Plasma proteomics for biomarker discovery in childhood tuberculosis.

Journal: Nature communications
Published Date: Jul 19, 2025

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.

Authors

  • Andrea Fossati
    Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Peter Wambi
    Uganda Tuberculosis Implementation Research Consortium, Walimu, Kololo, Kampala, Uganda.
  • Devan Jaganath
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Roger Calderon
    Advanced Research and Health, Lima, Peru.
  • Robert Castro
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Alexander Mohapatra
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Justin McKetney
    Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Juaneta Luiz
    Department of Pediatrics and Child Health, South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
  • Rutuja Nerurkar
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Esin Nkereuwem
    Vaccines and Immunity Theme, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
  • Molly F Franke
    Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
  • Zaynab Mousavian
    Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Jeffrey M Collins
    Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • George B Sigal
    Meso Scale Diagnostics, LLC., Rockville, MD, USA.
  • Mark R Segal
    Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • Beate Kampman
    Vaccines and Immunity Theme, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
  • Eric Wobudeya
    Uganda Tuberculosis Implementation Research Consortium, Walimu, Kololo, Kampala, Uganda.
  • Adithya Cattamanchi
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Joel D Ernst
    Institute for Global Health Sciences, Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.
  • Heather J Zar
    Department of Pediatrics and Child Health, South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa. heather.zar@uct.ac.za.
  • Danielle L Swaney
    J. David Gladstone Institutes, San Francisco, CA, USA. danielle.swaney@ucsf.edu.

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