{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:14:04Z","timestamp":1775549644888,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tuberculosis (TB) remains a significant global health challenge, necessitating reliable biomarkers for differentiation between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). This study aimed to identify blood-based biomarkers differentiating LTBI from ATB through multicohort analysis of public datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically screened 18 datasets from the NIH Gene Expression Omnibus (GEO), ultimately including 11 cohorts comprising 2,758 patients across 8 countries\/regions and 13 ethnicities. Cohorts were stratified into training (8 cohorts, <jats:italic>n<\/jats:italic>\u202f=\u202f1,933) and validation sets (3 cohorts, <jats:italic>n<\/jats:italic>\u202f=\u202f825) based on functional assignment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through Upset analysis, LASSO (Least Absolute Shrinkage and Selection Operator), SVM-RFE (Support Vector Machine Recursive Feature Elimination), and MCL (Markov Cluster Algorithm) clustering of protein\u2013protein interaction networks, we identified S100A12 and S100A8 as optimal biomarkers. A Naive Bayes (NB) model incorporating these two markers demonstrated robust diagnostic performance: training set AUC: median\u202f=\u202f0.8572 (inter-quartile range 0.8002, 0.8708), validation AUC\u202f=\u202f0.5719 (0.51645, 0.7078), and subgroup AUC\u202f=\u202f0.8635 (0.8212, 0.8946).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our multicohort analysis established an NB-based diagnostic model utilizing S100A12\/S100A8, which maintains diagnostic accuracy across diverse geographic, ethnic, and clinical variables (including HIV co-infection), highlighting its potential for clinical translation in LTBI\/ATB differentiation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1584360","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T14:28:58Z","timestamp":1746800938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Genome-wide expression in human whole blood for diagnosis of latent tuberculosis infection: a multicohort research"],"prefix":"10.3389","volume":"16","author":[{"given":"Fan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linsheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruizi","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajing","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenping","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s43556-024-00243-6","article-title":"Tuberculosis vaccines and therapeutic drug: challenges and future directions","volume":"6","author":"An","year":"2025","journal-title":"Mol. 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