IEDB Overview. Bjoern Peters, Ph.D. Associate Professor IEDB Co-Principal Investigator

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1 IEDB Overview Bjoern Peters, Ph.D. Associate Professor IEDB Co-Principal Investigator 1

2 The Immune Epitope Database Free online resource of experimentally-derived epitope information T T B Allergens APC APC Infectious diseases Autoimmune diseases MHC Binding MHC Ligand Elution T Cell Response B Cell Response Transplant/alloantigens Over 18,000 curated articles + direct submissions 250,000 unique epitopes Almost 1.2 million assays 2

3 An Assay-centric, Context Dependent View Scientists have different definitions for epitopes IEDB captures the actual experimental assays in which epitopes were determined and characterized Users can search for epitopes based on these characteristics 3

4 Consistent Data Entry Requires Well Defined Data Structure Epitope Context Structure Source Immunization Assay Name 74A Chemical Type Peptide/Protein Sequence CLTEYILWV Domain / Region Defined Epitope Species Vaccinia virus Ankara Strain Ankara (MVA) Antigen putative 21.7k protein Antigen Accession Antigen Positions Immunized Species Homo sapiens Immunogen Type Source Species Administration Scarification Antigen Type Epitope Assay Type ELISPOT Response Measured Cytokine Release-IFN-g MHC Allele HLA-A*0201 4

5 epitope source (material entity) organism protein protein complex NCBI taxonomy UniProt Data structure has part epitope structure (material entity) peptide discontinuous protein residues carbohydrate is about ChEBI reference (document) journal article author submission IAO has participant immune recognition assay (process) B cell response T cell response MHC binding OBI, GO preceded by immunization (process) Natural Infection Exposure w/o disease Administered Immunization DO / IDO OBI 5

6 Metrics: Content Completion of historic curation 1,500,000 assays 381,000 epitopes 18,500 papers 300 data submissions 6

7 IEDB 3.0 Major redesign of query interface based on community feedback Focus on making common requests easy IEDB 3.0 replaced IEDB 2.13 in February 2015 as the main website We appreciate your feedback as we continue to enhance the IEDB! 7

8 Latest home page & search interface 8

9 Example Query: T cell epitopes recognized in Timothy grass allergic humans

10 Ontologies enable aggregation of results

11 Epitopes: specific molecules (here:peptides) tested

12 Assays: Experiments in which epitope was tested 12

13 References: Source of information Submission 13

14 Antigens: Identifying protein source of epitopes (isoforms)

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17 Recuration Efforts Papers curated early in the project are recurated to conform to new rules Further targeted revisions to Improve data consistency and uniformity based on data validation checks Populate newer data fields that did nor exist when the reference was originally curated The overall result will be increased accuracy and consistency of the data 17

18 The Submission Community Currently there are over 10 epitope discovery contracts and grants 10 contracts for infectious disease B and T cell epitopes Other grants submit allergy epitopes There have been 24 epitope discovery contracts previously Data submission metrics: 300 submissions 335,2111 total epitopes Submitted data currently comprises 25% of epitopes in the IEDB Data deposition is open to the general research community on a case-by-case basis 18

19 Meta-Analysis of Immune Epitope Data Inventory of current epitope knowledge T versus B, Chemical type, Host, Disease states, Conservancy and other variables Goals Facilitate use, identify gaps, engage community (experts) Increased data quality and confirms inclusion of critical data in the IEDB Influenza: Bui et al, PNAS 2007; Greenbaum PNAS 2009 TB: Blythe et al, Immunome Res 2007; Ernst et al. Tuberculosis 2007 Botulinum/Anthrax toxins: Zarebski et al, Expert Rev 2008 Malaria: Vaughan et al, Parasite Immunol 2009 Poxviruses: Moutaftsi et al, Future Microbiology, 2010 Flaviviruses: Vaughan et al, Viral Immunology 2010 Allergy: Vaughan et al, J Allergy 2011 HCV: Kim et al, PLoS One 2012 Myasthenia gravis: Vaughan et al, Autoimmune Dis Diabetes: Vaughan et al, Immunome Res 2013 Pertussis: Vaughan et al, Hum Immunol 2014 Multiple Sclerosis: Vaughan et al J Neuroimmunol 2014 Ebolavirus: Ponomarenko et al, PLoS Current Outbreaks, 2014 Zikavirus: Xu et al, PLoS Currents, more published 19

20 Promote Awareness of IEDB Data and Tools Present 4 exhibit booths per year Organize annual user workshop Perform at least 1 metaanalyses per year Publish IEDB related papers Expand help with video and written tutorials and integration of field-level help linked to ontology 20

21 Newest addition: Focus on TCR/BCR receptor data IEDB always contained epitope specific antibody and TCR data, but this was largely limited to data from crystal structures Advent of sequencing of receptor repertoires led to re-design of what should be captured for receptors New data structure includes: Receptor and chain types (e.g: alpha beta TCR) Full receptor sequence CDR1, CRDR2, CDR3 sequences Gene usage Captured for all newly curated data, and being re-curated for previously curated data 21

22 Receptor Search Interface will soon be added 22

23 And a new Receptor Results Tab 23

24 Already available: Receptor Downloads Download page 24

25 Our goals for this user workshop We want your input to make the IEDB better: Learn about real-life applications for the IEDB Identify and prioritize problems with the user interface, documentation, functionality etc. We want to enable you to get the most out of the IEDB: The primary IEDB success metric is usage Best compliment for our program is if IEDB data & tools help in your research (citations) 25

26 How the IEDB Can Help You! Experimental data Sequences Organisms IEDB Epitope Database Known epitopes Antigens MHC alleles Epitopes Other data Analysis Resource Epitope Prediction tools Epitope Analysis tools Predicted epitopes Analysis of epitopes 26