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Immune Epitope Database assays 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 Populating the IEDB Literature curation Epitope discovery contract submission IEDB www.iedb.org Structure Epitope Source Immunization Context Assay Name Chemical Type Sequence Domain / Region Species Strain Antigen Antigen Accession Antigen Positions Immunized Species Immunogen Type Administration Antigen Type Assay Type Response Measured MHC Allele 74A Peptide/Protein CLTEYILWV Defined Epitope Vaccinia virus Ankara Ankara (MVA) putative 21.7k protein 2772819 79-87 Homo sapiens Source Species Scarification Epitope ELISPOT Cytokine Release-IFN-g HLA-A*0201 Process for categorization and curation of epitope references Wang et al, BMC Bioinformatics, 2007 Literature Curation Status Journal articles Main Classes Infectious Disease Allergy Autoimmunity Transplant Total Total Relevant Outstanding % Processed 8,651 395 98.9 768 38 98.3 3,889 2,858 47.5 605 582 3.8 13,913 3,873 80.4 On track to be complete by end of this year epitope source (material entity) organism protein protein complex High level database structure has part peptide epitope structure (material entity) discontinuous protein residues is about reference (document) journal article author submission carbohydrate has participant immune recognition assay (process) B cell response T cell response MHC binding preceded by immunization (process) Natural Infection Administered Immunization Vita et al, NAR, 2009 High level assay types T APC MHC Binding MHC Ligand Elution T B APC T Cell Response B Cell Response T cell assay example: IFN-g ELISA T APC ell Response • ELISA =def: an assay where an enzyme linked antibody is used to detect a plate bound material in a liquid (the evaluant) utilizing a B 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 Response • BT Cell 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. No peptide With peptide T T APC APC With IFNg antibody Without IFNg antibody QTT 1 – epitope specific GO processes GO:process GO ID rdfs:label (Label should be: "epitope specific @A by T cells") interleukin-2 production GO_0032623 epitope specific interleukin-2 production by T cells GO_0042098 epitope specific T cell proliferation Definition A process of interleukin-2 production by T cells resulting from the recognition of a T cell epitope. T cell proliferation A process of T cell proliferation resulting from the recognition of a T cell epitope. T cell mediated cytotoxicity GO_0001913 epitope specific T cell mediated A process of T cell mediated cytotoxicity cytotoxicity resulting from the recognition of a T cell epitope. tolerance induction GO_0002507 epitope specific tolerance induction by A process of tolerance induction by T cells T cells resulting from the recognition of a T cell epitope. Definition editor PERSON:Randi Vita, Jason Greenbaum, Bjoern Peters PERSON:Randi Vita, Jason Greenbaum, Bjoern PERSON:Randi Vita, Jason Greenbaum, Bjoern PERSON:Randi Vita, Jason Greenbaum, Bjoern •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 Assay techniques • Created general assays in OBI 3H-thymidine proliferation assay 51 chromium release assay assay BrdU incorporation assay cytokine bioassay cytometric bead array ELISA ELISPOT flow cytometry assay in vivo assay intracellular staining assay MHC tetramer/multimer staining radio immuno assay (RIA) reporter gene assay RNA/DNA detection assay surface plasmon resonance response assay x-ray crystallography QTT 2 – T cell epitope assays IEDB IEDB label Assay ID OBI ID of epitope OBI ID of specific biological technique process 198 cell proliferation assay (any/other) OBI_1110182 49 cytokine release-IL-2 assay (ELISPOT) OBI_1110056 48 cytokine release-IFNg assay (ELISPOT) OBI_1110185 67 cytotoxicity assay (51 chromium release) OBI_1110204 73 cytokine release-IFNg assay (ELISA) OBI_1110185 rdfs:label (could be: 'assay type label' of 'is about label' OBI_0000070 assay of epitope specific T cell proliferation by T cells OBI_0600031 ELISPOT assay of epitope specific interleukin-2 production OBI_0600031 ELISPOT assay of epitope specific interferon-gamma OBI_9999994 chromium release assay of epitope specific killing by T cells OBI_0000661 ELISA of epitope specific interferon-gamma production by T Definition Measuring epitope specific T cell proliferation by T cells using an assay Measuring epitope specific interleukin-2 production by T cells using an ELISPOT Measuring epitope specific interferongamma production by T cells using an Measuring epitope specific killing by T cells using a chromium release assay Measuring epitope specific interferongamma production by T cells using an • 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 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 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 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 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; )