1. Immune Epitope Database assays

2. Standard immune epitope definition Classical (textbook) definition: An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells; a molecular region on the surface of an antigen capable of eliciting an immune response.  We want to store information about all aspects of epitopes in the IEDB

3. IEDB www.iedb.org Literature curation Epitope discovery contract submission Populating the IEDB

4. Process for categorization and curation of epitope references Wang et al, BMC Bioinformatics, 2007

5. Main Classes Journal articles Total RelevantOutstanding % Processed Infectious Disease 8,65139598.9 Allergy7683898.3 Autoimmunity3,8892,85847.5 Transplant6055823.8 Total13,9133,87380.4 Literature Curation Status  On track to be complete by end of this year

6. journal article reference (document) B cell response has part High level database structure is about T cell response author submission epitope structure (material entity) peptide discontinuous protein residues carbohydrate epitope source (material entity) organism protein protein complex immune recognition assay (process) MHC binding has participant Natural Infection Administered Immunization immunization (process) preceded by Vita et al, NAR, 2009

7. High level assay types

8. T cell assay example: IFN-g ELISA ELISA =def: an assay where an enzyme linked antibody is used to detect a plate bound material in a liquid (the evaluant) utilizing a chemiluminescent reaction. The detected signal is proxy for the concentration of an analyte in the evaluant. (this is actually not general enough; some ELISA formats are not detecting an analyte but e.g. cross-blocking) ELISA IFN-gamma assay =def: ELISA and analyte is IFN-gamma T cell epitope ELISA IFN-g assay =def: IFN-gamma ELISA and measurement datum is about some ‘epitope specific IFN-gamma release by T cells’ epitope specific IFN-gamma release by T cells =def: 'interferon-gamma production (GO_0032609)' and ('process is result of' some 'MHC:epitope complex binding to TCR')  Even the simplest assay we have requires implicitly that multiple controls are analyzed, and the results compared, which looks a lot like a study design.

9. T APC T No peptideWith peptide With IFNg antibody Without IFNg antibody

10. QTT 1 – epitope specific GO processes Excel spreadsheet that autoconverts to OWL via MappingMaster tool 51 of these Working with Martin (creater of MM) to fix bugs Imported GO processes into OBI Maintained in OBI, but should be IO

11. Assay techniques Created general assays in OBI

12. QTT 2 – T cell epitope assays Excel spreadsheet that autoconverts to OWL via MappingMaster tool 51 of these Working with Martin (creater of MM) to fix bugs Maintained in OBI, but should be IO

13. Complex ‘assays’: Assessing impact of epitope specific intervention on clinical findings Two groups of NOD mice that are model for diabetes; administer insulin epitope to one group; compare histology of pancreas after two weeks to assess disease course  For us still one ‘assay’ as we get a single datum out for the efficacy of that epitope intervention  For others this is clearly a study design Other complex assays: reduction of symptoms after treatment as a result of epitope specific T cells exacerbation of symptoms after treatment as a result of epitope specific T cells reduction of the presence of infectious agent as a result of epitope specific T cells reduction of the presence of tumor tissue as a result of epitope specific T cells survival as a result of epitope specific T cells

14. Past Approach (Vancouver 2010) Use study design instead of assay for the complex cases. Problem1: Is it clear that IFN-g assay is really an assay if it has internal controls? Problem2: A T cell epitope ELISA IFN-g assay could also be run outside of an investigation, but study design is reserved for that. Problem3: There are plenty of ‘assays’ right now e.g. microarray experiments, the Edingburgh handedness assay etc. that are just as complex as the above.  We could not identify criteria that delineate ‘assay’ and ‘study design execution’ based on complexity

15. Proposal Make ‘experiment’ an alternative term for ‘assay’ Allow for complex assays. This would be done by specifying more precisely what the output of an assay is about, like we have done for ‘epitope specific IFN-g production by T cells’. For the intervention type ‘assays’, we would use a ‘clinical assessment assay’ and make a subtype ‘clinical assessment of epitope specific intervention efficacy’, where the datum is_about effect of epitope specific intervention The distinction between study design execution and assay is minimally that the former is only in an investigation

16. How to guarantee interoperability study design vs. assay Chris and Jie’s use case requires tagging study designs that use certain assays (among others) Proposal: Use QTT to create defined classes for e.g. ‘microarray study design’ =def: study design and is_realized_in only (has_part some microarray assay) Define assays for all specific methodologies (e.g. FACS) and all specific types of information determined (e.g. proliferation assay) Define study designs for how comparisons between groups of patients are made (e.g. double blinded; case-control; )