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[Preprint]. 2024 Apr 3:2022.04.26.489314. Originally published 2022 Apr 28. [Version 5] doi: 10.1101/2022.04.26.489314

Disease diagnostics using machine learning of immune receptors

Maxim E Zaslavsky, Erin Craig, Jackson K Michuda, Nidhi Sehgal, Nikhil Ram-Mohan, Ji-Yeun Lee, Khoa D Nguyen, Ramona A Hoh, Tho D Pham, Katharina Röltgen, Brandon Lam, Ella S Parsons, Susan R Macwana, Wade DeJager, Elizabeth M Drapeau, Krishna M Roskin, Charlotte Cunningham-Rundles, M Anthony Moody, Barton F Haynes, Jason D Goldman, James R Heath, Kari C Nadeau, Benjamin A Pinsky, Catherine A Blish, Scott E Hensley, Kent Jensen, Everett Meyer, Imelda Balboni, Paul J Utz, Joan T Merrill, Joel M Guthridge, Judith A James, Samuel Yang, Robert Tibshirani, Anshul Kundaje, Scott D Boyd
PMCID: PMC9094102  PMID: 35547855

Abstract

Clinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system’s own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis (Mal-ID) , 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 SARS-CoV-2, Influenza, and HIV, 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 human immune responses.

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