{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:48:58Z","timestamp":1775263738284,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFF1203005"],"award-info":[{"award-number":["2022YFF1203005"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81925034"],"award-info":[{"award-number":["81925034"]}],"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":["22237005"],"award-info":[{"award-number":["22237005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["2019-01-07-00-01-E00036"],"award-info":[{"award-number":["2019-01-07-00-01-E00036"]}]},{"name":"Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study","award":["SN-ZJU-SIAS-007"],"award-info":[{"award-number":["SN-ZJU-SIAS-007"]}]},{"DOI":"10.13039\/100020732","name":"Innovative research team of high-level local universities in Shanghai","doi-asserted-by":"crossref","award":["SHSMU-ZDCX20212700"],"award-info":[{"award-number":["SHSMU-ZDCX20212700"]}],"id":[{"id":"10.13039\/100020732","id-type":"DOI","asserted-by":"crossref"}]},{"name":"GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine"},{"DOI":"10.13039\/100016692","name":"Key Research and Development Program of Ningxia Hui Autonomous Region","doi-asserted-by":"publisher","award":["2022CMG01002"],"award-info":[{"award-number":["2022CMG01002"]}],"id":[{"id":"10.13039\/100016692","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Health and Family Planning Commission","award":["201940287"],"award-info":[{"award-number":["201940287"]}]},{"name":"Shanghai Science and Technology Innovation Fund","award":["22Y21900800"],"award-info":[{"award-number":["22Y21900800"]}]},{"name":"Shanghai Science and Technology Innovation Fund","award":["22Y11906000"],"award-info":[{"award-number":["22Y11906000"]}]},{"name":"Shanghai Sailing Program","award":["21YF1422500"],"award-info":[{"award-number":["21YF1422500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Driver mutations can contribute to the initial processes of cancer, and their identification is crucial for understanding tumorigenesis as well as for molecular drug discovery and development. Allostery regulates protein function away from the functional regions at an allosteric site. In addition to the known effects of mutations around functional sites, mutations at allosteric sites have been associated with protein structure, dynamics, and energy communication. As a result, identifying driver mutations at allosteric sites will be beneficial for deciphering the mechanisms of cancer and developing allosteric drugs. In this study, we provided a platform called DeepAlloDriver to predict driver mutations using a deep learning method that exhibited\u00a0&amp;gt;93% accuracy and precision. Using this server, we found that a missense mutation in RRAS2 (Gln72 to Leu) might serve as an allosteric driver of tumorigenesis, revealing the mechanism of the mutation in knock-in mice and cancer patients. Overall, DeepAlloDriver would facilitate the elucidation of the mechanisms underlying cancer progression and help prioritize cancer therapeutic targets. The web server is freely available at: https:\/\/mdl.shsmu.edu.cn\/DeepAlloDriver.<\/jats:p>","DOI":"10.1093\/nar\/gkad295","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T12:25:35Z","timestamp":1681993535000},"page":"W129-W133","source":"Crossref","is-referenced-by-count":22,"title":["DeepAlloDriver: a deep learning-based strategy to predict cancer driver mutations"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4682-5556","authenticated-orcid":false,"given":"Qianqian","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"},{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Mingyu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Xun","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"},{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Kun","family":"Song","sequence":"additional","affiliation":[{"name":"Nutshell Therapeutics , Shanghai \u00a0201210, China"}]},{"given":"Ziliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Jiale","family":"Wei","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"},{"name":"Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200011, China"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong , Hong Kong\u00a0 999077 , China"}]},{"given":"Jiacheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"},{"name":"Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200011, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-4710","authenticated-orcid":false,"given":"Youqiong","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"}]},{"given":"Jinyin","family":"Zha","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Qiufen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Qiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University , Shanghai , China"}]},{"given":"Jiang","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200080, China"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"}]},{"given":"Xuefeng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200011, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-791X","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China"},{"name":"Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine , Shanghai \u00a0200025, China"},{"name":"School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou \u00a0450001, China"}]}],"member":"286","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"2023070504591867500_B1","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/nrc2013","article-title":"Cancer as an evolutionary and ecological process","volume":"6","author":"Merlo","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"2023070504591867500_B2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-pathol-012414-040312","article-title":"Driver and passenger mutations in cancer","volume":"10","author":"Pon","year":"2015","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"2023070504591867500_B3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/446145a","article-title":"Drivers and passengers","volume":"446","author":"Haber","year":"2007","journal-title":"Nature"},{"key":"2023070504591867500_B4","doi-asserted-by":"crossref","first-page":"18545","DOI":"10.1073\/pnas.1010978107","article-title":"Accumulation of driver and passenger mutations during tumor progression","volume":"107","author":"Bozic","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2023070504591867500_B5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12859-020-3449-2","article-title":"QuaDMutNetEx: a method for detecting cancer driver genes with low mutation frequency","volume":"21","author":"Bokhari","year":"2020","journal-title":"BMC Bioinf."},{"key":"2023070504591867500_B6","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1186\/gb-2012-13-12-r124","article-title":"DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer","volume":"13","author":"Bashashati","year":"2012","journal-title":"Genome Biol."},{"key":"2023070504591867500_B7","doi-asserted-by":"crossref","first-page":"1800640","DOI":"10.1002\/advs.201800640","article-title":"MaxMIF: a new method for identifying cancer driver genes through effective data integration","volume":"5","author":"Hou","year":"2018","journal-title":"Adv. Sci."},{"key":"2023070504591867500_B8","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/gkz096","article-title":"DriverML: a machine learning algorithm for identifying driver genes in cancer sequencing studies","volume":"47","author":"Han","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/bioinformatics\/bty511","article-title":"ncdDetect2: improved models of the site-specific mutation rate in cancer and driver detection with robust significance evaluation","volume":"35","author":"Juul","year":"2018","journal-title":"Bioinformatics"},{"key":"2023070504591867500_B10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12859-016-0935-7","article-title":"LowMACA: exploiting protein family analysis for the identification of rare driver mutations in cancer","volume":"17","author":"Melloni","year":"2016","journal-title":"BMC Bioinf."},{"key":"2023070504591867500_B11","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1093\/bioinformatics\/btaa242","article-title":"CScape-somatic: distinguishing driver and passenger point mutations in the cancer genome","volume":"36","author":"Rogers","year":"2020","journal-title":"Bioinform."},{"key":"2023070504591867500_B12","doi-asserted-by":"crossref","first-page":"W315","DOI":"10.1093\/nar\/gkz350","article-title":"AlloDriver: a method for the identification and analysis of cancer driver targets","volume":"47","author":"Song","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B13","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12859-022-04788-7","article-title":"DriverRWH: discovering cancer driver genes by random walk on a gene mutation hypergraph","volume":"23","author":"Wang","year":"2022","journal-title":"BMC Bioinform."},{"key":"2023070504591867500_B14","first-page":"D394","article-title":"Unraveling allosteric landscapes of allosterome with ASD","volume":"48","author":"Liu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B15","doi-asserted-by":"crossref","first-page":"e1004966","DOI":"10.1371\/journal.pcbi.1004966","article-title":"Allostery: an overview of its history, concepts, methods, and applications","volume":"12","author":"Liu","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"2023070504591867500_B16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.drudis.2019.10.006","article-title":"Emergence of allosteric drug-resistance mutations: new challenges for allosteric drug discovery","volume":"25","author":"Lu","year":"2020","journal-title":"Drug Discov. Today"},{"key":"2023070504591867500_B17","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1021\/acs.biochem.6b00783","article-title":"Toward allosterically increased catalytic activity of insulin-degrading enzyme against amyloid peptides","volume":"56","author":"Kurochkin","year":"2017","journal-title":"Biochemistry"},{"key":"2023070504591867500_B18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2016.09.020","article-title":"Proteome-scale investigation of protein allosteric regulation perturbed by somatic mutations in 7,000 cancer genomes","volume":"100","author":"Shen","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2023070504591867500_B19","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1016\/j.jmb.2019.07.012","article-title":"On the allosteric effect of nsSNPs and the emerging importance of allosteric polymorphism","volume":"431","author":"Tee","year":"2019","journal-title":"J. Mol. Biol."},{"key":"2023070504591867500_B20","doi-asserted-by":"crossref","first-page":"167569","DOI":"10.1016\/j.jmb.2022.167569","article-title":"Allostery: allosteric cancer drivers and innovative allosteric drugs","volume":"434","author":"Nussinov","year":"2022","journal-title":"J. Mol. Biol."},{"key":"2023070504591867500_B21","doi-asserted-by":"crossref","first-page":"110522","DOI":"10.1016\/j.celrep.2022.110522","article-title":"A hotspot mutation targeting the R-RAS2 GTPase acts as a potent oncogenic driver in a wide spectrum of tumors","volume":"38","author":"Fern\u00e1ndez-Pisonero","year":"2022","journal-title":"Cell Rep."},{"key":"2023070504591867500_B22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B23","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1093\/bioinformatics\/btt399","article-title":"Allosite: a method for predicting allosteric sites","volume":"29","author":"Huang","year":"2013","journal-title":"Bioinformatics"},{"key":"2023070504591867500_B24","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B25","doi-asserted-by":"crossref","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The reactome pathway knowledgebase 2022","volume":"50","author":"Gillespie","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B26","doi-asserted-by":"crossref","first-page":"D901","DOI":"10.1093\/nar\/gkm958","article-title":"DrugBank: a knowledgebase for drugs, drug actions and drug targets","volume":"36","author":"Wishart","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B27","doi-asserted-by":"crossref","first-page":"D930","DOI":"10.1093\/nar\/gky1075","article-title":"ChEMBL: towards direct deposition of bioassay data","volume":"47","author":"Mendez","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2023070504591867500_B28","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","article-title":"NTRK fusion-positive cancers and TRK inhibitor therapy","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2023070504591867500_B29","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41379-021-00913-8","article-title":"NTRK insights: best practices for pathologists","volume":"35","author":"Hechtman","year":"2022","journal-title":"Mod. Pathol."},{"key":"2023070504591867500_B30","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1021\/acs.jmedchem.0c02076","article-title":"Structure- and similarity-based survey of allosteric kinase inhibitors, activators, and closely related compounds","volume":"65","author":"Laufk\u00f6tter","year":"2022","journal-title":"J. Med. Chem."},{"key":"2023070504591867500_B31","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.cell.2018.07.034","article-title":"Comprehensive characterization of cancer driver genes and mutations","volume":"174","author":"Bailey","year":"2018","journal-title":"Cell"},{"key":"2023070504591867500_B32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nbt.3391","article-title":"Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity","volume":"34","author":"Chang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2023070504591867500_B33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/W1\/W129\/50736624\/gkad295.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/51\/W1\/W129\/50736624\/gkad295.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T10:00:12Z","timestamp":1688551212000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/51\/W1\/W129\/7132339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":33,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2023,4,20]]},"published-print":{"date-parts":[[2023,7,5]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkad295","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7,5]]},"published":{"date-parts":[[2023,4,20]]}}}