{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T08:02:48Z","timestamp":1773734568612,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012600","name":"ShanghaiTech University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012600","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Commission\u2019s key laboratory of individualized diagnosis and treatment of nasopharyngeal cancer","award":["2023NPCCK02"],"award-info":[{"award-number":["2023NPCCK02"]}]},{"name":"cross-disciplinary Research Fund of Shanghai Ninth People\u2019s Hospital, Shanghai JiaoTong University School of Medicine","award":["JYJC202227"],"award-info":[{"award-number":["JYJC202227"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373149"],"award-info":[{"award-number":["82373149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["24J22800700"],"award-info":[{"award-number":["24J22800700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Low-coverage whole-genome sequencing (lcWGS) provides a cost-effective method for genome-wide copy number variation (CNV) profiling, yet its technical limitations and analytical variability require systematic evaluation. We benchmarked five CNV detection tools using simulated and real-world datasets, focusing on sequencing depth, formalin-fixed paraffin-embedded (FFPE) artifacts, tumor purity, multi-center reproducibility, and signature-level stability. Our results demonstrate that ichorCNA outperformed other tools in precision and runtime at high purity (\u226550%), making it the optimal choice for lcWGS-based workflows. Prolonged FFPE fixation induced artifactual short-segment CNVs due to formalin-driven DNA fragmentation, a bias none of the tools could computationally correct, necessitating strict fixation time control or prioritization of fresh-frozen samples. Multi-center analysis revealed high reproducibility for the same tool across sequencing facilities, but comparisons between different tools showed low concordance. Copy number features extracted by the Wang et\u00a0al. method exhibited superior stability across conditions compared with the Steele et\u00a0al. method and the Tao et\u00a0al. method. This study establishes actionable guidelines for lcWGS: prioritize ichorCNA (ensuring \u226550% tumor purity), optimize FFPE protocol, and use Wang et\u00a0al. features to ensure robust copy number profiling in precision oncology.<\/jats:p>","DOI":"10.1093\/bib\/bbaf514","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:32:12Z","timestamp":1759235532000},"source":"Crossref","is-referenced-by-count":2,"title":["Benchmarking copy number variation detection with low-coverage whole-genome sequencing"],"prefix":"10.1093","volume":"26","author":[{"given":"Nan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University , 393 Middle Huaxia Road, Pudong New Area, Shanghai, 201210 ,","place":["China"]}]},{"given":"Zi-Yu","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 227 South Chongqing Road, Shanghai, 200025 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-9628","authenticated-orcid":false,"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University , 393 Middle Huaxia Road, Pudong New Area, Shanghai, 201210 ,","place":["China"]},{"name":"Department of Dermatology, Yangjiang People's Hospital Affiliated to Guangdong Medical University , 42 Dongshan Road, Jiangcheng District, Yangjiang, Guangdong, 529525 ,","place":["China"]}]},{"given":"Jinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University , 393 Middle Huaxia Road, Pudong New Area, Shanghai, 201210 ,","place":["China"]}]},{"given":"Weiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yangjiang People's Hospital Affiliated to Guangdong Medical University , 42 Dongshan Road, Jiangcheng District, Yangjiang, Guangdong, 529525 ,","place":["China"]}]},{"given":"Huaqiu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Gannan Medical University , 23 Qingnian Road, Zhanggong, Ganzhou, Jiangxi, 341000 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-0077","authenticated-orcid":false,"given":"Xue-Song","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University , 393 Middle Huaxia Road, Pudong New Area, Shanghai, 201210 ,","place":["China"]},{"name":"Shanghai Clinical Research and Trial Center , 1599 Keyuan Road, Pudong New Area, Shanghai (Temporary), Shanghai, 201210 ,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"2025093008315116800_ref1","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/nature05329","article-title":"Global variation in copy 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