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Here, motivated by recent successes applying machine learning to complex biology, we curated a dataset of 651,237 unique human leukocyte antigen class I (HLA-I) ligands and developed MUNIS, a deep learning model that identifies peptides presented by HLA-I alleles. MUNIS shows improved performance compared with existing models in predicting peptide presentation and CD8<jats:sup>+<\/jats:sup> T cell epitope immunodominance hierarchies. Moreover, application of MUNIS to proteins from Epstein\u2013Barr virus led to successful identification of both established and novel HLA-I epitopes which were experimentally validated by in vitro HLA-I-peptide stability and T cell immunogenicity assays. MUNIS performs comparably to an experimental stability assay in terms of immunogenicity prediction, suggesting that deep learning can reduce experimental burden and accelerate identification of CD8<jats:sup>+<\/jats:sup> T cell epitopes for rapid T cell vaccine development.<\/jats:p>","DOI":"10.1038\/s42256-024-00971-y","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T10:03:33Z","timestamp":1738058613000},"page":"232-243","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Deep learning enhances the prediction of HLA class I-presented CD8+ T cell epitopes in foreign pathogens"],"prefix":"10.1038","volume":"7","author":[{"given":"Jeremy","family":"Wohlwend","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Nathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitan","family":"Shalon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Crain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoda","family":"Tano-Menka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0403-6181","authenticated-orcid":false,"given":"Benjamin","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6875-4472","authenticated-orcid":false,"given":"Gaurav D.","family":"Gaiha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Barzilay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"971_CR1","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.1093\/infdis\/jiaa333","volume":"223","author":"C Kaseke","year":"2021","unstructured":"Kaseke, C., Tano-Menka, R., Senjobe, F. & Gaiha, G. 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