{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:00:11Z","timestamp":1790312411394,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>DNA damage repair-related genes (DDR-RGs) may shape tuberculosis (TB) pathogenesis, but their molecular characteristics, diagnostic utility, and cellular context remain insufficiently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated multiple GEO transcriptome datasets, identified differentially expressed genes, constructed weighted gene co-expression network analysis modules, and intersected these results with curated DDR-RGs to obtain candidate genes. An ensemble framework of 110 machine-learning model combinations was used to select diagnostic markers, followed by external validation, consensus clustering, immune infiltration analysis, single-cell RNA-seq evaluation, and Comparative Toxicogenomics Database-based compound-association analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The integrated training cohort included 134 samples; 94 differentially expressed genes and a 392-gene key module were identified, yielding 25 candidate DDR-RGs. The Ridge + SVM model performed best and selected ETV7, STAT1, FBXO6, and TAP1 as core DDR-RGs, achieving AUCs of 0.991, 0.925, 0.939, and 0.981 in the training and three validation cohorts. Consensus clustering separated TB patients into two DDR-related subtypes, with Cluster 1 enriched in immune-related pathways and characterized by distinct immune-cell infiltration. Single-cell analysis revealed cell-type-specific expression of core DDR-RGs in pulmonary TB, and compound-association analysis identified 35 candidate compounds, including six associated with multiple core genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings characterize DDR-related molecular heterogeneity in TB and support ETV7, STAT1, FBXO6, and TAP1 as candidate diagnostic biomarkers and exploratory candidates for host-directed studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1885489","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:28:05Z","timestamp":1790310485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA damage repair-related gene signatures delineate immune-distinct subtypes and diagnostic cues in tuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Abdusemer","family":"Reyimu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamatali","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Abudurousuli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Kashi","place":["Xinjiang, Kashi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","volume-title":"Cell Ranger Support Documentation","year":"2026"},{"key":"B2","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. 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