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<p>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.</p>

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Plasma proteomics for biomarker discovery in childhood tuberculosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月19日

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  • Andrea Fossati,
  • Peter Wambi,
  • Devan Jaganath,
  • Roger Calderon,
  • Robert Castro,
  • Alexander Mohapatra,
  • Justin McKetney,
  • Juaneta Luiz,
  • Rutuja Nerurkar,
  • Esin Nkereuwem,
  • Molly F. Franke,
  • Zaynab Mousavian,
  • Jeffrey M. Collins,
  • George B. Sigal,
  • Mark R. Segal,
  • Beate Kampman,
  • Eric Wobudeya,
  • Adithya Cattamanchi,
  • Joel D. Ernst,
  • Heather J. Zar,
  • Danielle L. Swaney

摘要

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.