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1 Immunology Database and Analysis Portal ImmPort www.immport.org Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center 16 DEC 2010

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

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

1

Immunology Database and Analysis PortalImmPort

www.immport.org

Richard H. Scheuermann, Ph.D.Department of Pathology

U.T. Southwestern Medical Center

16 DEC 2010

Page 2: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 3: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Take-home messages

• ImmPort has been tailored to support the needs of the immunology research community

• Comprehensive integrated resource for the capture, support and analysis of a wide range of basic, translational and clinical research data

• Compliant with established and emerging data standards, e.g. MIAME, MIFlowCyt, Cell Ontology

• Work collaboratively with system users to develop and implement novel data processing and analysis methods

Page 4: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Built by

ImmunologistsBioinformaticiansComputational BiologistsBiostatisticiansProfessional Software Developers

for Immunologists

Tailored for immunology

Built by Immunologists for Immunologists

Page 5: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Vignettes

• HLA Region Genetics Consortium

– HLA typing ambiguity reduction pipeline

– HLA sequence feature definition and variant type analysis and visualization

– PyPop-based genetic analysis

• Novel methods and infrastructure for flow cytometry analysis – FLOCK

• Comprehensive support for clinical and translational research design and results data – Casale/ITN

Page 6: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

www.immport.org

Page 7: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Reference and research data

Page 8: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Visualization tools

Page 9: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Analysis tools

Page 10: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Workspaces

• Public– Reference data– Accessible without registration or log in

• “Semi-public”– Research data released after publication– Access to analytical tools– Registration and log in required for access– Accessible to all registered users

• Private– Pre-publication research data– Access controlled by P.I. (or P.M.)

• Collaborative– Controlled sharing of research data

Page 11: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Vignettes

• HLA Region Genetics Consortium

– HLA typing ambiguity reduction pipeline

– HLA sequence feature definition and variant type analysis and visualization

– PyPop-based genetic analysis

• Novel methods and infrastructure for flow cytometry analysis – FLOCK

• Comprehensive support for clinical and translational research design and results data – Casale/ITN

Page 12: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

12

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

Page 13: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Representative Sequence Features

Page 14: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

14

A*0201 - ‘CD8 binding’ &‘TCR binding’ SF

CD8 Binding

TC

R B

inding

Page 15: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Summary of SFs defined

1775 total

Page 16: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 17: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Publication

67F 70D

71R

86V

26F

37Y

30Y28D

67I 70D

71R

86G

26F

37F

30L28E

protective risk

Page 18: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

18

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

Page 19: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 20: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Ambiguity in HLA Typing Data

Page 21: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 22: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Outcome of HLA Ambiguity Reduction

Allelic Ambiguity Reduction

Genotypic Ambiguity Reduction

Page 23: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 24: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 25: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Vignettes

• HLA Region Genetics Consortium

– HLA typing ambiguity reduction pipeline

– HLA sequence feature definition and variant type analysis and visualization

– PyPop-based genetic analysis

• Novel methods and infrastructure for flow cytometry analysis – FLOCK

• Comprehensive support for clinical and translational research design and results data – Casale/ITN

Page 26: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Flow Cytometry Analysis

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

Page 27: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 28: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 29: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 30: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern
Page 31: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Population statistics

Page 32: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Summary Statistics

Page 33: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

B cell component of the Cell Ontology

http://www.obofoundry.org/

Page 34: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

FlowCAP

Page 35: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Vignettes

• HLA Region Genetics Consortium

– HLA typing ambiguity reduction pipeline

– HLA sequence feature definition and variant type analysis and visualization

– PyPop-based genetic analysis

• Novel methods and infrastructure for flow cytometry analysis – FLOCK

• Comprehensive support for clinical and translational research design and results data – Casale/ITN

Page 36: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

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

Page 37: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 38: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 39: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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

Page 40: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Study summary

Page 41: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Study schematic

Page 42: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Study download packages

Page 43: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Summary of records for download

Page 44: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Download folder of data

Page 45: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Links to external resources

Page 46: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Data sets - Demographics

Page 47: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

ImmPort-calculated summary statistics

Page 48: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Data sets - Assessments

Page 49: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Assessment summaries and links to complete

results sets

Page 50: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Diastolic Blood Pressure

Page 51: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Data sets – Adverse events

Page 52: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

ELISA and FCM

Page 53: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Results, protocols, reagents, biological samples

Page 54: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Download of FCM sample sets

Page 55: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Complete representation of a clinical trial in ImmPort

Access data through advanced query interface as well

Page 56: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

Take-home message

• ImmPort has been tailored to support the needs of the immunology research community

• Comprehensive integrated resource for the capture, support and analysis of a wide range of basic, translational and clinical research data

• Compliant with established and emerging data standards, e.g. MIAME, MIFlowCyt, Cell Ontology

• Work collaboratively with system users to develop and implement novel data processing and analysis methods

Page 57: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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, HAISerum antibodyELISA, HAI

Serum cytokine/chemokineELISA, CBA, MSSerum cytokine/chemokineELISA, CBA, MS

Antigen receptor repertoireSequencing, spectrotypingAntigen receptor repertoireSequencing, spectrotyping

Gene expressionMicroarray, QPCR, RNASeqGene expressionMicroarray, QPCR, RNASeq

Page 58: 1 Immunology Database and Analysis Portal ImmPort   Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern

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