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Here, we present TeaCNV, a computational framework that reconstructs clonal absolute copy number profiles and tumor clonal architectures from scATAC-seq data without matched DNA baselines. Through validation both in silico and against bulk whole-genome sequencing in renal cell carcinomas, TeaCNV resolved subclonal absolute copy number profiles with less than 10% error and detected copy number variations (CNVs) with 98.6% accuracy, outperforming existing methods. Applied to six cancer types including renal, breast, pancreatic, head and neck, colorectal, and ovarian cancers, TeaCNV delineated polyclonal architectures and revealed distinct chromatin accessibility patterns driven by CNVs in key driver genes, including AKT2, ZNF217, and SOX2. By enabling absolute copy number profiling and clonal deconvolution from epigenomic assays, TeaCNV bridges critical gaps in studying oncogenic dependencies and genotype\u2013phenotype relationships at single-cell resolution.<\/jats:p>","DOI":"10.1093\/bib\/bbag265","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:46:06Z","timestamp":1778154366000},"source":"Crossref","is-referenced-by-count":0,"title":["Inferring tumor absolute copy number and clonal substructure from single-cell chromatin accessibility"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-6147","authenticated-orcid":false,"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Guangdong Academy of Medical Sciences and Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University , No. 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]},{"name":"Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University , No. 157 Baojian Road, Nangang District, Harbin 150081 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , No. 58 Zhongshan Er Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Academy of Medical Sciences and Medical Research Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University , No. 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbao","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Urology, The Affiliated Hospital of Qingdao University , No.16 Jiangsu Road, Shinan District, Qingdao 266000, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , No. 58 Zhongshan Er Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital , No. 150 Haping Road, Nangang District, Harbin 150081 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , No. 58 Zhongshan Er Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-8165","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , No. 58 Zhongshan Er Road, Yuexiu District, Guangzhou 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhuo","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , No. 58 Zhongshan Er Road, Yuexiu District, Guangzhou 510080 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