{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T07:17:59Z","timestamp":1771226279324,"version":"3.50.1"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Tuberc."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Current diagnostic tools are limited, especially in low-resource settings. The World Health Organization's (WHO) Target Product Profiles (TPPs) call for rapid, non-sputum-based diagnostics with high sensitivity and specificity. This study evaluates our previously published TB-associated host-immune biomarkers alongside small-size signatures from other studies, in our previously published non-human primate (NHP) TB infection study dataset (GSE76703) and two previously published human datasets (GSE144127, GSE42834), which include other disease group comparators, including sarcoidosis. These were also evaluated in a small-scale, exploratory qPCR pilot study to assess the feasibility of implementing these previously validated signatures in a South Indian TB patient cohort, comparing their diagnostic performance against WHO TPP criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twenty-six genes from published signatures (INDUK, Roe1\/Roe3, Sweeney3, RISK6) were analyzed in these NHP and human datasets, using network and machine learning approaches, prior to exploratory evaluation using single and multiplex qPCR assays. These were tested using peripheral blood sample RNAs from pulmonary TB (PTB) (\n                      <jats:italic>n<\/jats:italic>\n                      = 15) and extrapulmonary TB (EPTB) (\n                      <jats:italic>n<\/jats:italic>\n                      = 15) patients and high-incidence controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 15). The diagnostic performance of biomarkers, prior signatures, and novel promising combinations were assessed against WHO TPPs for triage and confirmatory tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Several biomarker signatures successfully distinguished active TB ((ATB) PTB and EPTB combined) from controls. The minimal INDUK signature (\n                      <jats:italic>GBP1<\/jats:italic>\n                      +\n                      <jats:italic>IFIT3<\/jats:italic>\n                      ) met the optimal TPP criteria for both triage and confirmatory testing for PTB (100% sensitivity and specificity, area under the receiver operating characteristic curve (AUROC:1)) and achieved the 80% sensitivity, 100% specificity threshold for EPTB (AUROC: 0.92 CI: 0.8261\u20131.00). Combined signatures incorporating genes from INDUK, Roe1, and Sweeney3 further improved diagnostic accuracy for ATB overall (AUROC: 0.98 95% CI: 0.9472\u20131.00).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This preliminary pilot study demonstrates successful evaluation of biomarker signatures as diagnostic qPCR assays for TB diagnosis and, to our knowledge, is the first study to demonstrate the potential for combined host-immune biomarker signatures from different studies that meet WHO TPP benchmarks. These findings support the potential for the development of low-cost, field-adaptable diagnostic tools. Further validation is now under way on a larger cohort of TB patients and controls.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftubr.2025.1678039","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:36:28Z","timestamp":1771223788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of host-immune biomarker signatures as multiplex qPCR diagnostic assays: a pilot study toward meeting WHO target product profiles for TB diagnosis in India"],"prefix":"10.3389","volume":"3","author":[{"given":"Harriet N.","family":"Garlant","sequence":"first","affiliation":[{"name":"UK Health Security Agency","place":["Porton Down, Salisbury, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalaiarasan","family":"Ellappan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Jawaharlal Institute of Postgraduate Medical 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