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Genetic and Human Phenotype Data Support in the Immunology Database and Analysis Portal
ImmPortwww.immport.org
Richard H. Scheuermann, Ph.D.Department of Pathology
U.T. Southwestern Medical Center
19 JAN 2011
Outline
• Summary of project data in ImmPort• First complete dataset available – ITN Casale• Collaborative ImmPort development projects
– HLA Genetics Consortium and HLA typing data
– PopGen and genetic analysis
– Special Pops and FCM analysis
• Data from previous PopGen projects• Data submission support
ImmPort Purpose and History
• NIH/NIAID/DAIT would like to:– maximize the return on the public investment in basic, translational and
clinical research
– allow 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 data
– Integrate these research data with extensive biological knowledge
– Support analysis of these integrated data
5+ DAIT-funded Programs
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Program
Population Genetics Analysis Program: Immunity to Vaccines/Infections Program
HLA Region Genetics in Immune-Mediated Diseases Program
Other Consortium Projects
Immune Modeling Centers
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Reagent Development for Toll-like and other Innate Immune Receptors
DMID-funded Centers of Excellence for Influenza Research and Surveillance
GlaxoSmithKline – COPD trial
Human Immune Phenotyping Centers
34 Projects, >100,000 subjects, terabytes of FCM, microarray, SNP genotype, ELISA, ELISPOT, etc. data
PopGen
Grants/Contracts/Projects:
Population Genetics Analysis Program: Immunity to Vaccines/Infections Program
Project Title Institute Principle
Investigator Objective Number of Subjects Mechanistic Assays Status
Immunity 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 PPW
Population 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.
2000
Sequencing , 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
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Special Pops
Grants/Contracts/Projects:
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Program
Project Title InstitutionPrinciple
Investigator ObjectiveNumber of
Subjects Mechanistic Assays Status
An Improved Influenza A Vaccine for Rapid Protection of the Elderly
The 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 Cytometry
Partially loaded in PPW
Protective Immunity in Transplant Recipients
Emory Transplant Center
Larsen, Christian, Ph.D.
To determine the effects of chronic immunosuppressive therapies on adaptive, innate and specific immunity
90ELISA, ELISPOT, Microarry, RT - PCR
Partially loaded in PPW
Kinetic analysis of immunologic repletion and influenza vaccine responsiveness
Children´s Hospital of Philadelphia
Sullivan, 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 responses
54ELISPOT, Sequencing, Flow Cytometry
Partially loaded in PPW
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations: TLRs in Innate Immunity and the Induction of Adaptive Immunity in the Neonate and Infant
University of Washington
Hajjar, 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) immunity
17 adults, 17 neonates
RT-PCR, ELISA, Flow Cytometry, Microarray
Partially loaded in PPW
Responses to Influenza Vaccination in Systemic Lupus
Oklahoma 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-PCR
Partially loaded in PPW
Immune function and Biodefense in Children, Elderly and Immunocompromised Populations
Oregon Health and Science University
Nikolich-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 PPW
Immune Response to Virus Infection During Pregnancy
Mt. Sinai School of Medicine
Moran, 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 vaccination
75Flow Cytometry, multiplex ELISA, RT-PCR
Partially loaded in PPW
Rochester Biodefense University of Rochester Sanz, Ignacio, M.D.To identify the specific immune defects that make immunocomprised populations specially susceptible at bioterrorists attack.
280 Flow CytometryPartially loaded
in PPW
Innate Immune Responsiveness in the Elderly and the Immunosuppressed
Yale School of Medicine
Montgomery, Ruth, M.D.,Erol Fikrig, MD
This 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, ELISA
Partially loaded in PPW
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Immune Modeling Centers
Grants/Contracts/Projects:
Immune Modeling Centers
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Project Title InstitutePrinciple
Investigator ObjectiveNumber of
Subjects Mechanistic Assay Status
Modeling Immunity for BiodefenseMount Sinai School of Medicine
Stuart C. Sealfon, M.D.
The main research goal of this project is to develop experimental data-based mathematical models of human myeloid dendritic cell signaling responses to viral infection.
N.A.Flow cytometry, ELISA, Luminex, qPCR
Partially loaded in PPW
Modeling Immunity for Biodefense Duke UniversityThomas Kepler, Ph.D.
Development of computational tools for application in the rational design of vaccine adjuvants.
~500 mice
Flow cytometry, qPCR, ELISA, Luminex, Microarray Gene Expression, Immunohistochemistry
Partially loaded in PPW
Modeling Infection by and the Immune Responses to Pulmonary Pathogens
University of PittsburghPenelope A. Morel, M.D.
Modeling Immunity for Biodefense: Modeling Infection by and Immune Responses to Pulmonary Pathogens.
N.A.
Flow cytometry, qPCR, ELISPOT, ELISA, Luminex, Microarray Gene Expression, Immunohistochemistry
Partially loaded in PPW
Modeling Immunity for Biodefense University of Rochester Hulin Wu, Ph.D.
To develop comprehensive, computational models of the human immune response to unmodified and genetically engineered influenza A.
N.A.Flow cytometry, FLORISPOT, qPCR, ELISPOT, Hemaglutination assay
Partially loaded in PPW
Modeling Immunity to Enteric Pathogens (MIEP)
Virginia Bioinformatics Institute (Virginia Tech)
Josep Bassaganya-Riera, Ph.D.
N.A. N.A. N.A.Nothing loaded
yet
HLA Genetics Consortium
Grants/Contracts/Projects:
HLA Region Genetics in Immune-Mediated Diseases Program
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Project Title InstitutePrinciple
Investigator ObjectiveNumber of
Subjects Mechanistic Assays Status
HLA Region Genetics and SLE in U.S. Black Women
Boston U-Slone Epidemiology
Rosenberg, Lynn
To survey the HLA region for genetic associations with SLE in 400 African American women with SLE and 800 matched African-American controls from the BWHS
1200 Microarray, Genotype, Sequencing
Nothing loaded yet
HLA Region Genetics in Immune Mediated Disease: HLA/KIR Region Genetics in Pediatric Arthritis
Cincinnati Children´s Hospital
Glass, DavidTo construct high throughput SNP maps in a family based Juvenile Rheumatoid Arthritis study.
900 families
HLA genotyping, SNP genotyping, Sequencing, Wide Genome Association,
Nothing loaded yet
Epigenomics of Hematopoietic Cell Transplantation
Fred Hutchinson Cancer Research Center
Petersdorf, EffieTo define the genetic barriers to successful allogeneic hematopoietic cell transplantation (HCT).
15,548 HLA geneotypingPartially
loaded in PPW
The Role of HLA and KIR in Rheumatoid Arthritis and Crohns Disease
Children´s Hospital Oakland Research Institute (CHORI)
Erlich, Henry
To carry out case/control association analyses for Crohn's Disease and Rheumatoid Arthritis using our high resolution HLA and KIR(Killer Immunoglobulin-like Receptors) genotyping methods.
94 GenotypingPartially
loaded in PPW
Molecular Genetics of HLA and DiseaseUniversity of California, San Francisco
Hauser, Steve
To identify and characterize the complete repertoire of genes encoded in the MHC region that predispose and/or modulate the expression of autoimmune disease.
14,700 SNP genotyping, SequencingNothing loaded
yet
Consortium Projects
Grants/Contracts/Projects:
Other Consortium Projects
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Project Title InstitutePrinciple
Investigator ObjectiveNumber of
Subjects Mechanistic Assay Status
Allergen immunotherapy Co-administered with Omalizumab shared to Semi-Public Workspace (SPW) Project
Immune Tolerance Network Group (ITN)
Thomas Casale
To 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.
159 Flow cytometry, ELISACompletely
available in SPW
Atopic Dermatitis and Vaccinia Network (ADVN ) many Donald Leung many 2761
Flow cytometry, ELISA, ELISPOT, RT-PCR, Microarry gene expression, Genotyping
Partially loaded in PPW
ADVN
Atopic Dermatitis and Vaccinia Network (ADVN ):
Other Consortium Projects
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Project Title InstitutePrinciple
InvestigatorObjective
Number of Subjects
Mechanistic Assay Status
Immune Response to Varicella Vaccination in Subjects with Atopic Dermatitis Compared to Nonatopic Controls (Varicella)
Children’s Hospital, Boston
Lynda Schneider, M.D.
To determine if children with AD have VZV-specific cell mediated immune (CMI) responses to varicella vaccination that differ from those of nonatopic controls
60 ELISA, ELISPOT, Flow Cytometry
Completely loaded in PPW
Responses to Immunization with Keyhole Limpet Hemocyanin (KLH)
National Jewish Medical and Research Center
Henry Milgrom, M.D.
To determine whether two administrations of KLH by the scarification route (15 jabs, 20 mg/mL) induce an anti-KLH IgG antibody response to KLH in nonatopic subjects
25 ELISACompletely loaded
in PPW
Analysis and Correlation of Cathelicidin Expression in Skin andSaliva of Subjects with Atopic Dermatitis and Psoriasis (CATH 02)
University of. California, San Diego
Richard Gallo, M.D., Ph.D.
To measure the local and systemic expression of cathelicidin (hCAP18/LL-37) in subjectswith ADEH-, ADEH+, psoriasis, and in non-atopic controls
80 ELISACompletely loaded
in PPW
Analysis of the Response of Subjects with Atopic Dermatitis to Oral Vitamin D3 by Measurement of Antimicrobial Peptide Expression in Skin and Saliva (CATH 03)
University of. California, San Diego
Richard Gallo, M.D., Ph.D.
To examine the effect of oral administration of Vitamin D3 on AMP (hCAP18/LL-37, HBD3) expression in AD subjects' skin as compared to change in AMP expression in lesional and non-lesional skin of subjects who receive the Vitamin D3 placebo.
80 RT-PCR, ELISACompletely loaded
in PPW
Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus ( AMP 01)
National Jewish HealthDonald Leung, M.D., Ph.D.
Recent studies have demonstrated that the T-Helper 2 cell (Th2) phenotype of AD skin suppresses antimicrobial peptides (AMP).
296 RT-PCR, Gene expression, Microarray
Completely loaded in PPW
Risk Factors in Atopic Dermatitis for the Development of Eczema Herpeticum (ADEH)
University of Bonn, Germany
Thomas Bieber, M.D., Ph.D.
Phenotypical, qualitative, and quantitative analysis of myeloid and plasmacytoid DCs of the different subgroups
240 Flow Cytometry, ELISA, ELISPOT, RT- PCR
Completely loaded in PPW
A study of the Systemic and Cutaneous Immune Responses to Yellow Fever Vaccination in Atopic Dermatitis Subjects (Yellow Fever)
Oregon Health Sciences University
Jon Hanifin, M.D.To gain greater insight into the immunological parameters that distinguish AD subjects from controls.
80 RT-PCR, ELISA, Radioimmunoassay,
Partially loaded in PPW
Genetics of Atopic Dermatitis – Eczema Herpeticum (Genetics)
University of RochesterLisa A. Beck, M.D.
To identify candidate genes relevant in AD subjects with a history of EH (ADEH+) and to characterize the frequency of minor allele variants in candidate genes according to African American and Caucasian race.
900 Genotyping, Expression profiling
Completely loaded in PPW
ADVN Biomarker Registry Study (Biomarker)
University of RochesterSusan Lieff, Ph.D.;Lisa A. Beck, M.D.
To facilitate ADVN clinical research designed to reduce the risk of eczema vaccinatum (EV), a complication of vaccinia immunization that occurs in patients with AD
1000 ELISAPartially loaded in
PPW
Human Immune Phenotype
Dependent on:age, race gender, genetic background
disease status, therapeutic and vaccine interventions
Genetic predispositionsSNP, CNV, HLA typeGenetic predispositionsSNP, CNV, HLA type
Cellular componentsFCM, ELISPOT, CyTOFCellular componentsFCM, ELISPOT, CyTOF
Serum antibodyELISA, HAI, and neutraliz.Serum antibodyELISA, HAI, and neutraliz.
Serum cytokine/chemokineELISA, CBA, MSSerum cytokine/chemokineELISA, CBA, MS
Antigen receptor repertoireSequencing, spectrotypingAntigen receptor repertoireSequencing, spectrotyping
Gene expressionMicroarray, QPCR, RNASeqGene expressionMicroarray, QPCR, RNASeq
Complete representation of ITN Casale
Complete support for ITN Casale
Grants/Contracts/Projects:
Other Consortium Projects
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
Project Title InstitutePrinciple
Investigator ObjectiveNumber of
Subjects Mechanistic Assay Status
Allergen immunotherapy Co-administered with Omalizumab shared to Semi-Public Workspace (SPW) Project
Immune Tolerance Network Group (ITN)
Thomas Casale
To 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.
159 Flow cytometry, ELISACompletely
available in SPW
Atopic Dermatitis and Vaccinia Network (ADVN ) many Donald Leung many 2761
Flow cytometry, ELISA, ELISPOT, RT-PCR, Microarry gene expression, Genotyping
Partially loaded in PPW
ImmPort home page login
Semi-public workspace projects
Study summary
Study schematic
Additional study summary contents
Study endpoints
Study download packages
Summary of records for download
Download folder of data
Links to external resources
ClinicalTrials.gov record
Data sets - Demographics
ImmPort-calculated summary statistics
Data sets - Assessments
Assessment summaries and links to complete
results sets
Assessment results details - Wheal
Data sets – Adverse events
Adverse events broken down by study arm
Data sets – Lab tests
Lab test summaries and links to complete results sets
Hematocrit
Data sets – Mechanistic assays
ELISA and FCM
Experiment samples
Results, protocols, reagents, biological samples
Download of FCM sample sets
Complete representation of a clinical trial in ImmPort
Access data through advanced query interface as well
Collaborative ImmPort Development Projects
• HLA Region Genetics Consortium
– HLA typing ambiguity reduction pipeline
– HLA sequence feature definition and variant type analysis and visualization
– PyPop-based genetic analysis
• Population Genetics Program
– Haploview implementation
– Ped file generation
– LD Select implementation
• Special Populations Program
– Novel methods and infrastructure for flow cytometry analysis – FLOCK
41
Summary of SFVT approach
• Traditional HLA allele association analysis treats entire allele as a single unit and does not capture the structural relationships between alleles
• Sequence 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 SF
– Examine the association between every sequence feature variant type and disease or other phenotype
Representative Sequence Features
43
A*0201 - ‘CD8 binding’ &‘TCR binding’ SF
CD8 Binding
TC
R B
inding
Summary of SFs defined
1775 total
Variant Types for Hsa_HLA-DRB1_beta-strand 2_peptide antigen binding
Publication
67F 70D
71R
86V
26F
37Y
30Y28D
67I 70D
71R
86G
26F
37F
30L28E
protective risk
47
ImmPort HLA SFVT Workflow
Table of subject vs. HLA 4-digit typing data Table of subject vs. SFVT feature vector
Table of p-values, adj. p-values, odds ratio, confidence intervals
CD8 Binding
TC
R B
inding
HLA Typing Platforms and Ambiguity
• HLA Typing Platforms– SSOP – single-stranded oligonucleotide probe– SSP – sequence-specific priming– SBT – sequence-based typing– SSCP – single-stranded conformation polymorphism
• Allelic Ambiguity– Typing methodology cannot distinguish between sets of
alleles– Polymorphisms 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/primers
• Genotypic Ambiguity– Inability to determine phase in heterozygous samples
Ambiguity in HLA Typing Data
Allelic Ambiguity Reduction
Eliminate others
Eliminate others
Are any of the alleles reg-CWD?
Are any of the alleles reg-CWD?
Elimination of less-probable alleles by CWD statusReduction of multiple alleles to G- or P-codes
yes
no
Eliminate others
Eliminate others
Are any of the alleles
CWD?
Are any of the alleles
CWD?
yes
no
Eliminate others
Eliminate others
Are any of the alleles reg-Rare?
Are any of the alleles reg-Rare?
yes
Combine to G-code
Combine to G-code
Do any alleles belong to a common G-
code?
Do any alleles belong to a common G-
code?
yes
no
Combine to P-code
Combine to P-code
Do any alleles or G-codes belong to a common P-
code?
Do any alleles or G-codes belong to a common P-
code?
yes
Eliminate rare alleles
Eliminate rare alleles
Do the alleles contain any
G- or P-codes?
Do the alleles contain any
G- or P-codes?
yes
no
Outcome of HLA Ambiguity Reduction
Allelic Ambiguity Reduction
Genotypic Ambiguity Reduction
ImmPort HLA Tools
Ambiguity Reduction Output
Collaborative ImmPort Development Projects
• HLA Region Genetics Consortium
– HLA typing ambiguity reduction pipeline
– HLA sequence feature definition and variant type analysis and visualization
– PyPop-based genetic analysis
• Population Genetics Program
– Haploview implementation
– Ped file generation
– LD Select implementation
• Special Populations Program
– Novel methods and infrastructure for flow cytometry analysis – FLOCK
ImmPort Genetic Analysis Tools
Haploview Implementation
Browse/Download Results
Ped File Generation
LD Select Implementation
Collaborative ImmPort Development Projects
• HLA Region Genetics Consortium
– HLA typing ambiguity reduction pipeline
– HLA sequence feature definition and variant type analysis and visualization
– PyPop-based genetic analysis
• Population Genetics Program
– Haploview implementation
– Ped file generation
– LD Select implementation
• Special Populations Program
– Novel methods and infrastructure for flow cytometry analysis – FLOCK
Traditional Flow Cytometry Analysis
•Subjective
•Time-consuming
•Doesn’t handle overlapping distributions well
•Sensitive to slight difference in fluorescence intensity distributions between samples
•Requires at least one 2D plot that clearly segregates populations in question
Goal - group together cells with similar characteristics
Traditional approach - manual gating 2D at a time
FLOCK
FLOCK is an algorithmic application for the identification of unique cell populations in multi-dimensional flow cytometry data
N1-3
UM1-2
UM3-4PB GSM
GNSM
DNM
CD27
IgD
A
FLOCK in ImmPort
2D Plot Overview
Population Plots
Cross Sample Plots
Population Statistics
FlowCAP
FlowCAP-I Data SetsDataset # Samples # Events # Colors Analyte-Reporter Provider
GvHD 12 14,000 4 CD4-FITC;CD8b-PE; CD8-APC;CD3-PerCP
BCCRC & TreeStar
DLBCL 30 5,000 3 CD5-FITC;CD19-PE; CD3-Cy5
BCCRC
HSCT 30 10,000 4 CD45.2-APC;CD45.1-FITC;Ly65/Mac1-PE;Dead cells-PI
BCCRC
WNV 13 100,000 6 CD3-PECy5; CD4-PECy7;CD8-AF700;IFN-PEA;IL17-APC;Free amine-CFSE
McMaster
ND 30 17,000 10 CD56-Q605;CD8-AF700;CD45-PECy5;CD3/CD14-PECy7;Proprietary-FITC, PerCPCy5, PacificBlue, PacificOrange, APC, PE
Amgen
FlowCAP-I Results
Automatically Predict Cluster Membership of Each Event (Cell)
POPGEN SUBMISSION STATUS
PopGen
Grants/Contracts/Projects:
Population Genetics Analysis Program: Immunity to Vaccines/Infections Program
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
PI Name PI Organization Project Title Keywords
Data Availability
Date-Final Public
Release
Amount of Data Available
Total Number
of Subjects
Total # of Subjects
Characteristics Collected
Total Number of Result Files or Records
Total Amount of Data
Gregory A. Poland, M.D . Mayo Clinic Immunity to Vaccinia Virus
Infection
smallpox, immunogentics,
genetic association, elispot, elisa,
cytokines, neutralizing antibody
9/30/2011 1063 4
ELISPOT 1275650 MB (BISC
will load additional 22 GB of GE,
Flow, GT data)
HLA Typing 1071Viral
Neutralization Assay
1071
Genotyping other 1056
Mark Loeb, Ph.D.
McMaster University
Population Genetics Program on West Nile Virus Project
West-Nile Virus, Population genetics,
genotyping, polymorphism,
candidate genes
9/30/2011 1659 9 Genotyping Illumina 1699
1.37 GB (BISC will load
additional 27 GB of GT data)
Jeffrey Gulcher,
M.D., Ph.D. deCODE Genetics
Immunity to Vaccines/Infections Immune Response Polymorphisms: Smallpox, Tuberculosis, Influenza and Common Encapsulated Bacteria Infections
smallpox, polymorphism 9/30/2011 0 0 0 0
300 MB (BISC is building
summarized data sets with
deCode)
PopGen
Grants/Contracts/Projects:
Population Genetics Analysis Program: Immunity to Vaccines/Infections Program
ImmPort Research Data | My Work Bench
Browse Data/ ImmPort Research Data/ ImmPort Supported Programs
PI Name PI Organization Project Title Keywords
Data Availability
Date-Final Public
Release
Amount of Data Available
Total Number
of Subjects
Total # of Subjects
Characteristics Collected
Total Number of Result Files or Records
Total Amount of Data
Diane Wagener,
Ph.D.RTI International
Immune Response Polymorphisms: Typhoid/Cholera Vaccines
Polymorphism, typhoid, cholera
9/30/2011 2097 4
Mass Spectrometry 3537
0.5 GB
ELISA 6001Genotyping
other 2085DIGE Assay 4386Vibriocidal
Assay 2000Multiplex Bead
Assay 7394Christopher B. Wilson,
M.D. ,Debbie
Nickerson, Ph.D.
University of Washington
Genetic Risk for Smallpox Vaccine Related to Myocarditis
smallpox vaccine, myopericarditis, risk,
genetic9/30/2011 413 4
HLA Typing 312
63 GB
Genotyping other 331
Genotyping Illumina 76
Richard Kaslow, M.D.
University of Alabama at
Birmingham, Birmingham AL
Genetic Factors and Immune Response to Anthrax Vaccine Anthrax, variation 9/30/2011 2641 5
HLA Typing 949
0.8 GBGenotyping
other 1365
ELISA 375
SUBMISSION SUPPORT
User Support
PI Institution Scientific Contact Technical Contact
Dr. Gregory Poland Mayo Clinic Paula Guidry Patrick Dunn
Dr. Mark Loeb McMaster University Nishanth Marthandan Patrick DunnDr. Richard Kaslow/Dr. Robert Kimberly University of Alabama at Birmingham Jie Huang Patrick DunnDr. Deborah Nickerson/ Dr. Chris Carlson University of Washington Nishanth Marthandan Patrick Dunn
Dr. Pardis Sabeti Broad Institute Jie Huang Patrick Dunn
BISC Contacts for PopGen
richard.scheuermann@utsouthwestern.edu; 214-648-4115
Data Submission
• Mechanistic assays (online or hard drive)– Metadata (.xls or .xml) – experiment, experiment
sample, biological sample, subject, reagent, protocol
– Results (native results formats) – FCM, HLA typing, microarray or RT-PCR for expression, ELISA for serum antibody or cytokine, ELISPOT, SNP genotyping
• Clinical data– Study design timeline and clinical phenotypes from
CRFs collected separately
– No PHI
Metadata
subjectAnimal
Subject User-Defined ID*Species name*Subject Treatment Protocol User-Defined ID*Subject Treatment Protocol ImmPort Accession*
Enrollment AgeAge UnitGenderStrain NameStrain CharacteristicsFamily Pedigree IDSubject's Pedigree IDFather's Pedigree IDMother's Pedigree IDAffection StatusAffection Phenotypetreatment agent 1 nametreatment agent 1 concentrationtreatment agent 1 volumetreatment agent 1 weighttreatment 1 durationtreatment 1 temperature
bioSample
Biological Sample User-Defined ID*Biological Sample Type*Biological Sample Protocol User-Defined ID*Biological Sample Protocol ImmPort Accession*
Biological Sample NameBiological Sample DescriptionBiological Sample sub-typeSource Biological Sample User-Defined IDSource Biological Sample ImmPort AccessionSource Subject User-Defined IDSource Subject ImmPort AccessionPooled SampleBiological Sample PurityBiological Sample ConcentrationBiological Sample VolumeBiological Sample Weighttreatment agent 1 nametreatment agent 1 concentrationtreatment agent 1 volumetreatment agent 1 weighttreatment 1 timetreatment 1 temperature
experiment
Experiment User-Defined ID*Experiment Type*Measurement technique*Protocol User-Defined ID*Protocol ImmPort Accession*
Experiment NameDescriptionHypothesisRationaleKeywordsQuality Control MeasuresExperimentersLinks to PublicationsConstantsConditional VariablesResponding Variables
experimentSample
GE or GT or FCM or Other Experiment Sample User-Defined ID*Experiment User-Defined ID*Experiment ImmPort Accession*Protocol User-Defined ID*Protocol ImmPort AccessionReagent User-Defined ID*Reagent ImmPort Accession*
Experiment Sample NameExperiment Sample DescriptionResult File or Folder NameReplicate Group IDBiological Sample User-Defined IDBiological Sample ImmPort Accession
reagent
Array Reagent User-Defined ID*Array Platform Name*Manufacturer*Catalog Number*
Array Platform DescriptionArray Platform Annotation File NameLot NumberContactWeb Link
Suggested Flow of Filling Templates
ImmPort Data Submission Fields and Relations
protocol
Protocol User-Defined ID*Protocol File Name*
Blueprints
• We have started to use “study blueprints” to help coordinate data submission.
• Summarizes overall structural relationships among data components.
• Helps projects teams keep track of data for submission.
• Helps BISC team ensure that the correct links between data components are in place.
• Helps DAIT program officers keep track of submission status.
Blueprints
• Initial drafts prepared by BISC team based on project documentation – proposals, SOWs, study protocols
• Need to be reviewed, revised and returned by project personnel.
• Blueprints should be considered to be living documents subject to revision.
High-level relationships
Project description
Specific project
Study description
Genotyping experiment
FCM experiment
Summary
• ImmPort is starting to accumulate a lot of interesting immunology research data
• First completed project dataset (ITN Casale) made available in semi-public workspace in Oct 2010
• All of this data is now readily accessible by both the immunology research community and the study team itself
• BISC team available to provide submission support• Request
– For previous projects, allow BISC team access to PPW to validate accuracy and consistency data and representations before migration to semi-public workspace
– For new/renewed projects, provide proposals, protocols, SOW and/or other documentation for blueprint drafting
– Review blueprints when provided– Suggestion for future ImmPort enhancements
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 N01AI40076
Northrop GrummanCarl DahlkeVincent DesboroughJohn CampbellYue LiuPatrick DunnLiz ThompsonTom SmithJeff WiserMike Attasi
Acknowledgments
Dedicated to Carl Dahlke In Memorium
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