BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data
| Autor: | Lies, Boelen, Patrick K, O'Neill, Kathryn J, Quigley, Catherine J, Reynolds, Bernard, Maillere, John H, Robinson, Ganjana, Lertmemongkolchai, Daniel M, Altmann, Rosemary J, Boyton, Becca, Asquith |
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| Rok vydání: | 2015 |
| Předmět: |
RNA viruses
Enzyme-Linked Immunospot Assay Burkholderia pseudomallei Databases Factual Physiology Epitopes T-Lymphocyte Pathology and Laboratory Medicine Biochemistry White Blood Cells Immunodeficiency Viruses Animal Cells Immune Physiology Medicine and Health Sciences Enzyme-Linked Immunoassays Immune Response Immune System Proteins T Cells Animal Models Bacterial Pathogens Medical Microbiology Viral Pathogens Viruses Cellular Types Pathogens Algorithms Research Article Burkholderia Immune Cells Immunology chemical and pharmacologic phenomena Mouse Models Research and Analysis Methods complex mixtures Microbiology Model Organisms Retroviruses Humans Computer Simulation Antigens Immunoassays Microbial Pathogens Blood Cells Bacteria Lentivirus Histocompatibility Antigens Class II Models Immunological Organisms Computational Biology Biology and Life Sciences Proteins HIV Cell Biology Melioidosis Immunologic Techniques HIV-1 Peptides Software |
| Zdroj: | PLoS Computational Biology |
| ISSN: | 1553-7358 |
| Popis: | Activation of CD4+ T cells requires the recognition of peptides that are presented by HLA class II molecules and can be assessed experimentally using the ELISpot assay. However, even given an individual’s HLA class II genotype, identifying which class II molecule is responsible for a positive ELISpot response to a given peptide is not trivial. The two main difficulties are the number of HLA class II molecules that can potentially be formed in a single individual (3–14) and the lack of clear peptide binding motifs for class II molecules. Here, we present a Bayesian framework to interpret ELISpot data (BIITE: Bayesian Immunogenicity Inference Tool for ELISpot); specifically BIITE identifies which HLA-II:peptide combination(s) are immunogenic based on cohort ELISpot data. We apply BIITE to two ELISpot datasets and explore the expected performance using simulations. We show this method can reach high accuracies, depending on the cohort size and the success rate of the ELISpot assay within the cohort. Author Summary When studying the host immune response, a central question is: “which peptides elicit CD4+ T cell responses?” ELISpot assays are used to assess if subjects have responded to a given peptide. However, to determine which of the HLA-II molecules coded by the host HLA genotype is responsible for the reaction requires additional analysis. We present a Bayesian approach to solve this problem and have implemented it for use with the statistical language R under the BIITE moniker. Importantly, the aim of BIITE is to interpret experimental data, not to make in silico predictions. The method considers the immunogenicity of all HLA (in a cohort of patients) with respect to a given peptide simultaneously, in order to deal with linkage disequilibrium between genes of the HLA locus. Furthermore, users can enter additional information they might have (from literature or other experiments) in the form of prior information. The method is not exclusive to the HLA genes and can be used to attribute positive binary outcomes to any multi-allelic set of genes. |
| Databáze: | OpenAIRE |
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