Immunology Database and Analysis Portal ( ImmPort )

Immunology Database and Analysis Portal (ImmPort)

Richard H. Scheuermann, U.T. Southwestern

13DEC2010

Outline

Summary of projects supported by ImmPortSemi-public research data in ImmPort

Complete representation of clinical research design and results ITN Casale study example

Status of Special Pops data submissionData submission support

Support contacts Project Blueprints

FLOCK and FlowCAP poster

Projects Supported

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

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


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




HLA Genetics Consortium


HLA Region Genetics in Immune-Mediated Diseases Program



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

Special Pops


Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Program

Project Title InstitutionPrinciple


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











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

Consortium Projects







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


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

Semi-public completed study ITN Casale

ImmPort home page login

Semi-public workspace projects

Study summary

Study schematic

Additional study summary contents

Study objectives

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

Links to results

Diastolic Blood Pressure

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

Take home lessons

ImmPort is starting to accumulate a lot of interesting immunology research data

First completed project dataset 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

Clinical and translational research is very complex Representation of clinical and translational research is also

very complex, but ImmPort has developed a complete infrastructure to support this representation

Submission and loading of data into ImmPort is challenging Use BISC support services We still have more to do to make the data maximally

accessible and usable

Special Pops submission status

Current submission statusProject Projects Experiments Subjects Biosamples

Experiment Samples Total

Experiment Samples

Reagents Results

Project_ID=431 1 2 147 265 48263878 FCM; 948

ELISA? 218 GB

Project_ID=2 1 236 170 2333 9321 9321 70>9000 FCM

Project_ID=1860 1 29 522 4197 720 720 FCM ? >7.73 GB

Project_ID=1995 1 2 903 903 7524 7524 ELISA ?7524

ELISA

Project_ID=3 1 6 135 556 571531 ELISA; 205

Gene expression; 5479 FCM

106 pending

Project_ID=230; Project_ID=231 2 6 342 660 10001000 ELISA, PCR, FCM

159 ?

Project_ID=109; Project_ID=7; Project_ID=89

3 29 648 827 827333 ELISA; 266 FCM; 42 HLA

typing; 186 other? pending

Project_ID=9 1 48 235 2222 22231956 FCM; 267

Other? pending

Project_ID=129 1 2 2700 3000 ? ? ? pending

Project_ID = 593 1 * * * * * * *

Special Pops Totals 360 5802 14963 32156

Submission support

BISC contacts

PI Institution Primary Contact Secondary Contact

Dr. Lynn Hajjar University of Washington Patrick Dunn Nishanth Marthandan

Dr. Janko Nikoich-Zugich Oregon Health Science University Patrick Dunn David Dougall

Dr. Kathleen Sullivan The Children's Hospital of Philadelphia Jie Huang Patrick Dunn

Dr. Gundi Ertl The Wistar Institute, Philadelphia Young Kim Patrick Dunn

Dr. Jack Gorski The Blood Center of Southeastern Wisconsin Diane Xiang Patrick Dunn

Dr. Chris Larsen Emory University Yu Qian Patrick Dunn

Dr. Tom Moran Mt. Sinai School of Medicine Jie Huang Patrick Dunn

Dr. Ignacio Sanz University of Rochester Yu Qian Patrick Dunn

Dr. Linda Thompson Oklahoma Medical Research Foundation Patrick Dunn Jie HuangDr. Ruth MontgomeryDr. Erol Fikrig Yale David Dougall Patrick Dunn

BISC Contacts for Special Population

Don’t go it alone!!

[email protected]; 214-648-4115

mailto:[email protected]

Data Submission

Mechanistic assays Metadata – experiment, experiment sample, biological sample, subject,

reagent, protocol Results – 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

Clinical Data Submission

1. Study Design

Study design templates

2. Case Report Form Data Mapping of CRF data Load file generation Loading data into the database

3. Experiment Data Submission ImmPort experiment templates

Clinical Data Submission for ADVN

Data Submission TaskResponsible

Organization

Clinical Study Design Rho

CRF Data Mapping BISC

Load File Generation Rho

Load Data into Database BISC

Data Validation BISC + Rho

Experimental Data Rho (Lab Researcher)

Clinical Data Submission for ADVN

Data Submission TaskResponsible

Organization

Clinical Study Design Rho

CRF Data Mapping BISC

Load File Generation BISC

Load Data into Database BISC

Data Validation BISC + Rho

Experimental Data Rho (Lab Researcher)

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

Special Pops Summary

All groups have submitted some dataWe expect the data submission traffic to increase

significantly over the next 5 monthsTranslational research is complex making data

submission challengingTake advantage of BISC team supportBlueprints are a useful roadmap to keep track of

submission plans and status

FLOCK and FlowCAP

See poster

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

Karen Kessler (Rho)Keith Boyce (ITN)Dave Parrish (ITN)Ignacio Sanz (Rochester)Clinical Advisory BoardDAIT-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

Immunology Database and Analysis Portal ( ImmPort )