{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:24:28Z","timestamp":1793053468975,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Innovation Fund for Medical Sciences","award":["2022-I2M-C&T-B-118"],"award-info":[{"award-number":["2022-I2M-C&T-B-118"]}]},{"DOI":"10.13039\/501100016359","name":"Zhongnan Hospital of Wuhan University","doi-asserted-by":"publisher","award":["ZNJC202210"],"award-info":[{"award-number":["ZNJC202210"]}],"id":[{"id":"10.13039\/501100016359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016359","name":"Zhongnan Hospital of Wuhan University","doi-asserted-by":"publisher","award":["PTXM2021001"],"award-info":[{"award-number":["PTXM2021001"]}],"id":[{"id":"10.13039\/501100016359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12375349"],"award-info":[{"award-number":["12375349"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002672"],"award-info":[{"award-number":["82002672"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373436"],"award-info":[{"award-number":["82373436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Hospitals Authority\u2019 Youth Program","award":["QML20230114"],"award-info":[{"award-number":["QML20230114"]}]},{"name":"Natural Science Foundation of Hubei Province of China","award":["2023AFB521"],"award-info":[{"award-number":["2023AFB521"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2662021JC008"],"award-info":[{"award-number":["2662021JC008"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2662023XXPY003"],"award-info":[{"award-number":["2662023XXPY003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool\u2019s diagnostic capability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae156","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T23:16:36Z","timestamp":1727910996000},"page":"1463-1473","source":"Crossref","is-referenced-by-count":19,"title":["Machine Learning-Based Detection of Bladder Cancer by Urine cfDNA Fragmentation Hotspots that Capture Cancer-Associated Molecular Features"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5669-3502","authenticated-orcid":false,"given":"Xiang-Yu","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Urology, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]},{"name":"Hubei Provincial Clinical Medical Research Center for Nephropathy, Hubei Minzu University , Enshi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-1091","authenticated-orcid":false,"given":"Xiong-Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]},{"name":"Center for Single-cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Friendship Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan-Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Friendship Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Friendship Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]},{"name":"Center for Single-cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Zhen","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]},{"name":"Center for Single-cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-4401","authenticated-orcid":false,"given":"Hong-Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University , Wuhan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Friendship Hospital, Capital Medical University , Beijing 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