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www.IEDB.org
Bjoern Peters
La Jolla Institute for Allergy and Immunology
Buenos Aires, Oct 31, 2012
Overview
1. Introduction to the IEDB
2. Application: 2009 Swine-origin influenza virus
3. IEDB 2012+
What is the IEDB? NIH-sponsored free online resource
1. Database: repository of all published
experimentally-derived epitope information • Infectious disease
• Allergy
• Autoimmunity
• Transplantion/alloantigens
– Over 14,000 curated articles and direct submissions
– Over 90,000 unique epitopes
– Over 500,000 assays
2. Analysis Resource: tools to predict and model
immune responses
IEDB
www.iedb.org
Literature curation Epitope discovery
contract submission
Data Sources and Structure
Assay-Centric Data Representation
• IEDB captures the actual experimental assays relating to
– T cell responses
– B cell responses
– MHC Ligand Elution
– MHC Binding
• This allows searching in a variety of different ways
– By Epitope
– By Epitope Source
– By Immune Response
– By Host Organism
– By Assay …
Example query: All TB epitopes
recognized by T cells restricted
by MHC class II in humans
Advanced query
Only MTB epitopes recognized in
chronically infected humans and
detectable without in vitro restimulation
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IEDB applications
Meta-Analyses
Prediction tool
development
IEDB Analysis Resource • Epitope prediction tools
– Machine learning algorithms that generalize the data
contained in the IEDB to predict new epitopes
• MHC class I & II binding and processing
• B cell epitope predictions
• Epitope analysis tools
– Conservancy analysis
– Population coverage
– Homology mapping
– Cluster analysis
Epitope Analysis Tools:
Add value to epitope datasets
Conservation of swine flu (S-OIV)
epitopes as an example
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Swine flu project
• Initiated in spring 2009
• High mortality estimates based on first affected
population (Mexico)
• Novel combination of Swine and human influenza
strains
• Lack of neutralizing antibodies
fear of a global deadly pandemic
Swine flu project
• Question: Are there targets of pre-existing immunity in S-OIV?
How different is the pandemic virus from recent seasonal flu
viruses for the immune system?
• Query IEDB for all epitopes from influenza A
• Assemble sequences from recently circulating influenza strains
(=in the past 20 years),
• Epitopes contained in recently circulating strains are likely
targets of pre-existing immune responses
• Examine conservation of epitopes with likely pre-existing
immunity in seasonal flu strains vs. pandemic flu
• Follow up experimentally
50 B cell epitopes from
recent seasonal
influenza strains
55 sequences of
pandemic influenza
(10 antigens in each)
What does X number of
conserved epitopes in S-OIV
mean? Comparison to
seasonal flu 2008
The Number of Epitopes Described in the
Literature in Pre-2007 Years and Conserved
in Specific Strains
Influenza Strains B Cell T Cell – CD8+ T Cell – CD4+
Seasonal 2008 16 68 87
2009/S-OIV 8 54 57
Analysis of Conservation in S-OIV of
Known (pre-existing) Influenza
Responses
Hypothesis: Significant levels of preexisting immunity might exist in
the general population against S-OIV.
Greenbaum et al, PNAS, 2009
Preexisting T Cell Immunity
Against S-OIV in the General
Population
Greenbaum et al, PNAS, 2009
Conclusions: Swine Flu epitope
conservation
• The conservancy tool predicted that pre-existing immunity
exists in the general population at the T cell (but less at
the B cell) level
• Experimentally measured T cell responses confirmed that
preexisting memory against S-OIV epitopes were similar
in magnitude compared to new seasonal influenza
Analysis tools available in the
IEDB-AR
• Conservancy analysis Analyze if epitopes are found
conserved across different protein sequences
• Population coverage Analyze how many T cell epitopes with
known HLA restriction will be recognized in a human population
based on HLA frequencies
• Homology mapping Analyze the structure of an epitope in its
source antigen based on homology mapping
• Cluster analysis Analyze how many epitopes in a set have
significant sequence homology
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Summary IEDB Introduction
+ S-OIV meta-analysis
• The IEDB catalogs all experiments characterizing
epitopes
• Multiple query mechanisms allow definition of
custom epitope sets
• IEDB epitope data is used to develop prediction
algorithms and perform Meta-Analysis
• IEDB Analysis tools help to examine existing sets of
epitopes and gain new knowledge
• Without the IEDB such meta-analysis would cost
much more time and effort 31
IEDB 2012+
• First funding period 2004 – 2011
• Renewal awarded for 7 more years
Update on priorities in the second funding
period
– Populating the IEDB
– Query enhancements
– Reporting enhancements
Populating the IEDB
PubMed Epitope
References
Over 21 Million 171,639
Relevant
References
29,559
Infectious Disease Allergy
Autoimmunity Transplantation
Cancer HIV
Others
Curation
Query Automatic
Abstract scans
Domain Classification
18,104
We finally caught up!
Curation from now on
• Reduced effort allows to cut expense and
refocus on other areas
• Implementation of biweekly update process
– data will appear faster
– You will be able to rely on the IEDB as a source of
current in addition to historical information
The IEDB 2012+:
Hierarchical queries using
ontologies
Example: Hierarchical query tree for
proteins
Queries for non-peptidic molecules
and diseases
Finders require replacing IEDB controlled
vocabularies with ontology classes
• Where available, re-use existing ontologies
• As necessary, contribute to building ontologies
• Benefits:
– Increase consistency in data curation
– Avoid duplicates
– Improve documentation to external users
– Enhance search capabilities
The IEDB 2012+:
Aggregate reporting using Immunome
Browser
Problem: Existing ways of displaying
immune epitope data have limitations
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Query: T cell
epitopes in TB
Solution: Immunome Browser
A web application, integrated into the IEDB
Maps epitopes onto antigens from a reference
genome – minimize redundancy, consistent use
of antigen names
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Mapping epitopes onto antigens
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M.bovine >gi|398979|A85B_MYCTU Antigen 85-B precursor
MTDVSRKIRAWGRRLMIGTAAAVVLPGLVGLAGGAATAGAFSRPGLPVEYLQVPSPSM
GRDIKVQFQSGGNNSPAVYLLDGLRAQDDYNGWDINTPAFEWYYQSGLSIVMPVGGQS
SFYSDWYSPACGKAGCQTYKWETFLTSELPQWLSANRAVKPTGSAAIGLSMAGSSAMI
LAAYHPQQFIYAGSLSALLDPSQGMGPSLIGLAMGDAGGYKAADMWGPSSDPAWERND
PTQQIPKLVANNTRLWVYCGNGTPNELGGANIPAEFLENFVRSSNLKFQDAYNAAGGH
NAVFNFPPNGTHSWEYWGAQLNAMKGDLQSSLGAG
Epitope #1: AEFLENFVRSSNLKFQDA from antigen “Antigen 85-B precursor“ of
M.bovis BCG strain
Epitope #2: VFNFPPNGTHSWEYWGAQ from antigen “alpha-antigen“ of
M.tuberculosis H37Rv strain
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Identification of 'antigenic regions' in TB
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IEDB Conclusions
• IEDB has established a versatile database
structure and curation processes to capture
diverse immune epitopes
• Literature curation is current in all categories
and new articles are typically curated within 4
weeks from entry in PubMed
• Focus of renewal period is on improving the
query and reporting mechanisms, coming online
in the next months
Acknowledgments La Jolla Institute for Allergy & Immunology
San Diego Supercomputer Center • Phil Bourne
• Julia Ponomarenko
Consultants • Laura Zarebski (Buenos Aires)
• David Nemazee (Scripps)
• Ralph Kubo (KKC)
• Chemical Entities of Biological Interest (ChEBI)
Science Applications International Corporation
CBS / UC team
La Jolla Institute for Allergy and Immunology
• non-profit research institute
• focused exclusively on immune system research
• 21 faculty (20 experimental, 1 bioinformatic)
• >100 postdoctoral employees
Always open positions for
bright + enthusiastic
students / postdocs /
visiting scholars
