{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:23:39Z","timestamp":1780957419799,"version":"3.54.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Binary (or Boolean) matrices provide a common effective data representation adopted in several domains of computational biology, especially for investigating cancer and other human diseases. For instance, they are used to summarize genetic aberrations\u2014copy number alterations or mutations\u2014observed in cancer patient cohorts, effectively highlighting combinatorial relations among them. One of these is the tendency for two or more genes not to be co-mutated in the same sample or patient, i.e. a mutual-exclusivity trend. Exploiting this principle has allowed identifying new cancer driver protein-interaction networks and has been proposed to design effective combinatorial anti-cancer therapies rationally. Several tools exist to identify and statistically assess mutual-exclusive cancer-driver genomic events. However, these tools need to be equipped with robust\/efficient methods to sort rows and columns of a binary matrix to visually highlight possible mutual-exclusivity trends.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we formalize the mutual-exclusivity-sorting problem and present MutExMatSorting: an R package implementing a computationally efficient algorithm able to sort rows and columns of a binary matrix to highlight mutual-exclusivity patterns. Particularly, our algorithm minimizes the extent of collective vertical overlap between consecutive non-zero entries across rows while maximizing the number of adjacent non-zero entries in the same row. Here, we demonstrate that existing tools for mutual-exclusivity analysis are suboptimal according to these criteria and are outperformed by MutExMatSorting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/AleVin1995\/MutExMatSorting.<\/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\/btad016","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T17:42:02Z","timestamp":1673545322000},"source":"Crossref","is-referenced-by-count":3,"title":["A heuristic algorithm solving the mutual-exclusivity-sorting problem"],"prefix":"10.1093","volume":"39","author":[{"given":"Alessandro","family":"Vinceti","sequence":"first","affiliation":[{"name":"Computational Biology Research Centre, Human Technopole , 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Trastulla","sequence":"additional","affiliation":[{"name":"Computational Biology Research Centre, Human Technopole , 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Perron","sequence":"additional","affiliation":[{"name":"Computational Biology Research Centre, Human Technopole , 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-8794","authenticated-orcid":false,"given":"Andrea","family":"Raiconi","sequence":"additional","affiliation":[{"name":"Institute for Applied Mathematics \u201cMauro Picone\u201d, National Research Council (IAC-CNR) , 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-8913","authenticated-orcid":false,"given":"Francesco","family":"Iorio","sequence":"additional","affiliation":[{"name":"Computational Biology Research Centre, Human Technopole , 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"2023012019094261300_btad016-B1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"2023012019094261300_btad016-B2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/modpathol.2013.144","article-title":"ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas","volume":"27","author":"Allo","year":"2014","journal-title":"Mod. Pathol"},{"key":"2023012019094261300_btad016-B3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41586-019-1103-9","article-title":"Prioritisation of cancer therapeutic targets using CRISPR-Cas9 screens","volume":"568","author":"Behan","year":"2019","journal-title":"Nature"},{"key":"2023012019094261300_btad016-B25","volume-title":"A Block-Sorting Lossless Data Compression Algorithm","author":"Burrows","year":"1994"},{"key":"2023012019094261300_btad016-B4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The Cancer Genome Atlas Pan-Cancer analysis project","volume":"45","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nat. Genet"},{"key":"2023012019094261300_btad016-B5","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"2023012019094261300_btad016-B6","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1101\/gr.125567.111","article-title":"Mutual exclusivity analysis identifies oncogenic network modules","volume":"22","author":"Ciriello","year":"2012","journal-title":"Genome Res"},{"issue":"Unit 8.17","key":"2023012019094261300_btad016-B7","article-title":"Using MEMo to discover mutual exclusivity modules in cancer","volume":"Chapter, 8","author":"Ciriello","year":"2013","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"2023012019094261300_btad016-B8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.drudis.2013.10.012","article-title":"Big data in biomedicine","volume":"19","author":"Costa","year":"2014","journal-title":"Drug Discov. Today"},{"key":"2023012019094261300_btad016-B9","doi-asserted-by":"crossref","DOI":"10.1002\/0471200611","volume-title":"Elements of Information Theory","author":"Cover","year":"1991"},{"key":"2023012019094261300_btad016-B10","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1038\/s41467-019-13805-y","article-title":"Agreement between two large pan-cancer genome-scale CRISPR knock-out datasets","volume":"10","author":"Dempster","year":"2019","journal-title":"Nat. Commun"},{"key":"2023012019094261300_btad016-B11","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz984","article-title":"The ProteomeXchange consortium in 2020: enabling \u2018big data\u2019 approaches in proteomics","author":"Deutsch","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023012019094261300_btad016-B12","doi-asserted-by":"crossref","first-page":"D1365","DOI":"10.1093\/nar\/gkaa882","article-title":"Project Score database: a resource for investigating cancer cell dependencies and prioritising therapeutic targets","volume":"49","author":"Dwane","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2023012019094261300_btad016-B13","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.trecan.2021.04.009","article-title":"Co-occurrence and mutual exclusivity: what cross-cancer mutation patterns can tell us","volume":"7","author":"El Tekle","year":"2021","journal-title":"Trends Cancer Res"},{"key":"2023012019094261300_btad016-B14","doi-asserted-by":"crossref","first-page":"i617","DOI":"10.1093\/bioinformatics\/btu474","article-title":"Fast randomisation of large genomic datasets while preserving alteration counts","volume":"30","author":"Gobbi","year":"2014","journal-title":"Bioinformatics"},{"key":"2023012019094261300_btad016-B15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/WCO.0000000000000795","article-title":"Data science in neurodegenerative disease: its capabilities, limitations, and perspectives","volume":"33","author":"Golriz Khatami","year":"2020","journal-title":"Curr. Opin. Neurol"},{"key":"2023012019094261300_btad016-B16","doi-asserted-by":"crossref","first-page":"6718","DOI":"10.1158\/0008-5472.CAN-11-1562","article-title":"ARID1A, a factor that promotes formation of SWI\/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers","volume":"71","author":"Guan","year":"2011","journal-title":"Cancer Res"},{"key":"2023012019094261300_btad016-B17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nm.3480","article-title":"ARID1B is a specific vulnerability in ARID1A-mutant cancers","volume":"20","author":"Helming","year":"2014","journal-title":"Nat. Med"},{"key":"2023012019094261300_btad016-B18","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1073\/pnas.1316793111","article-title":"Functional epigenetics approach identifies BRM\/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers","volume":"111","author":"Hoffman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023012019094261300_btad016-B19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cell.2016.06.017","article-title":"A landscape of pharmacogenomic interactions in cancer","volume":"166","author":"Iorio","year":"2016","journal-title":"Cell"},{"key":"2023012019094261300_btad016-B20","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1186\/s12859-016-1402-1","article-title":"Efficient randomisation of biological networks while preserving functional characterisation of individual nodes","volume":"17","author":"Iorio","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2023012019094261300_btad016-B21","doi-asserted-by":"crossref","first-page":"6713","DOI":"10.1038\/s41598-018-25076-6","article-title":"Pathway-based dissection of the genomic heterogeneity of cancer hallmarks\u2019 acquisition with SLAPenrich","volume":"8","author":"Iorio","year":"2018","journal-title":"Sci. Rep"},{"key":"2023012019094261300_btad016-B22","first-page":"13","author":"Johnson","year":"2004"},{"key":"2023012019094261300_btad016-B23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.lungcan.2019.01.003","article-title":"Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11","volume":"130","author":"La Fleur","year":"2019","journal-title":"Lung Cancer"},{"key":"2023012019094261300_btad016-B24","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.aam7344","article-title":"PARP inhibitors: synthetic lethality in the clinic","volume":"355","author":"Lord","year":"2017","journal-title":"Science"},{"key":"2023012019094261300_btad016-B26","volume-title":"Information-Theoretic Variable Selection and Network Inference from Microarray Data","author":"Meyer","year":"2008"},{"key":"2023012019094261300_btad016-B27","doi-asserted-by":"crossref","DOI":"10.1038\/ng.3984","article-title":"Computational correction of copy number effect improves specificity of CRISPR\u2013Cas9 essentiality screens in cancer cells","volume":"49","author":"Meyers","year":"2017","journal-title":"Nature Genetics"},{"key":"2023012019094261300_btad016-B28","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrd.2017.190","article-title":"Synthetic lethality screens point the way to new cancer drug targets","volume":"16","author":"Mullard","year":"2017","journal-title":"Nat. Rev. Drug Discov"},{"key":"2023012019094261300_btad016-B29","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.cels.2020.04.007","article-title":"CELLector: genomics-guided selection of cancer in vitro models","volume":"10","author":"Najgebauer","year":"2020","journal-title":"Cell Syst"},{"key":"2023012019094261300_btad016-B30","first-page":"763","article-title":"The genome as a record of environmental exposure","volume":"30","author":"Nik-Zainal","year":"2015","journal-title":"Mutagenesis"},{"key":"2023012019094261300_btad016-B31","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrg.2017.47","article-title":"Synthetic lethality and cancer","volume":"18","author":"O\u2019Neil","year":"2017","journal-title":"Nat. Rev. Genet"},{"key":"2023012019094261300_btad016-B32","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1038\/s41467-019-11461-w","article-title":"Quantifying the impact of public omics data","volume":"10","author":"Perez-Riverol","year":"2019","journal-title":"Nat. Commun"},{"key":"2023012019094261300_btad016-B33","doi-asserted-by":"crossref","first-page":"e1009986","DOI":"10.1371\/journal.pgen.1009986","article-title":"Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis","volume":"17","author":"Reske","year":"2021","journal-title":"PLoS Genet"},{"key":"2023012019094261300_btad016-B34","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1038\/onc.2015.375","article-title":"Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma","volume":"35","author":"Schabath","year":"2016","journal-title":"Oncogene"},{"key":"2023012019094261300_btad016-B35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13062-015-0086-1","article-title":"Inferring synthetic lethal interactions from mutual exclusivity of genetic events in cancer","volume":"10","author":"Srihari","year":"2015","journal-title":"Biol. Direct"},{"key":"2023012019094261300_btad016-B36","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","article-title":"Defining a cancer dependency map","volume":"170","author":"Tsherniak","year":"2017","journal-title":"Cell"},{"key":"2023012019094261300_btad016-B37","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1101\/gr.120477.111","article-title":"De novo discovery of mutated driver pathways in cancer","volume":"22","author":"Vandin","year":"2012","journal-title":"Genome Res"},{"key":"2023012019094261300_btad016-B38","article-title":"SynLethDB 2.0: a web-based knowledge graph database on synthetic lethality for novel anti-cancer drug discovery","volume":"2022, baac030","author":"Wang","year":"2022","journal-title":"Database"},{"key":"2023012019094261300_btad016-B39","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrg3539","article-title":"Emerging patterns of somatic mutations in cancer","volume":"14","author":"Watson","year":"2013","journal-title":"Nat. Rev. Genet"},{"key":"2023012019094261300_btad016-B40","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.aca.2020.10.038","article-title":"Multi-omics integration in biomedical research \u2013 a metabolomics-centric review","volume":"1141","author":"W\u00f6rheide","year":"2021","journal-title":"Anal. Chim. Acta"},{"key":"2023012019094261300_btad016-B41","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1080\/15384101.2017.1377503","article-title":"Harnessing mutual exclusivity between TP53 and ARID1 a mutations","volume":"16","author":"Wu","year":"2017","journal-title":"Cell Cycle"},{"key":"2023012019094261300_btad016-B42","doi-asserted-by":"crossref","first-page":"745187","DOI":"10.3389\/fonc.2021.745187","article-title":"The role of ARID1A in tumors: tumor initiation or tumor suppression?","volume":"11","author":"Xu","year":"2021","journal-title":"Front. Oncol"},{"key":"2023012019094261300_btad016-B43","doi-asserted-by":"crossref","first-page":"bar026","DOI":"10.1093\/database\/bar026","article-title":"International Cancer Genome Consortium Data Portal\u2014a one-stop shop for cancer genomics data","volume":"2011","author":"Zhang","year":"2011","journal-title":"Database"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btad016\/48638251\/btad016.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/1\/btad016\/48805292\/btad016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/1\/btad016\/48805292\/btad016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T19:10:15Z","timestamp":1674241815000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btad016\/6986128"}},"subtitle":[],"editor":[{"given":"Alfonso","family":"Valencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btad016","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2023,1,1]]},"article-number":"btad016"}}