Download 169) `Immune Epitope Database (IEDB) and its use of formal

Randi Vita, M.D.
Ontology Usage by the
Immune Epitope Database and Analysis Project
La Jolla Institute for Allergy & Immunology
Division of Vaccine Discovery
La Jolla, California
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What is an epitope?
The portion of a pathogen, allergen, or
autoantigen that the immune system
recognizes is the epitope
Antibodies and T cells
bind to epitopes to trigger
an immune response
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Why do epitopes matter?
Vaccine development
Allergy immunotherapy
Immunogenicity
Transplantation
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Antibody Epitopes
Antibodies typically bind
to discontinuous
residues of proteins
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T cells recognize epitopes (typically
peptides) presented by MHC Molecules
T cell
APC
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Nonpeptidic Epitopes
Antibodies and T cells also bind to lipids, metals,
carbohydrates, drugs, etc.
Example epitopes: penicillin, nickel, beryllium,
cardiolipin, alpha-Galc
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The Immune Epitope Database
Free online resource of experimentally-derived
epitope information
Scope
Allergy
Infectious diseases
Autoimmune diseases
Transplant/alloantigens
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IEDB Status
IEDB has >99% of all published epitope data
PubMed is queried every 2 weeks
New data is added every week
Goal is to have 80% of newly published data
publically available within 6 weeks
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The Immune Epitope Database
17,537 references
>1,000,000 assays
214,332 peptidic epitopes
2,379 nonpeptidic epitopes
584 T cell epitopes
1925 Antibody epitopes
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Data Structure
A database of experiments
OBI
Assay
Host
Immunization
Antibody or T cell
Antigen
Assay
Host
Immunization
Antibody or T cell
Antigen
Assay
Host
Immunization
Antibody or T cell
Antigen
Assay
Host
Immunization
Antibody or T cell
Antigen
Assay
Host
Immunization
Antibody or T cell
Antigen
Epitope
Reference
Epitope
Epitope
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Collaborations with existing resources
and ontologies
Ensures consistency and accuracy
Provides standardized nomenclature
Provides definitions, synonyms, and hierarchical
relationships for database terms
Makes curation easier
Enhances user experience
Facilitates interoperability
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Protein Resources
Amino acid sequence
Peptidic
Epitope
Protein source
Organism source
PKYVKQNTLKLAT
hemagglutinin HA1
GenBank/UniProt
GI:82032767—UniProt:P03452
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Organism Ontology
Amino acid sequence
Peptidic
Epitope
Protein source
Organism source
Human herpesvirus 5 (HHV-5)
NCBI
taxon:10359
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Chemical Ontology
Epitope structure
Non-peptidic
Epitope
Epitope source
Amoxicillin
ChEBI
CHEBI:2676
Organism source
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Disease Ontology
Host
Immunization
Immunogen
Process(es)
Disease
Peanut allergy
DO
DOID:4378
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Assay Ontology
Assay Type
Assay
T cells
MHC restriction
ELISA IL-2 release
OBI
OBI:1110152
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MHC Restriction Ontology
Assay Type
Assay
T cells
MHC restriction
HLA-DPA1*02:01/DPB1*01:01 protein complex
MRO
MRO_0001175
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Chemical Entities in IEDB
Peptidic epitopes
Modified peptides
Non-peptidic epitopes
Diseases caused by chemicals
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Chemical Entities in IEDB
Peptidic epitopes
Large amounts of data
Described by letters
Modified peptides
PubChem
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Chemical Entities in IEDB
Non-peptidic epitopes
ChEBI
Roles
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Chemical Entities in IEDB
Diseases involving chemicals
Establish links:
Disease Ontology → ChEBI
Example: penicillin allergy (DO:XXX) manifests in allergic
reaction to penicillin (CHEBI:17334)
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What the chemical informatics
community can do for immunology
Immunologist friendly hierarchies
Links back to biology
Query across resources
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Organism example in IEDB
NCBI hierarchy
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Organism example in IEDB
Immunologist friendly hierarchy
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Immunologist friendly chemical hierarchy
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Links back to biology
Immunologist groupings without obvious chemical relationships
Chlamydiae
Lipopolysaccharide ChEBI:16412
 3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid CHEBI:43577
 alpha-D-Kdo-(2->8)-alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-beta-D-GlcN4P-(1->6)-alpha-D-GlcN-1P ChEBI:61714
Shigella
Lipopolysaccharide ChEBI:16412
 alpha-L-Rhap-(1->2)-alpha-L-Rhap-(1->3)-[alpha-D-Glcp-(1->4)]-alpha-LRhap-(1->3)-beta-D-GlcpNAc-(1->2)-alpha-L-Rhap3Ac-(1->2)-alpha-LRhap-(1->3)-[alpha-D-Glcp-(1->4)]-alpha-L-Rhap-(1->3)-beta-DGlcpNAc,OCH2CH2NH2 CHEBI:78942
Autoantigens
 cardiolipin CHEBI:28494
 phosphatidylinositol CHEBI:28874
 beta-D-Gal-(1->3)-beta-D-GalNAc-(1->4)-beta-D-Gal-(1->4)-beta-D-Glc(1<->1')-Cer CHEBI:27938
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Query across resources
If more resources represent biological /
chemical information utilizing formal ontologies
(especially OBO foundry)
• Interoperability between data sources is
faciliated
• Queries across resources become possible.
Examples:
What are shared features of chemicals causing
allergic responses
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Thanks
ChEBI
Leidos
James Overton
Evan Bolton
IEDB Team
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