{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:00:45Z","timestamp":1772521245304,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21CA216452"],"award-info":[{"award-number":["R21CA216452"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004897","name":"Pennsylvania Department of Health","doi-asserted-by":"publisher","award":["GBMF4554"],"award-info":[{"award-number":["GBMF4554"]}],"id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004897","name":"Pennsylvania Department of Health","doi-asserted-by":"publisher","award":["#4100070287"],"award-info":[{"award-number":["#4100070287"]}],"id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004897","name":"The Pennsylvania Department of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004897","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Extreme Science and Engineering Discovery Environment"},{"name":"XSEDE"},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OCI-1053575"],"award-info":[{"award-number":["OCI-1053575"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"NSF","doi-asserted-by":"publisher","award":["ACI-1445606"],"award-info":[{"award-number":["ACI-1445606"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pittsburgh Supercomputing Center"},{"DOI":"10.13039\/100008538","name":"PSC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"NHGRI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Phylogenetic reconstruction of tumor evolution has emerged as a crucial tool for making sense of the complexity of emerging cancer genomic datasets. Despite the growing use of phylogenetics in cancer studies, though, the field has only slowly adapted to many ways that tumor evolution differs from classic species evolution. One crucial question in that regard is how to handle inference of structural variations (SVs), which are a major mechanism of evolution in cancers but have been largely neglected in tumor phylogenetics to date, in part due to the challenges of reliably detecting and typing SVs and interpreting them phylogenetically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present a novel method for reconstructing evolutionary trajectories of SVs from bulk whole-genome sequence data via joint deconvolution and phylogenetics, to infer clonal sub-populations and reconstruct their ancestry. We establish a novel likelihood model for joint deconvolution and phylogenetic inference on bulk SV data and formulate an associated optimization algorithm. We demonstrate the approach to be efficient and accurate for realistic scenarios of SV mutation on simulated data. Application to breast cancer genomic data from The Cancer Genome Atlas shows it to be practical and effective at reconstructing features of SV-driven evolution in single tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Python source code and associated documentation are available at https:\/\/github.com\/jaebird123\/tusv.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty270","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T02:58:15Z","timestamp":1523588295000},"page":"i357-i365","source":"Crossref","is-referenced-by-count":47,"title":["Deconvolution and phylogeny inference of structural variations in tumor genomic samples"],"prefix":"10.1093","volume":"34","author":[{"given":"Jesse","family":"Eaton","sequence":"first","affiliation":[{"name":"Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA"}]},{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA, USA"},{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"2023051604232706600_bty270-B1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2013.11.014","article-title":"Mutational signatures: the patterns of somatic mutations hidden in cancer genomes","volume":"24","author":"Alexandrov","year":"2014","journal-title":"Curr. Opin. Genet. Dev"},{"key":"2023051604232706600_bty270-B2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/sysbio\/syu081","article-title":"Cancer evolution: mathematical models and computational inference","volume":"64","author":"Beerenwinkel","year":"2015","journal-title":"Syst. Biol"},{"key":"2023051604232706600_bty270-B3","doi-asserted-by":"crossref","first-page":"i258","DOI":"10.1093\/bioinformatics\/btv233","article-title":"Inferring models of multiscale copy number evolution for single-tumor phylogenetics","volume":"31","author":"Chowdhury","year":"2015","journal-title":"Bioinformatics"},{"key":"2023051604232706600_bty270-B4","doi-asserted-by":"crossref","first-page":"i189","DOI":"10.1093\/bioinformatics\/btt205","article-title":"Phylogenetic analysis of multiprobe fluorescence in situ hybridization data from tumor cell populations","volume":"29","author":"Chowdhury","year":"2013","journal-title":"Bioinformatics"},{"key":"2023051604232706600_bty270-B5","doi-asserted-by":"crossref","first-page":"e1003740.","DOI":"10.1371\/journal.pcbi.1003740","article-title":"Algorithms to model single gene, single chromosome, and whole genome copy number changes jointly in tumor phylogenetics","volume":"10","author":"Chowdhury","year":"2014","journal-title":"PLoS Comput. Biol"},{"key":"2023051604232706600_bty270-B6","doi-asserted-by":"crossref","first-page":"35.","DOI":"10.1186\/s13059-015-0602-8","article-title":"PhyloWGS: reconstructing subclonal composition and evolution from whole-genome sequencing of tumors","volume":"16","author":"Deshwar","year":"2015","journal-title":"Genome Biol"},{"key":"2023051604232706600_bty270-B7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/cmb.1999.6.37","article-title":"Inferring tree models of oncogenesis from comparative genomic hybridization data","volume":"6","author":"Desper","year":"1999","journal-title":"J. Comput. Biol"},{"key":"2023051604232706600_bty270-B8","doi-asserted-by":"crossref","first-page":"i62","DOI":"10.1093\/bioinformatics\/btv261","article-title":"Reconstruction of clonal trees and tumor composition from multi-sample sequencing data","volume":"33","author":"El-Kebir","year":"2015","journal-title":"Bioinformatics"},{"key":"2023051604232706600_bty270-B9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cels.2016.07.004","article-title":"Inferring the mutational history of a tumor using multi-state perfect phylogeny mixtures","volume":"3","author":"El-Kebir","year":"2016","journal-title":"Cell Syst"},{"key":"2023051604232706600_bty270-B10","doi-asserted-by":"crossref","first-page":"13.","DOI":"10.1186\/s13015-017-0103-2","article-title":"Complexity and algorithms for copy-number evolution problems","volume":"12","author":"El-Kebir","year":"2017","journal-title":"Algorithms Mol. Biol"},{"key":"2023051604232706600_bty270-B11","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"2023051604232706600_bty270-B12","doi-asserted-by":"crossref","first-page":"96.","DOI":"10.1186\/s13059-016-0936-x","article-title":"Tree inference for single-cell data","volume":"17","author":"Jahn","year":"2016","journal-title":"Genome Biol"},{"key":"2023051604232706600_bty270-B13","doi-asserted-by":"crossref","first-page":"201522203","DOI":"10.1073\/pnas.1522203113","article-title":"Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing","volume":"113","author":"Jiang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051604232706600_bty270-B14","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1002\/ijc.24148","article-title":"The clonal evolution of metastases from primary serous epithelial ovarian cancers","volume":"124","author":"Khalique","year":"2009","journal-title":"Int. J. Cancer"},{"key":"2023051604232706600_bty270-B15","first-page":"21","article-title":"Allele-specific quantification of structural variations in cancer genomes","volume":"3","author":"Li","year":"2016","journal-title":"Cell"},{"key":"2023051604232706600_bty270-B16","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/ng1768","article-title":"Genetic clonal diversity predicts progression to esophageal adenocarcinoma","volume":"38","author":"Maley","year":"2006","journal-title":"Nat. Genet"},{"key":"2023051604232706600_bty270-B17","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1093\/bioinformatics\/btv003","article-title":"Clonality inference in multiple tumor samples using phylogeny","volume":"31","author":"Malikic","year":"2015","journal-title":"Bioinformatics"},{"key":"2023051604232706600_bty270-B18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbcan.2009.11.002","article-title":"Tumor heterogeneity: causes and consequences","volume":"1805","author":"Marusyk","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"2023051604232706600_bty270-B19","doi-asserted-by":"crossref","first-page":"283ra54.","DOI":"10.1126\/scitranslmed.aaa1408","article-title":"Clonal status of actionable driver events and the timing of mutational processes in cancer evolution","volume":"7","author":"McGranahan","year":"2015","journal-title":"Sci. Transl. Med"},{"key":"2023051604232706600_bty270-B20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The clonal evolution of tumor cell populations","volume":"194","author":"Nowell","year":"1976","journal-title":"Science"},{"key":"2023051604232706600_bty270-B21","first-page":"3532","volume-title":"Bioinformatics","author":"Oesper","year":"2014"},{"key":"2023051604232706600_bty270-B22","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1142\/S021972000700259X","article-title":"Reconstructing tumor phylogenies from heterogeneous single-cell data","volume":"05","author":"Pennington","year":"2007","journal-title":"J. Bioinform. Comput. Biol"},{"key":"2023051604232706600_bty270-B23","doi-asserted-by":"crossref","first-page":"91.","DOI":"10.1186\/s13059-015-0647-8","article-title":"Fast and scalable inference of multi-sample cancer lineages","volume":"16","author":"Popic","year":"2015","journal-title":"Genome Biol"},{"key":"2023051604232706600_bty270-B24","doi-asserted-by":"crossref","first-page":"69.","DOI":"10.1186\/s13059-016-0929-9","article-title":"Onconem: inferring tumor evolution from single-cell sequencing data","volume":"17","author":"Ross","year":"2016","journal-title":"Genome Biol"},{"key":"2023051604232706600_bty270-B25","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nmeth.2883","article-title":"Pyclone: statistical inference of clonal population structure in cancer","volume":"11","author":"Roth","year":"2014","journal-title":"Nat. Meth"},{"key":"2023051604232706600_bty270-B26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrg.2016.170","article-title":"The evolution of tumour phylogenetics: principles and practice","volume":"18","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Genet"},{"key":"2023051604232706600_bty270-B27","doi-asserted-by":"crossref","first-page":"42.","DOI":"10.1186\/1471-2105-11-42","article-title":"Applying unmixing to gene expression data for tumor phylogeny inference","volume":"11","author":"Schwartz","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023051604232706600_bty270-B28","doi-asserted-by":"crossref","first-page":"e1003535.","DOI":"10.1371\/journal.pcbi.1003535","article-title":"Phylogenetic quantification of intra-tumour heterogeneity","volume":"10","author":"Schwarz","year":"2014","journal-title":"PLoS Comput. Biol"},{"key":"2023051604232706600_bty270-B29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"The Cancer Genome Atlas Network","year":"2012","journal-title":"Nature"},{"key":"2023051604232706600_bty270-B30","doi-asserted-by":"crossref","first-page":"i106","DOI":"10.1093\/bioinformatics\/btq213","article-title":"Robust unmixing of tumor states in array comparative genomic hybridization data","volume":"26","author":"Tolliver","year":"2010","journal-title":"Bioinformatics"},{"key":"2023051604232706600_bty270-B31","first-page":"318","article-title":"The copy number tree mixture deconvolution problem and applications to multi-sample bulk sequencing tumor data","volume-title":"Proc. International Conference on Research in Computational Molecular Biology (RECOMB)","author":"Zaccaria","year":"2017"},{"key":"2023051604232706600_bty270-B32","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ng.2760","article-title":"Pan-cancer patterns of somatic copy number alteration","volume":"45","author":"Zack","year":"2013","journal-title":"Nat. Genet"},{"key":"2023051604232706600_bty270-B33","doi-asserted-by":"crossref","first-page":"178.","DOI":"10.1186\/s13059-017-1311-2","article-title":"Sifit: inferring tumor trees from single-cell sequencing data under finite-sites models","volume":"18","author":"Zafar","year":"2017","journal-title":"Genome Biol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/13\/i357\/50315874\/bioinformatics_34_13_i357.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/13\/i357\/50315874\/bioinformatics_34_13_i357.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:25:19Z","timestamp":1684196719000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/34\/13\/i357\/5045780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,27]]},"references-count":33,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2018,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bty270","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/257014","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,7,1]]},"published":{"date-parts":[[2018,6,27]]}}}