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We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis, an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences. Human-interpretable features of the model recapitulate known immune responses to severe acute respiratory syndrome\n                    <jats:italic>coronavirus<\/jats:italic>\n                    2, influenza, and human immunodeficiency virus, highlight antigen-specific receptors, and reveal distinct characteristics of systemic lupus erythematosus and type-1 diabetes autoreactivity. This analysis framework has broad potential for scientific and clinical interpretation of immune responses.\n                  <\/jats:p>","DOI":"10.1126\/science.adp2407","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T14:00:06Z","timestamp":1740060006000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":102,"title":["Disease diagnostics using machine learning of B cell and T cell receptor sequences"],"prefix":"10.1126","volume":"387","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-7854","authenticated-orcid":true,"given":"Maxim E.","family":"Zaslavsky","sequence":"first","affiliation":[{"name":"Department of Computer Science, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4893-6671","authenticated-orcid":true,"given":"Erin","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-7693","authenticated-orcid":true,"given":"Jackson K.","family":"Michuda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University, Stanford, CA, USA."},{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-2772","authenticated-orcid":true,"given":"Nikhil","family":"Ram-Mohan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0463-6802","authenticated-orcid":true,"given":"Ji-Yeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-3621","authenticated-orcid":true,"given":"Khoa D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-1942","authenticated-orcid":true,"given":"Ramona A.","family":"Hoh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tho D.","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."},{"name":"Stanford Blood Center, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-1720","authenticated-orcid":true,"given":"Katharina","family":"R\u00f6ltgen","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland."},{"name":"University of Basel, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-2000","authenticated-orcid":true,"given":"Brandon","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-4173","authenticated-orcid":true,"given":"Ella S.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Sean N. 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