{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:08:17Z","timestamp":1789063697350,"version":"build-2803163510"},"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether bacterial- and viral-associated whole-blood host-response modules discovered in GSE211567 retain their prespecified directions when applied unchanged to two external cohorts, including a second cross-platform cohort, and to quantify their robustness to analytical choices and gene deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five biologically guided modules were defined and fixed in GSE211567 before external analysis. The same modules were applied unchanged to GSE73461 and GSE72810 using an unweighted mean gene-wise z-score rule. Primary contrasts included 52 bacterial and 94 viral samples in GSE73461 and 23 definite bacterial and 28 definite viral samples in GSE72810. Wilcoxon tests were adjusted across the five modules using the Benjamini-Hochberg method. Hodges-Lehmann shifts, rank-biserial effects and 10,000-replicate bootstrap confidence intervals were calculated. Sensitivity analyses assessed z-score reference populations, probable-case inclusion, probe summarisation, GSVA scoring and exhaustive leave-one\/two-gene deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All five modules retained their expected directions in both projection cohorts. BACT_M2, VIR_M1a, VIR_M1b and VIR_M2 had confidence intervals excluding zero and passed false-discovery-rate correction in both cohorts, whereas BACT_M1 remained directionally concordant but borderline in GSE73461 and GSE72810 (adjusted P\u2009=\u20090.0799 in each). All 30 z-reference, case-definition and probe-collapse sensitivity estimates retained the expected direction. Under GSVA, BACT_M1 gained statistical support, whereas VIR_M2 retained its viral-higher direction but lost confidence-interval and adjusted-P-value support. Across 29,826 leave-one\/two-gene variants, every variant retained the expected direction and the minimum Pearson correlation with its complete-module score was 0.9940.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The predefined host-response modules retained their expected directions across two external cohorts measured on different Illumina platforms, with the strongest reproducible support for BACT_M2 and the three viral-associated modules. BACT_M1 and the GSVA behaviour of VIR_M2 demonstrate that direction preservation does not imply uniform statistical support across cohorts or scoring algorithms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353559","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:33:18Z","timestamp":1789061598000},"page":"e0353559","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["External transportability of bacterial- and viral-associated host-response modules across public transcriptomic cohorts"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2453-5993","authenticated-orcid":true,"given":"Reuben S.","family":"Maghembe","sequence":"first","affiliation":[{"name":"St. Francis University College of Health and Allied Sciences (SFUCHAS)","place":["Ifakara, Tanzania"],"department":["Department of Microbiology and Parasitology, Faculty of Medicine"]},{"name":"AfroBiomics Co. Ltd.","place":["Dar es Salaam, Tanzania"],"department":["Department of Omics and Computational Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"pone.0353559.ref001","doi-asserted-by":"crossref","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia","volume":"200","author":"JP Metlay","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"issue":"9","key":"pone.0353559.ref002","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.cmi.2023.05.033","article-title":"Host test based on tumor necrosis factor-related apoptosis-inducing ligand, interferon gamma-induced protein-10 and C-reactive protein for differentiating bacterial and viral respiratory tract infections in adults: diagnostic accuracy study","volume":"29","author":"S Halabi","year":"2023","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"pone.0353559.ref003","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.cmi.2021.10.019","article-title":"A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study","volume":"28","author":"C Papan","year":"2022","journal-title":"Clin Microbiol Infect"},{"issue":"9","key":"pone.0353559.ref004","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.cmi.2022.05.008","article-title":"Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children - The TREND study","volume":"28","author":"S Rhedin","year":"2022","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"pone.0353559.ref005","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults","volume":"373","author":"S Jain","year":"2015","journal-title":"N Engl J Med"},{"issue":"50","key":"pone.0353559.ref006","article-title":"Evaluation of diagnostic tests when there is no gold standard. 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