune Function and Biodefense in Children, Elderly, and Immunocompromised Populations ProgramPopulation Genetics Analysis Program: Immunity to Vaccines/Infections ProgramHLA Region Genetics in Immune-Mediated Diseases ProgramOther Consortium ProjectsImmune Modeling CentersImmPort Research Data | My Work BenchBrowse Data/ ImmPort Research Data/ ImmPort Supported ProgramsReagent Development for Toll-like and other Innate Immune Receptors

    DMID-funded Centers of Excellence for Influenza Research and Surveillance

    GlaxoSmithKline COPD trial34 Projects, >100,000 subjects, terabytes of FCM, microarray, SNP genotype, ELISA, ELISPOT, etc. data

  • PopGenGrants/Contracts/Projects:Population Genetics Analysis Program: Immunity to Vaccines/Infections ProgramImmPort Research Data | My Work BenchBrowse Data/ ImmPort Research Data/ ImmPort Supported Programs

    Project Title Institute Principle Investigator Objective Number of Subjects Mechanistic Assays StatusImmunity to Vaccinia Virus Infection Mayo Clinic Gregory A. Poland, M.D .To correlate variability in humoral and cell-mediated immune responses to vaccinia virus immunization with genetic variation in the HLA, cytokine and cytokine receptor genes and the broader genome. 1,076ELISA, ELISPOT, HLA genotype, GWAS, Microarray, Flow Cytometry Completely loaded in PPWPopulation Genetics Program on West Nile Virus Project McMaster University Mark Loeb, Ph.D. Gene analysis using Illumina Human NS-12 and Omni 1, single nucleotide polymorphisms (SNPs) to compare gene frequencies between individuals with meningoencephalitis and those with West Nile Fever using a case-control study design. 1,346Infinium assay, sequenom, whole-genome expression Completely loaded in PPW

    Immunity to Vaccines/Infections Immune Response Polymorphisms: Smallpox, Tuberculosis, Influenza and Common Encapsulated Bacteria Infections deCODE Genetics Jeffrey Gulcher, M.D., Ph.D. To map, isolate and validate human host genes that confer risk of either adverse reactions to smallpox vaccination or lack of specific immune response to the vaccine. 90,037genotyping, mRNA expression, GWAS Partially loaded in PPW

    Immune Response Polymorphisms: Typhoid/Cholera Vaccines RTI International Diane Wagener, Ph.D. To understand role of polymorphisms in genes of innate and adaptive immunity in modulating the response to typhoid vaccine. 2000Sequencing , ELISA, Mass spectrometry, multiplex bead assay, gel electrophoresis, shotgun proteomics, vibriocidal assay Completely loaded in PPW

    Genetic Risk for Smallpox Vaccine Related to Myocarditis University of Washington Christopher B. Wilson, M.D. To identify genetic differences that increase the risk for a major adverse event associated with smallpox vaccination - myocarditis - and to determine the mechanism by which these genetic differences confer risk Unknown? SNP Array Genotyping, HLA genotyping Completely loaded in PPW

    Genetic Factors and Immune Response to Anthrax Vaccine Univerity of Alabama at Birmingham, Birmingham AL Richard Kaslow, M.D. To investigate variability in host genes predicting variation in antibody responses and adverse reactions to Anthrax Vaccine Adsorbed (AVA). 1453ELISA, Flow Cytometry, Pyrosequencing, Gene expression Completely loaded in PPW

  • Special PopsGrants/Contracts/Projects:Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations ProgramImmPort Research Data | My Work BenchBrowse Data/ ImmPort Research Data/ ImmPort Supported Programs

    Project TitleInstitutionPrinciple InvestigatorObjectiveNumber of SubjectsMechanistic AssaysStatusAn Improved Influenza A Vaccine for Rapid Protection of the ElderlyThe Wistar InstituteHildegund C. J. Ertl, M.D.To conduct pre-clinical studies needed to develop a vaccine for the elderly that would provide protection in the event of a bioterror attack with influenza A virus.600ELISA, ELISPOT, Flow CytometryPartially loaded in PPWProtective Immunity in Transplant RecipientsEmory Transplant CenterLarsen, Christian, Ph.D.To determine the effects of chronic immunosuppressive therapies on adaptive, innate and specific immunity90ELISA, ELISPOT, Microarry, RT - PCRPartially loaded in PPWKinetic analysis of immunologic repletion and influenza vaccine responsivenessChildrens Hospital of PhiladelphiaSullivan, Kathleen, Ph.D.To propose a comprehensive analysis of the immunologic response to killed trivalent influenza vaccine in different immunocompromised populations in order to understand how to improve vaccine responses54ELISPOT, Sequencing, Flow CytometryPartially loaded in PPWImmune Function and Biodefense in Children, Elderly, and Immunocompromised Populations: TLRs in Innate Immunity and the Induction of Adaptive Immunity in the Neonate and InfantUniversity of WashingtonHajjar, Lynn, M.D.To define comprehensively and in molecular and cellular detail differences in recognition and response to microbe-derived danger signals between adults, neonates and infants, and how these, in turn, contribute to differences in innate immunity and the induction of antigen-specific (adaptive) immunity17 adults, 17 neonatesRT-PCR, ELISA, Flow Cytometry, MicroarrayPartially loaded in PPWResponses to Influenza Vaccination in Systemic LupusOklahoma Medical Research Foundation (OMRF)Thompson, Linda, Ph.D.To understand why many patients with systemic lupus erythematosus (SLE) fail to make adequate responses to immunization with the influenza vaccine.60ELISPOT, ELISA, multiplex RT-PCRPartially loaded in PPWImmune function and Biodefense in Children, Elderly and Immunocompromised PopulationsOregon Health and Science UniversityNikolich-Zugich, Janko, M.D., Ph.D.To characterize immune markers and mechanisms in the elderly that determine their vulnerability to infectious and bioterrorism agents in categories A-C.130Flow Cytometry, ELISA, RT-PCR, Gene expression, Partially loaded in PPWImmune Response to Virus Infection During PregnancyMt. Sinai School of MedicineMoran, Thomas, Ph.D.To determine whether the different trimesters of pregnancy, characterized by unique hormonal environments, are associated with (a) identifiable, discrete changes in maternal systemic immunity and/or (b) recognizable alterations in susceptibility to select bio-defense pathogens and/or (c) differential responses to influenza vaccination75Flow Cytometry, multiplex ELISA, RT-PCRPartially loaded in PPWRochester BiodefenseUniversity of RochesterSanz, Ignacio, M.D.To identify the specific immune defects that make immunocomprised populations specially susceptible at bioterrorists attack.280Flow CytometryPartially loaded in PPWInnate Immune Responsiveness in the Elderly and the Immunosuppressed Yale School of MedicineMontgomery, Ruth, M.D.,Erol Fikrig, MDThis proposal will explore the hypothesis that altered innate immune responsiveness in the elderly and the immunosuppressed contributes to vaccine unresponsiveness or disease susceptibility.1160SNP genotyping, Flow Cytometry, ELISAPartially loaded in PPW

  • Consortium ProjectsGrants/Contracts/Projects:Other Consortium ProjectsImmPort Research Data | My Work BenchBrowse Data/ ImmPort Research Data/ ImmPort Supported Programs

    Project TitleInstitutePrinciple InvestigatorObjectiveNumber of SubjectsMechanistic AssayStatusAllergen immunotherapy Co-administered with Omalizumab shared to Semi-Public Workspace (SPW) ProjectImmune Tolerance Network Group (ITN)Thomas CasaleTo determine whether taking a drug called omalizumab (also known as Xolair) before getting the allergy shots is more effective than allergy shots alone or other treatments, such as prescription antihistamines. 159Flow cytometry, ELISACompletely available in SPWAtopic Dermatitis and Vaccinia Network (ADVN )manyDonald Leungmany2761Flow cytometry, ELISA, ELISPOT, RT-PCR, Microarry gene expression, GenotypingPartially loaded in PPW

  • Study summary

  • Study schematic

  • Study download packages

  • Summary of records for download

  • Download folder of data

  • Links to external resources

  • Data sets - Demographics

  • ImmPort-calculated summary statistics

  • Data sets - Assessments

  • Assessment summaries and links to complete results sets

  • Diastolic Blood Pressure

  • Data sets Adverse events

  • ELISA and FCM

  • Results, protocols, reagents, biological samples

  • Download of FCM sample sets

  • Complete representation of a clinical trial in ImmPortAccess data through advanced query interface as well

  • Take-home messageImmPort has been tailored to support the needs of the immunology research communityComprehensive integrated resource for the capture, support and analysis of a wide range of basic, translational and clinical research dataCompliant with established and emerging data standards, e.g. MIAME, MIFlowCyt, Cell OntologyWork collaboratively with system users to develop and implement novel data processing and analysis methods

  • Human Immune PhenotypeDependent on:age, race gender, genetic backgrounddisease status, therapeutic and vaccine interventionsGenetic predispositionsSNP, CNV, HLA typeCellular componentsFCM, ELISPOT, CyTOFSerum antibodyELISA, HAISerum cytokine/chemokineELISA, CBA, MSAntigen receptor repertoireSequencing, spectrotypingGene expressionMicroarray, QPCR, RNASeq

  • UT SouthwesternDavid KarpMegan KongDiane XiangYu (Max) QianJie HuangNishanth MarthandanYoung Bun KimPaula GuidryDavid Dougall

    CollaboratorsKaren Kessler (Rho)Keith Boyce (ITN)Dave Parrish (ITN)Ignacio Sanz (Rochester)Michael Feolo (NCBI)Glenys Thomson (UC Berkeley)Steven G. E. Marsh (ANRI)Bjoern Peters (LIAI)Effie Petersdorf (FHCRC)Steve Mack (CHORI)DAIT-funded programs

    Supported by NIH N01AI40076Northrop GrummanCarl DahlkeVincent DesboroughJohn CampbellYue LiuPatrick DunnLiz ThompsonTom SmithJeff WiserMike Attasi

    AcknowledgmentsDedicated to Carl Dahlke In Memorium

    *******Allelic true of 4 and 6-digit level unless sequencing entire cDNAtrue of 8-digit level unless sequencing the entire locus

    Genotypic true of all platforms ******Allelic and genotypic ambiguity reduction results for every subject at each locus

    Note location of logic document and flow chart

    Sow the results for the example file

    ****Archive support for 5 DAIT-funded programs and 2 consortium projectsRequested to support completed clinical trial from Glaxo Smith KlineRequested to support immunology experiment data from the DMID-supported Centers of Excellence for Influenza Research and Surveillance

    *6 projects focused on the identification of genetic pre-dispositions to adverse responses to infection and variable responses to vaccination.Projects are completed and data is loaded in the investigators private project workspace, for the most part.Schedule for release into semi-public area in 2011.*Program investigating variation in immune responses in special human population subsets.All groups have loaded some data into ImmPort; will review in more detail later.**Browse through all of the data.Start at the study level with basic administrative and study design information.**Overall study design schematic with study arms, timeline and kinds of events represented.**Download capabilities.**Number of data records of various sorts available.Click here and download a folder with all of the information.**Download folder contents, mainly in the form of tab-delimited text files for easy incorporation into spreadsheets for further analysis.**Links to external resources**Blocks of study data sets**In addition to the primary data, ImmPort also calculates useful summary statistics. In this case, summary of demographics distributions broken down by study arms.**Results from physical exam assessments.**Again, summaries and individual assessment components.Select an individual assessment e.g. Wheal measurement**Provide composite as well as unit and value component results.**FCM and ELISA**Drill into further details about the results, samples, protocols and reagents used.**Provide option to download various packages of FCM data broken down by study Arm, Visits, and Staining Panel.Over 2 Gigabytes of FCM data from this one study.**Example of a complete representation of a clinical trial and its resulting data in ImmPort.In addition to the representation shown here for browsing, the data can be queries and filtered using any of the criteria shown.***I want to thank the dedicated BISC team at UT Southwestern and Northrop Grumman for all of their hard work developing the ImmPort system.Id also like to acknowledge the help we have received for several people from Rho, ITN and Inaki Sanz group at U. Rochester.And finally, Id like to dedicate my presentation to a friend and colleague, Carl Dahlke, who passed away last month from an unexpected illness.

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