{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:10Z","timestamp":1772138050184,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM138634-01"],"award-info":[{"award-number":["R01GM138634-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Copy number alterations (CNAs) are a significant driver in cancer growth and development, but remain poorly characterized on the single cell level. Although genome evolution in cancer cells is Markovian through evolutionary time, CNAs are not Markovian along the genome. However, existing methods call copy number profiles with Hidden Markov Models or change point detection algorithms based on changes in observed read depth, corrected by genome content and do not account for the stochastic evolutionary process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present a theoretical framework to use tumor evolutionary history to accurately call CNAs in a principled manner. To model the tumor evolutionary process and account for technical noise from low coverage single-cell whole genome sequencing data, we developed SCONCE, a method based on a Hidden Markov Model to analyze read depth data from tumor cells using matched normal cells as negative controls. Using a combination of public data sets and simulations, we show SCONCE accurately decodes copy number profiles, and provides a useful tool for understanding tumor evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availabilityand implementation<\/jats:title>\n                    <jats:p>SCONCE is implemented in C++11 and is freely available from https:\/\/github.com\/NielsenBerkeleyLab\/sconce.<\/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\/btac041","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T23:12:25Z","timestamp":1643065945000},"page":"1801-1808","source":"Crossref","is-referenced-by-count":16,"title":["SCONCE: a method for profiling copy number alterations in cancer evolution using single-cell whole genome sequencing"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-6998","authenticated-orcid":false,"given":"Sandra","family":"Hui","sequence":"first","affiliation":[{"name":"Center for Computational Biology, University of California, Berkeley , Berkeley, CA 94720, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-6591","authenticated-orcid":false,"given":"Rasmus","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, University of California, Berkeley , Berkeley, CA 94720, USA"},{"name":"Department of Integrative Biology, University of California, Berkeley , Berkeley, CA 94720, USA"},{"name":"Department of Statistics, University of California, Berkeley , Berkeley, CA 94720, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"2023020109005872500_btac041-B1","year":"2018"},{"key":"2023020109005872500_btac041-B2","year":"2019"},{"key":"2023020109005872500_btac041-B3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13059-016-0971-7","article-title":"Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies","volume":"17","author":"Bakker","year":"2016","journal-title":"Genome Biol"},{"key":"2023020109005872500_btac041-B4","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/nprot.2012.039","article-title":"Genome-wide copy number analysis of single cells","volume":"7","author":"Baslan","year":"2012","journal-title":"Nat. Protoc"},{"key":"2023020109005872500_btac041-B5","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"2023020109005872500_btac041-B6","doi-asserted-by":"crossref","first-page":"e30377","DOI":"10.1371\/journal.pone.0030377","article-title":"Fast computation and applications of genome mappability","volume":"7","author":"Derrien","year":"2012","journal-title":"PLoS One"},{"key":"2023020109005872500_btac041-B7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"Dunham","year":"2012","journal-title":"Nature"},{"key":"2023020109005872500_btac041-B8","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01734359","article-title":"Journal of molecular evolution evolutionary trees from DNA sequences: a maximum likelihood approach","volume":"17","author":"Felsenstein","year":"1981","journal-title":"J. Mol. Evol"},{"key":"2023020109005872500_btac041-B9","doi-asserted-by":"crossref","DOI":"10.1002\/9781118723203","volume-title":"Practical Methods of Optimization","author":"Fletcher","year":"2000"},{"key":"2023020109005872500_btac041-B10","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/ng.3641","article-title":"Punctuated copy number evolution and clonal stasis in triple-negative breast cancer","volume":"48","author":"Gao","year":"2016","journal-title":"Nat. Genet"},{"key":"2023020109005872500_btac041-B11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-019-1907-7","article-title":"The evolutionary history of 2,658 cancers","volume":"578","author":"Gerstung","year":"2020","journal-title":"Nature"},{"key":"2023020109005872500_btac041-B12","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/s12276-020-00499-2","article-title":"Single-cell sequencing techniques from individual to multiomics analyses","volume":"52","author":"Kashima","year":"2020","journal-title":"Exp. Mol. Med"},{"key":"2023020109005872500_btac041-B13","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1101\/gr.220707.117","article-title":"Single-cell sequencing data reveal widespread recurrence and loss of mutational hits in the life histories of tumors","volume":"27","author":"Kuipers","year":"2017","journal-title":"Genome Res"},{"key":"2023020109005872500_btac041-B14","author":"Kuipers","year":"2020"},{"key":"2023020109005872500_btac041-B15","author":"Lai","year":"2019"},{"key":"2023020109005872500_btac041-B16","first-page":"522","article-title":"Comprehensive identification and characterization of somatic copy number alterations in triple-negative breast cancer","volume":"56","author":"Li","year":"2020","journal-title":"Int. J. Oncol"},{"key":"2023020109005872500_btac041-B17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13059-020-02119-8","article-title":"Methods for copy number aberration detection from single-cell DNA-sequencing data","volume":"21","author":"Mallory","year":"2020","journal-title":"Genome Biol"},{"key":"2023020109005872500_btac041-B18","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature09807","article-title":"Tumour evolution inferred by single-cell sequencing","volume":"472","author":"Navin","year":"2011","journal-title":"Nature"},{"key":"2023020109005872500_btac041-B19","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1186\/1471-2164-13-591","article-title":"Copynumber: efficient algorithms for single- and multi-track copy number segmentation","volume":"13","author":"Nilsen","year":"2012","journal-title":"BMC Genomics"},{"key":"2023020109005872500_btac041-B20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/biostatistics\/kxh008","article-title":"Circular binary segmentation for the analysis of array-based DNA copy number data","volume":"5","author":"Olshen","year":"2004","journal-title":"Biostatistics"},{"key":"2023020109005872500_btac041-B21","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"2023020109005872500_btac041-B22","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/bty1055","article-title":"ACE: absolute copy number estimation from low-coverage whole-genome sequencing data","volume":"35","author":"Poell","year":"2019","journal-title":"Bioinformatics"},{"key":"2023020109005872500_btac041-B23","first-page":"841","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023020109005872500_btac041-B24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41587-019-0364-z","article-title":"A community effort to create standards for evaluating tumor subclonal reconstruction","volume":"38","author":"Salcedo","year":"2020","journal-title":"Nat. Biotechnol"},{"key":"2023020109005872500_btac041-B25","doi-asserted-by":"crossref","first-page":"e431","DOI":"10.1093\/bioinformatics\/btl238","article-title":"Integrating copy number polymorphisms into array CGH analysis using a robust HMM","volume":"22","author":"Shah","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020109005872500_btac041-B26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-021-07686-z","article-title":"Evaluation of tools for identifying large copy number variations from ultra-low-coverage whole-genome sequencing data","volume":"22","author":"Smolander","year":"2021","journal-title":"BMC Genomics"},{"key":"2023020109005872500_btac041-B27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.molcel.2019.05.003","article-title":"Single-cell RNA sequencing in cancer: lessons learned and emerging challenges","volume":"75","author":"Suv\u00e0","year":"2019","journal-title":"Mol. Cell"},{"key":"2023020109005872500_btac041-B28","author":"Taudt","year":"2018"},{"key":"2023020109005872500_btac041-B29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev-cancerbio-030518-055609","article-title":"Deciphering human tumor biology by single-cell expression profiling","volume":"3","author":"Tirosh","year":"2019","journal-title":"Annu. Rev. Cancer Biol"},{"key":"2023020109005872500_btac041-B30","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/bioinformatics\/btl646","article-title":"A faster circular binary segmentation algorithm for the analysis of array CGH data","volume":"23","author":"Venkatraman","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020109005872500_btac041-B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18169-2","article-title":"FastClone is a probabilistic tool for deconvoluting tumor heterogeneity in bulk-sequencing samples","volume":"11","author":"Xiao","year":"2020","journal-title":"Nat. Commun"},{"key":"2023020109005872500_btac041-B32","first-page":"1396","article-title":"Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites","volume":"10","author":"Yang","year":"1993","journal-title":"Mol. Biol. Evol"},{"key":"2023020109005872500_btac041-B33","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/BF00160154","article-title":"Journal of molecular evolution maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods","volume":"39","author":"Yang","year":"1994","journal-title":"J. Mol. Evol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac041\/42394429\/btac041.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/7\/1801\/49009324\/btac041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/7\/1801\/49009324\/btac041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T15:45:12Z","timestamp":1675266312000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/38\/7\/1801\/6515610"}},"subtitle":[],"editor":[{"given":"Can","family":"Alkan","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,3,28]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btac041","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.09.23.461581","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":[[2022,4,1]]},"published":{"date-parts":[[2022,1,26]]}}}