Disease diagnostics using machine learning of B cell and T cell receptor sequences.

Journal: Science (New York, N.Y.)
PMID:

Abstract

Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune 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, 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 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.

Authors

  • Maxim E Zaslavsky
    Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Erin Craig
    Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Jackson K Michuda
    Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Nidhi Sehgal
    Department of Genetics, Stanford University, Stanford, CA, USA.
  • Nikhil Ram-Mohan
    Department of Emergency Medicine, Stanford University, Stanford, CA, USA.
  • Ji-Yeun Lee
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Khoa D Nguyen
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Ramona A Hoh
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Tho D Pham
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Katharina Röltgen
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
  • Brandon Lam
    Department of Pathology, Stanford University, Stanford, CA, USA.
  • Ella S Parsons
    Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
  • Susan R Macwana
    Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Wade DeJager
    Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Elizabeth M Drapeau
    Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Krishna M Roskin
    Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
  • Charlotte Cunningham-Rundles
    Division of Clinical Immunology, Icahn School of Medicine, Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, United States.
  • M Anthony Moody
    Department of Pediatrics, Duke University, Durham, NC, USA.
  • Barton F Haynes
    Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Jason D Goldman
    Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USA.
  • James R Heath
    Institute for Systems Biology, Seattle, WA, USA.
  • R Sharon Chinthrajah
    Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
  • Kari C Nadeau
    Department of Medicine, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA 94305-5101, USA.
  • Benjamin A Pinsky
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Clinical Virology Laboratory, Stanford Health Care, Palo Alto, CA 94304, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Catherine A Blish
    Department of Medicine, Stanford University, Stanford, CA, USA.
  • Scott E Hensley
    Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kent Jensen
    Department of Medicine, Stanford University, Stanford, CA, USA.
  • Everett Meyer
    Department of Medicine, Stanford University, Stanford, CA, USA.
  • Imelda Balboni
    Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Paul J Utz
    Department of Medicine, Stanford University, Stanford, CA, USA.
  • Joan T Merrill
    Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Joel M Guthridge
    Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Judith A James
    Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
  • Samuel Yang
    The Ohio State University, Columbus, OH, United States.
  • Robert Tibshirani
    Department of Statistics, Stanford University , Stanford, California 94305, United States.
  • Anshul Kundaje
    Department of Computer Science, Stanford University, Stanford, CA, USA.
  • Scott D Boyd
    Department of Pathology, Stanford University, Stanford, CA, USA.