{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:02:29Z","timestamp":1790647349905,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,5,18]],"date-time":"2019-05-18T00:00:00Z","timestamp":1558137600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Science and Technology Major Project of the Ministry of Science and Technology of China","award":["2018ZX10301402"],"award-info":[{"award-number":["2018ZX10301402"]}]},{"name":"Nature and Science Foundation of China","award":["81761148025"],"award-info":[{"award-number":["81761148025"]}]},{"name":"Guangzhou Science and Technology Programme","award":["201704020093"],"award-info":[{"award-number":["201704020093"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["17ykzd15"],"award-info":[{"award-number":["17ykzd15"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Three Big Constructions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, \u2018common\u2019 deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.<\/jats:p>","DOI":"10.1093\/carcin\/bgz094","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T07:10:59Z","timestamp":1557990659000},"page":"1220-1228","source":"Crossref","is-referenced-by-count":39,"title":["Risk stratification of cervical lesions using capture sequencing and machine learning method based on HPV and human integrated genomic profiles"],"prefix":"10.1093","volume":"40","author":[{"given":"Rui","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Precision Medicine Institute, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifeng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Precision Medicine Institute, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Academician Expert Workstation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Urology, The General Hospital of the People\u2019s Liberation Army, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-rong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhudev C","family":"Das","sequence":"additional","affiliation":[{"name":"Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, 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University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Precision Medicine Institute, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiling","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Precision Medicine Institute, Sun Yat-sen University, Yuexiu, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyue","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and 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