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.
Competing Interest Statement
M.E.Z., E.C., J.K.M., N.S., R.T., A.K., and S.D.B. are co-inventors on patent applications related to this manuscript. S.D.B. has consulted for Regeneron, Sanofi, Novartis, and Janssen on topics unrelated to this study and owns stock in AbCellera Biologics. A.K. is scientific co-founder of Ravel Biotechnology Inc., is on the scientific advisory board of PatchBio Inc., SerImmune Inc., AINovo Inc., TensorBio Inc. and OpenTargets, was a consultant with Illumina Inc. and owns shares in DeepGenomics Inc., Immunai Inc., and Freenome Inc. C.A.B. reports compensation for consulting and/or SAB membership from Catamaran Bio, DeepCell Inc., Immunebridge, Sangamo Therapeutics, and Revelation Biosciences on topics unrelated to this study. J.D.G. has consulted for Eli Lilly, Gilead, GSK, and Karius, and reports research support from Eli Lilly, Gilead, Regeneron, Merck, and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and Labcorp (outside of this study). R.T is a consultant for Genentech. J.A.J. has served as a consultant for AbbVie, Janssen, Novartis, and GlaxoSmithKline. J.A.J. also has unrelated patents through the Oklahoma Medical Research Foundation which the foundation has licensed to Progentec Biosciences, LLC. J.T.M has served as a consultant for AbbVie, Alexion, Alumis, Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Lilly, Merck, Pfizer, Provention, Remegen, Sanofi, UCB, and Zenas, and reports research support from AstraZeneca, Bristol Myers Squibb, and GlaxoSmithKline (outside of this study). K.C.N. is an inventor or co-inventor on unrelated patents, is a scientific co-founder of Alladapt, BeforeBrands, IgGenix, and Latitude, owns stock in those and Seed, Excellergy, ClostraBio, and Cour Pharmaceuticals. K.C.N. has consulted for Regeneron and Novartis on topics unrelated to this study. S.E.H. reports receiving consulting fees from Sanofi Vaccines, Lumen, Novavax, and Merck. S.E.H. is a co-inventor on patents that describe the use of nucleoside-modified mRNA as a vaccine platform. J.R.H. is a consultant for Regeneron and has received research support from Merck and Gilead. Other co-authors declare that they have no competing interests.
Footnotes
Additional disease classes, improved methodology, additional validation