A machine learning and centrifugal microfluidics platform for bedside prediction of sepsis.

Journal: Nature communications
Published Date: May 27, 2025

Abstract

Sepsis is a life-threatening organ dysfunction due to a dysfunctional response to infection. Delays in diagnosis have substantial impact on survival. Herein, blood samples from 586 in-house patients with suspected sepsis are used in conjunction with machine learning and cross-validation to define a six-gene expression signature of immune cell reprogramming, termed Sepset, to predict clinical deterioration within the first 24 h (h) of clinical presentation. Prediction accuracy (~90% in early intensive care unit (ICU) and 70% in emergency room patients) is validated in 3178 patients from existing independent cohorts. A RT-PCR-based Sepset detection test shows a 94% sensitivity in 248 patients to predict worsening of the sequential organ failure assessment scores within the first 24 h. A stand-alone centrifugal microfluidic instrument that automates whole-blood Sepset classifier detection is tested, showing a sensitivity of 92%, and specificity of 89% in identifying the risk of clinical deterioration in patients with suspected sepsis.

Authors

  • Lidija Malic
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Peter G Y Zhang
    Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada.
  • Pamela J Plant
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • Liviu Clime
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Christina Nassif
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Dillon Da Fonte
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Evan E Haney
    Sepset Biosciences Inc., 420 - 730 View St, Victoria, BC, V8W 3S2, Canada.
  • Byeong-Ui Moon
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Victor Min-Sung Sit
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Daniel Brassard
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Maxence Mounier
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Eryn Churcher
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • James T Tsoporis
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • Reza Falsafi
    Centre for Microbial Diseases and Immunity Research, University of British Colombia, 232-2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada.
  • Manjeet Bains
    Centre for Microbial Diseases and Immunity Research, University of British Colombia, 232-2259 Lower Mall, Vancouver, BC, V6T 1Z4, Canada.
  • Andrew Baker
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • Uriel Trahtemberg
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • Ljuboje Lukic
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • John C Marshall
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Critical Care Medicine, 30 Bond Street, Toronto, ON, M5G 1W8, Canada.
  • Matthias Geissler
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Robert E W Hancock
    Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
  • Teodor Veres
    Life Sciences Division, National Research Council of Canada, 75 de Mortagne Boulevard, Boucherville, QC, J4B 6Y4, Canada.
  • Claudia C Dos Santos
    Keenan Research Center for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada. dossantosC@unityhealth.to.

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