{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:11:59Z","timestamp":1790327519816,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1105200"],"award-info":[{"award-number":["2022YFA1105200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFA1800700"],"award-info":[{"award-number":["2023YFA1800700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773012"],"award-info":[{"award-number":["81773012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lung cancer is characterised by high mortality and encompasses various subtypes with markedly different treatment outcomes. While individual subtypes have been studied, comprehensive genome\u2010wide and fine\u2010scale DNA methylation analyses across subtypes remain unexplored. This study aims to identify true subtype\u2010specific aberrant methylation by developing a novel method that eliminates cell\u2010origin and immune confounding, moving beyond traditional approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We assembled an in\u2010house cohort of 115 tissue samples across five groups (CTL, LUAD, LUSC, LCC, SCLC) with detailed clinicopathological annotations. Matched plasma cfDNA samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a024; 9 LUAD, 7 LUSC, 8 healthy) were collected for translational assessment. We developed an MV analysis method implemented in the open\u2010source toolkit pattools to differentiate cell\u2010specific fragments in bulk BS\u2010seq data and identify subtype\u2010specific methylation vector regions (SMVRs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genome\u2010wide methylation profiling revealed that subtype\u2010specific signals originate from distinct cell types\u2014alveolar epithelium in LUAD, head and neck epithelium in LUSC, fibroblasts in LCC, and endocrine cells in SCLC\u2014with additional immune infiltration influences. Using pattools\u2010based MV analysis, we identified 500 key SMVRs per subtype. In matched plasma cfDNA, these tissue\u2010derived SMVRs demonstrated promising discriminatory power for LUAD (AUC\u00a0=\u00a00.98, 95% CI: 0.95 to 1.00) and LUSC (AUC\u00a0=\u00a00.88, 95% CI: 0.79 to 0.97) in binary classification, and AUCs of 0.95 (95% CI: 0.90 to 1.00), 0.75 (95% CI: 0.62 to 0.88), and 0.63 (95% CI: 0.48 to 0.78) for LUAD, LUSC and healthy samples, respectively, in multi\u2010class classification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The MV analysis in pattools effectively uncovers subtype\u2010specific aberrant methylation signals, offering potential for precise diagnosis and subtyping in tissue and liquid biopsy. Independent validation in larger cohorts is required before clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70812","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:29:56Z","timestamp":1787909396000},"source":"Crossref","is-referenced-by-count":0,"title":["Pattools\u2011implemented methylation vector analysis reveals aberrant subtype\u2011specific methylation in lung cancer across tissue and plasma cfDNA"],"prefix":"10.1002","volume":"16","author":[{"given":"Zehua","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Cardiology of the Second Affiliated Hospital, School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Zhejiang University  Hangzhou China"},{"name":"Heart Regeneration and Repair Key Laboratory of Zhejiang Province  Hangzhou 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Devices Zhejiang University  Hangzhou China"},{"name":"Heart Regeneration and Repair Key Laboratory of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoling","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transvascular Implantation Devices Zhejiang University  Hangzhou China"},{"name":"Department of Research and Development Zhejiang Gaomei Genomics  Hangzhou China"},{"name":"Information and Communication Engineering Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology of the Second Affiliated Hospital, School of Medicine Zhejiang University  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices Zhejiang University  Hangzhou China"},{"name":"Heart Regeneration and Repair Key Laboratory of Zhejiang Province  Hangzhou 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