{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:51:46Z","timestamp":1776444706551,"version":"3.51.2"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572072"],"award-info":[{"award-number":["81572072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["17JC1404500"],"award-info":[{"award-number":["17JC1404500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["16441907200"],"award-info":[{"award-number":["16441907200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatitis B virus (HBV) infection is one of the main leading causes of hepatocellular carcinoma (HCC) worldwide. However, it remains uncertain how the reverse-transcriptase (rt) gene contributes to HCC progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled a total of 307 patients with chronic hepatitis B (CHB) and 237 with HBV-related HCC from 13 medical centers. Sequence features comprised multidimensional attributes of rt nucleic acid and rt\/s amino acid sequences. Machine-learning models were used to establish HCC predictive algorithms. Model performances were tested in the training and independent validation cohorts using receiver operating characteristic curves and calibration plots.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A random forest (RF) model based on combined metrics (10 features) demonstrated the best predictive performances in both cross and independent validation (AUC, 0.96; accuracy, 0.90), irrespective of HBV genotypes and sequencing depth. Moreover, HCC risk scores for individuals obtained from the RF model (AUC, 0.966; 95% confidence interval, .922\u2013.989) outperformed \u03b1-fetoprotein (0.713; .632\u2013.784) in distinguishing between patients with HCC and those with CHB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study provides evidence for the first time that HBV rt sequences contain vital HBV quasispecies features in predicting HCC. Integrating deep sequencing with feature extraction and machine-learning models benefits the longitudinal surveillance of CHB and HCC risk assessment.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiaa647","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T03:45:07Z","timestamp":1602128707000},"page":"1887-1896","source":"Crossref","is-referenced-by-count":22,"title":["Using Quasispecies Patterns of Hepatitis B Virus to Predict Hepatocellular Carcinoma With Deep Sequencing and Machine Learning"],"prefix":"10.1093","volume":"223","author":[{"given":"Shipeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"ISTBI and Shanghai Key Lab of Intelligent Information Processing, Fudan University, Shanghai, 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