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Plasma proteomics for biomarker discovery in childhood tuberculosis

Author

Listed:
  • Andrea Fossati

    (J. David Gladstone Institutes
    University of California San Francisco
    University of California San Francisco)

  • Peter Wambi

    (Kololo)

  • Devan Jaganath

    (University of California San Francisco
    University of California San Francisco)

  • Roger Calderon

    (Advanced Research and Health)

  • Robert Castro

    (University of California San Francisco
    University of California San Francisco)

  • Alexander Mohapatra

    (University of California San Francisco
    San Francisco)

  • Justin McKetney

    (J. David Gladstone Institutes
    University of California San Francisco
    University of California San Francisco)

  • Juaneta Luiz

    (University of Cape Town
    Dora Nginza Hospital)

  • Rutuja Nerurkar

    (University of California San Francisco
    University of California San Francisco)

  • Esin Nkereuwem

    (MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine)

  • Molly F. Franke

    (Harvard Medical School)

  • Zaynab Mousavian

    (Karolinska Institutet
    Emory University)

  • Jeffrey M. Collins

    (Emory University School of Medicine)

  • George B. Sigal

    (Meso Scale Diagnostics, LLC.)

  • Mark R. Segal

    (University of California San Francisco)

  • Beate Kampman

    (MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine
    Charité Universitätsmedizin Berlin)

  • Eric Wobudeya

    (Kololo)

  • Adithya Cattamanchi

    (University of California San Francisco
    University of California Irvine)

  • Joel D. Ernst

    (University of California San Francisco
    San Francisco)

  • Heather J. Zar

    (University of Cape Town)

  • Danielle L. Swaney

    (J. David Gladstone Institutes
    University of California San Francisco
    University of California San Francisco)

Abstract

Failure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, thus a global priority is the identification of novel non-sputum-based TB biomarkers. Here we use high-throughput proteomics to measure the plasma proteome for 511 children, with and without HIV, and across 4 countries, to distinguish TB status using standardized definitions. By employing a machine learning approach, we derive four parsimonious biosignatures encompassing 3 to 6 proteins that achieve AUCs of 0.87–0.88 and which all reach the minimum WHO target product profile accuracy thresholds for a TB screening test. This work provides insights into the unique host response in pediatric TB disease, as well as a non-sputum biosignature that could reduce delays in TB diagnosis and improve the detection and management of TB in children worldwide.

Suggested Citation

  • Andrea Fossati & Peter Wambi & Devan Jaganath & Roger Calderon & Robert Castro & Alexander Mohapatra & Justin McKetney & Juaneta Luiz & Rutuja Nerurkar & Esin Nkereuwem & Molly F. Franke & Zaynab Mous, 2025. "Plasma proteomics for biomarker discovery in childhood tuberculosis," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61515-5
    DOI: 10.1038/s41467-025-61515-5
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