Plasma proteomics for biomarker discovery in childhood tuberculosis
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
- Jeffrey Michael Collins (ORCID: https://orcid.org/0000-0002-6574-0873)
- Andrea Fossati (ORCID: https://orcid.org/0000-0001-5170-4903)
- Mark R. Segal (ORCID: https://orcid.org/0000-0003-4213-3138)
- Esin Nkereuwem
- Zaynab Mousavian (ORCID: https://orcid.org/0009-0003-3489-126X)
- Juaneta Luiz (ORCID: https://orcid.org/0009-0005-7921-8129)
- Devan Jaganath (ORCID: https://orcid.org/0000-0002-8555-5667)
- Justin McKetney (ORCID: https://orcid.org/0000-0002-2405-8288)
- Peter Wambi (ORCID: https://orcid.org/0000-0002-9195-0778)
- Beate Kampmann (ORCID: https://orcid.org/0000-0002-6546-4709)
- Robert Castro (ORCID: https://orcid.org/0000-0002-4025-0077)
- Adithya Cattamanchi (ORCID: https://orcid.org/0000-0002-6553-2601)
- George B. Sigal (ORCID: https://orcid.org/0000-0001-7149-6400)
- Róger Calderón (ORCID: https://orcid.org/0000-0001-8932-0489)
- Molly Forrest Franke (ORCID: https://orcid.org/0000-0002-4890-5728)
- Heather Joy Zar (ORCID: https://orcid.org/0000-0002-9046-759X)
- Danielle L. Swaney (ORCID: https://orcid.org/0000-0001-6119-6084)
- Eric Wobudeya (ORCID: https://orcid.org/0000-0001-9574-5539)
- J. Ernst (ORCID: https://orcid.org/0000-0001-9951-6207)
- Rutuja Nerurkar
- Alexander Mohapatra (ORCID: https://orcid.org/0000-0003-0400-6146)
Institutions
- QB3 (US)
- South African Medical Research Council (ZA)
- Gladstone Institutes (US)
- Harvard University (US)
- Emory University (US)
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Dora Nginza Hospital (ZA)
- University of California System (US)
- Karolinska Institutet (SE)
- Malaria Consortium (UG)
- Quantitative BioSciences (US)
- MRC Unit the Gambia (GM)
- Global Brain Health Institute (US)
- Harvard Global Health Institute (US)
- Meso Scale Discovery (United States) (US)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-19
- DOI
- https://doi.org/10.1038/s41467-025-61515-5
- Citations
- 9
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- UK Research and Innovation
- South African Medical Research Council
- National Institutes of Health
- Medical Research Council