{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:29:58Z","timestamp":1743064198868,"version":"3.37.3"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"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":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA223498","R01CA189532"],"award-info":[{"award-number":["R01CA223498","R01CA189532"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005895","name":"Fred Hutch","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"ORIP","doi-asserted-by":"publisher","award":["S10OD028685"],"award-info":[{"award-number":["S10OD028685"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Cancer is a highly heterogeneous disease, and virtually all types of cancer have subtypes. Understanding the association between cancer subtypes and genetic variations is fundamental to the development of targeted therapies for patients. Somatic mutation plays important roles in tumor development and has emerged as a new type of genetic variations for studying the association with cancer subtypes. However, the low prevalence of individual mutations poses a tremendous challenge to the related statistical analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this article, we propose an approach, subtype analysis with somatic mutations (SASOM), for the association analysis of cancer subtypes with somatic mutations. Our approach tests the association between a set of somatic mutations (from a genetic pathway) and subtypes, while incorporating functional information of the mutations into the analysis. We further propose a robust p-value combination procedure, DAPC, to synthesize statistical significance from different sources. Simulation studies show that the proposed approach has correct type I error and tends to be more powerful than possible alternative methods. In a real data application, we examine the somatic mutations from a cutaneous melanoma dataset, and identify a genetic pathway that is associated with immune-related subtypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The SASOM R package is available at https:\/\/github.com\/rksyouyou\/SASOM-pkg. R scripts and data are available at https:\/\/github.com\/rksyouyou\/SASOM-analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa1090","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T12:21:23Z","timestamp":1608639683000},"page":"50-56","source":"Crossref","is-referenced-by-count":8,"title":["A method for subtype analysis with somatic mutations"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-1506","authenticated-orcid":false,"given":"Meiling","family":"Liu","sequence":"first","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Wright State University , Dayton, OH 45435, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C","family":"Wu","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Hsu","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianchuan","family":"He","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"2024041009302366600_btaa1090-B1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10555-018-09775-0","article-title":"Cancer-associated mucins: role in immune modulation and metastasis","volume":"38","author":"Bhatia","year":"2019","journal-title":"Cancer Metas. Rev"},{"key":"2024041009302366600_btaa1090-B2","doi-asserted-by":"crossref","first-page":"17014","DOI":"10.18632\/oncotarget.24795","article-title":"Molecular signatures associated with tumor-specific immune response in melanoma patients treated with dendritic cell-based immunotherapy","volume":"9","author":"Garc\u00eda-Salum","year":"2018","journal-title":"Oncotarget"},{"key":"2024041009302366600_btaa1090-B3","first-page":"1","article-title":"The prognostic effects of somatic mutations in er-positive breast cancer","volume":"9","author":"Griffith","year":"2018","journal-title":"Nat. Commun"},{"key":"2024041009302366600_btaa1090-B4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/biom.12745","article-title":"Multivariate association analysis with somatic mutation data","volume":"74","author":"He","year":"2018","journal-title":"Biometrics"},{"key":"2024041009302366600_btaa1090-B5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/biomet\/asx076","article-title":"Choosing between methods of combining-values","volume":"105","author":"Heard","year":"2018","journal-title":"Biometrika"},{"key":"2024041009302366600_btaa1090-B6","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1002\/sim.7034","article-title":"Semi-varying coefficient multinomial logistic regression for disease progression risk prediction","volume":"35","author":"Ke","year":"2016","journal-title":"Stat. Med"},{"key":"2024041009302366600_btaa1090-B7","doi-asserted-by":"crossref","first-page":"D985","DOI":"10.1093\/nar\/gkw1055","article-title":"Open targets: a platform for therapeutic target identification and validation","volume":"45","author":"Koscielny","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2024041009302366600_btaa1090-B8","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1101\/gr.118992.110","article-title":"Prioritizing candidate disease genes by network-based boosting of genome-wide association data","volume":"21","author":"Lee","year":"2011","journal-title":"Genome Res"},{"key":"2024041009302366600_btaa1090-B9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The molecular signatures database hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"2024041009302366600_btaa1090-B10","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.18632\/oncotarget.26773","article-title":"A global immune gene expression signature for human cancers","volume":"10","author":"Liu","year":"2019","journal-title":"Oncotarget"},{"key":"2024041009302366600_btaa1090-B11","doi-asserted-by":"crossref","first-page":"e1007746","DOI":"10.1371\/journal.pgen.1007746","article-title":"Association analysis using somatic mutations","volume":"14","author":"Liu","year":"2018","journal-title":"PLoS Genet"},{"key":"2024041009302366600_btaa1090-B12","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1126\/science.aab4082","article-title":"Somatic mutation in cancer and normal cells","volume":"349","author":"Martincorena","year":"2015","journal-title":"Science"},{"key":"2024041009302366600_btaa1090-B13","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00357-014-9161-z","article-title":"Ward\u00e2s hierarchical agglomerative clustering method: which algorithms implement ward\u00e2s criterion?","volume":"31","author":"Murtagh","year":"2014","journal-title":"J. Class"},{"key":"2024041009302366600_btaa1090-B14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1158\/1055-9965.EPI-13-0463","article-title":"Breast cancer subtypes and previously established genetic risk factors: a Bayesian approach","volume":"23","author":"O'Brien","year":"2014","journal-title":"Cancer Epidemiol. Prev. Biomarkers"},{"key":"2024041009302366600_btaa1090-B15","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/0014-5793(95)00777-7","article-title":"Molecular cloning and sequence analysis of human preprocathepsin C","volume":"369","author":"Pari\u0161","year":"1995","journal-title":"FEBS Lett"},{"key":"2024041009302366600_btaa1090-B16","doi-asserted-by":"crossref","first-page":"vi19","DOI":"10.1093\/annonc\/mds190","article-title":"Pathological and molecular diagnosis of triple-negative breast cancer: a clinical perspective","volume":"23","author":"Penault-Llorca","year":"2012","journal-title":"Ann. Oncol"},{"first-page":"229","year":"2014","author":"Pio","key":"2024041009302366600_btaa1090-B17"},{"key":"2024041009302366600_btaa1090-B18","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1074\/jbc.272.15.10260","article-title":"Human dipeptidyl-peptidase I. Gene characterization, localization, and expression","volume":"272","author":"Rao","year":"1997","journal-title":"J. Biol. Chem"},{"key":"2024041009302366600_btaa1090-B19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1042\/bj2490593","article-title":"The complete amino acid sequence of human complement factor H","volume":"249","author":"Ripoche","year":"1988","journal-title":"Biochem. J"},{"key":"2024041009302366600_btaa1090-B20","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/gepi.21717","article-title":"A unified mixed-effects model for rare-variant association in sequencing studies","volume":"37","author":"Sun","year":"2013","journal-title":"Genet. Epidemiol"},{"key":"2024041009302366600_btaa1090-B21","first-page":"25","article-title":"Network-constrained group lasso for high-dimensional multinomial classification with application to cancer subtype prediction","volume":"13","author":"Tian","year":"2014","journal-title":"Cancer Inform"},{"key":"2024041009302366600_btaa1090-B22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.csda.2014.09.009","article-title":"Variable selection in general multinomial logit models","volume":"82","author":"Tutz","year":"2015","journal-title":"Comput. Stat. Data Anal"},{"key":"2024041009302366600_btaa1090-B23","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1002\/sim.8666","article-title":"Multinomial logistic regression with missing outcome data: an application to cancer subtypes","volume":"39","author":"Wang","year":"2020","journal-title":"Stat. Med"},{"key":"2024041009302366600_btaa1090-B24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","article-title":"Rare-variant association testing for sequencing data with the sequence kernel association test","volume":"89","author":"Wu","year":"2011","journal-title":"Am. J. Hum. Genet"},{"key":"2024041009302366600_btaa1090-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2011\/210813","article-title":"Histopathological variants of cutaneous squamous cell carcinoma: a review","volume":"2011","author":"Yanofsky","year":"2011","journal-title":"J. Skin Cancer"},{"key":"2024041009302366600_btaa1090-B26","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10238-020-00619-2","article-title":"Muc4 isoforms expression profiling and prognosis value in Chinese melanoma patients","volume":"20","author":"Yu","year":"2020","journal-title":"Clin. Exp. Med"},{"key":"2024041009302366600_btaa1090-B27","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1534\/genetics.116.199646","article-title":"Powerful genetic association analysis for common or rare variants with high-dimensional structured traits","volume":"206","author":"Zhan","year":"2017","journal-title":"Genetics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa1090\/36122488\/btaa1090.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/1\/50\/57195867\/btaa1090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/1\/50\/57195867\/btaa1090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T09:38:34Z","timestamp":1712741914000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/1\/50\/6069547"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,4,9]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa1090","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2021,1,1]]}}}