1 Genetic and Human Phenotype Data Support in the Immunology Database and Analysis Portal ImmPort Richard H. Scheuermann,

1

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

http://www.immport.org/

http://www.niaid.nih.gov/default.htm

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

http://www.ImmPort.org/

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:


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


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


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


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




Special Pops


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


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


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


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


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


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,


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


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









Project Title InstitutePrinciple


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


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


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


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


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


HLA Region Genetics in Immune-Mediated Diseases Program





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








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


ADVN

Atopic Dermatitis and Vaccinia Network (ADVN ):





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


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


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


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,


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


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








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


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












ImmPort Genetic Analysis Tools

Haploview Implementation

Browse/Download Results

Ped File Generation

LD Select Implementation












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





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





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

[email protected]; 214-648-4115

mailto:[email protected]

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

Documents

1 Genetic and Human Phenotype Data Support in the Immunology Database and Analysis Portal ImmPort Richard H. Scheuermann,