{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:32:31Z","timestamp":1782513151814,"version":"3.54.5"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002733"],"award-info":[{"award-number":["UL1TR002733"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug combinations have exhibited promising therapeutic effects in treating cancer patients with less toxicity and adverse side effects. However, it is infeasible to experimentally screen the enormous search space of all possible drug combinations. Therefore, developing computational models to efficiently and accurately identify potential anti-cancer synergistic drug combinations has attracted a lot of attention from the scientific community. Hypothesis-driven explicit mathematical methods or network pharmacology models have been popular in the last decade and have been comprehensively reviewed in previous surveys. With the surge of artificial intelligence and greater availability of large-scale datasets, machine learning especially deep learning methods are gaining popularity in the field of computational models for anti-cancer drug synergy prediction. Machine learning-based methods can be derived without strong assumptions about underlying mechanisms and have achieved state-of-the-art prediction performances, promoting much greater growth of the field. Here, we present a structured overview of available large-scale databases and machine learning especially deep learning methods in computational predictive models for anti-cancer drug synergy prediction. We provide a unified framework for machine learning models and detail existing model architectures as well as their contributions and limitations, shedding light into the future design of computational models. Besides, unbiased experiments are conducted to provide in-depth comparisons between reviewed papers in terms of their prediction performance.<\/jats:p>","DOI":"10.1093\/bib\/bbab271","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T19:12:51Z","timestamp":1627931571000},"source":"Crossref","is-referenced-by-count":69,"title":["Artificial intelligence and machine learning methods in predicting anti-cancer drug combination effects"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-1177","authenticated-orcid":false,"given":"Kunjie","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics of The Ohio State University, 43202 Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics of The Ohio State University, 43202 Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics of The Ohio State University, 43202 Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"2021110815073238200_ref1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms of drug combinations: interaction and network perspectives","volume":"8","author":"Jia","year":"2009","journal-title":"Nat Rev Drug Discov"},{"key":"2021110815073238200_ref2","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1158\/1535-7163.MCT-15-0843","article-title":"An unbiased oncology compound screen to identify novel combination strategies","volume":"15","author":"O'Neil","year":"2016","journal-title":"Mol Cancer 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