{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:40:47Z","timestamp":1775580047513,"version":"3.50.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Research Council Synergy","award":["609883"],"award-info":[{"award-number":["609883"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Copy number alterations are driving forces of tumour development and the emergence of intra-tumour heterogeneity. A comprehensive picture of these genomic aberrations is therefore essential for the development of personalised and precise cancer diagnostics and therapies. Single-cell sequencing offers the highest resolution for copy number profiling down to the level of individual cells. Recent high-throughput protocols allow for the processing of hundreds of cells through shallow whole-genome DNA sequencing. The resulting low read-depth data poses substantial statistical and computational challenges to the identification of copy number alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We developed SCICoNE, a statistical model and MCMC algorithm tailored to single-cell copy number profiling from shallow whole-genome DNA sequencing data. SCICoNE reconstructs the history of copy number events in the tumour and uses these evolutionary relationships to identify the copy number profiles of the individual cells. We show the accuracy of this approach in evaluations on simulated data and demonstrate its practicability in applications to two breast cancer samples from different sequencing protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SCICoNE is available at https:\/\/github.com\/cbg-ethz\/SCICoNE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf072","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T07:17:40Z","timestamp":1739258260000},"source":"Crossref","is-referenced-by-count":11,"title":["Single-cell copy number calling and event history reconstruction"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-2705","authenticated-orcid":false,"given":"Jack","family":"Kuipers","sequence":"first","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Basel 4056,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Basel 4056,","place":["Switzerland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-2556","authenticated-orcid":false,"given":"Mustafa An\u0131l","family":"Tuncel","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Basel 4056,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Basel 4056,","place":["Switzerland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0559-6125","authenticated-orcid":false,"given":"Pedro F","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Basel 4056,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Basel 4056,","place":["Switzerland"]}]},{"given":"Katharina","family":"Jahn","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Basel 4056,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Basel 4056,","place":["Switzerland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-6119","authenticated-orcid":false,"given":"Niko","family":"Beerenwinkel","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Basel 4056,","place":["Switzerland"]},{"name":"SIB Swiss Institute of Bioinformatics , Basel 4056,","place":["Switzerland"]}]}],"member":"286","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"2025031206280490600_btaf072-B1","author":"10x Genomics"},{"key":"2025031206280490600_btaf072-B2","first-page":"772","article-title":"Heterogeneity and cancer","volume":"28","author":"Allison","year":"2014","journal-title":"Oncology (Williston Park)"},{"key":"2025031206280490600_btaf072-B3","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":"2025031206280490600_btaf072-B4","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41588-018-0165-1","article-title":"Genome doubling shapes the evolution and prognosis of advanced cancers","volume":"50","author":"Bielski","year":"2018","journal-title":"Nat Genet"},{"key":"2025031206280490600_btaf072-B5","doi-asserted-by":"crossref","first-page":"e1003537","DOI":"10.1371\/journal.pcbi.1003537","article-title":"BEAST 2: a software platform for Bayesian evolutionary analysis","volume":"10","author":"Bouckaert","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"2025031206280490600_btaf072-B6","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature12625","article-title":"The causes and consequences of genetic heterogeneity in cancer evolution","volume":"501","author":"Burrell","year":"2013","journal-title":"Nature"},{"key":"2025031206280490600_btaf072-B7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.trecan.2016.04.002","article-title":"Re-evaluating clonal dominance in cancer evolution","volume":"2","author":"Burrell","year":"2016","journal-title":"Trends Cancer"},{"key":"2025031206280490600_btaf072-B8","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13059-019-1645-z","article-title":"clonealign: statistical integration of independent single-cell RNA and DNA sequencing data from human cancers","volume":"20","author":"Campbell","year":"2019","journal-title":"Genome Biol"},{"key":"2025031206280490600_btaf072-B9","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":"2025031206280490600_btaf072-B10","doi-asserted-by":"crossref","first-page":"505441","DOI":"10.3389\/fgene.2020.505441","article-title":"SCCNV: a software tool for identifying copy number variation from single-cell whole-genome sequencing","volume":"11","author":"Dong","year":"2020","journal-title":"Front Genet"},{"key":"2025031206280490600_btaf072-B11","doi-asserted-by":"crossref","first-page":"1","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":"2025031206280490600_btaf072-B12","author":"Ferreira","year":"2021"},{"key":"2025031206280490600_btaf072-B13","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/nmeth.3578","article-title":"Interactive analysis and assessment of single-cell copy-number variations","volume":"12","author":"Garvin","year":"2015","journal-title":"Nat Methods"},{"key":"2025031206280490600_btaf072-B14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrg.2015.16","article-title":"Single-cell genome sequencing: current state of the science","volume":"17","author":"Gawad","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2025031206280490600_btaf072-B15","doi-asserted-by":"crossref","first-page":"e0158569","DOI":"10.1371\/journal.pone.0158569","article-title":"Fishtrees 3.0: tumor phylogenetics using a ploidy probe","volume":"11","author":"Gertz","year":"2016","journal-title":"PLoS One"},{"key":"2025031206280490600_btaf072-B16","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"2025031206280490600_btaf072-B17","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1101\/gr.137570.112","article-title":"Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer","volume":"22","author":"Ha","year":"2012","journal-title":"Genome Res"},{"key":"2025031206280490600_btaf072-B18","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1093\/annonc\/mdu247","article-title":"Activated PI3K\/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer","volume":"25","author":"Hashimoto","year":"2014","journal-title":"Ann Oncol"},{"key":"2025031206280490600_btaf072-B19","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ccell.2021.01.004","article-title":"The tumor profiler study: integrated, multi-omic, functional tumor profiling for clinical decision support","volume":"39","author":"Irmisch","year":"2021","journal-title":"Cancer Cell"},{"key":"2025031206280490600_btaf072-B20","author":"Ivanovic","year":"2024"},{"key":"2025031206280490600_btaf072-B21","doi-asserted-by":"crossref","first-page":"86","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":"2025031206280490600_btaf072-B22","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13059-022-02794-9","article-title":"MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution","volume":"23","author":"Kaufmann","year":"2022","journal-title":"Genome Biol"},{"key":"2025031206280490600_btaf072-B23","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.cell.2018.03.041","article-title":"Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing","volume":"173","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"2025031206280490600_btaf072-B24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"Koboldt","year":"2012","journal-title":"Nature"},{"key":"2025031206280490600_btaf072-B25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbcan.2017.02.001","article-title":"Advances in understanding tumour evolution through single-cell sequencing","volume":"1867","author":"Kuipers","year":"2017","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"2025031206280490600_btaf072-B26","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":"2025031206280490600_btaf072-B27","author":"Lai","year":"2016"},{"key":"2025031206280490600_btaf072-B28","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.cell.2019.10.026","article-title":"Clonal decomposition and DNA replication states defined by scaled single-cell genome sequencing","volume":"179","author":"Laks","year":"2019","journal-title":"Cell"},{"key":"2025031206280490600_btaf072-B29","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cell.2015.05.047","article-title":"Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis","volume":"162","author":"Levine","year":"2015","journal-title":"Cell"},{"key":"2025031206280490600_btaf072-B30","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13015-024-00264-4","article-title":"NestedBD: Bayesian inference of phylogenetic trees from single-cell copy number profiles under a birth-death model","volume":"19","author":"Liu","year":"2024","journal-title":"Algorithms Mol Biol"},{"key":"2025031206280490600_btaf072-B31","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":"2025031206280490600_btaf072-B32","doi-asserted-by":"crossref","first-page":"e1008012","DOI":"10.1371\/journal.pcbi.1008012","article-title":"Assessing the performance of methods for copy number aberration detection from single-cell DNA sequencing data","volume":"16","author":"Mallory","year":"2020","journal-title":"PLoS Comput Biol"},{"key":"2025031206280490600_btaf072-B33","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":"2025031206280490600_btaf072-B34","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13059-022-02693-z","article-title":"CONET: copy number event tree model of evolutionary tumor history for single-cell data","volume":"23","author":"Markowska","year":"2022","journal-title":"Genome Biol"},{"key":"2025031206280490600_btaf072-B35","first-page":"105","article-title":"Tumor heterogeneity: causes and consequences","volume":"1805","author":"Marusyk","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"2025031206280490600_btaf072-B36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ccell.2014.12.001","article-title":"Biological and therapeutic impact of intratumor heterogeneity in cancer evolution","volume":"27","author":"McGranahan","year":"2015","journal-title":"Cancer Cell"},{"key":"2025031206280490600_btaf072-B37","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/ng.3573","article-title":"Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer","volume":"48","author":"McPherson","year":"2016","journal-title":"Nat Genet"},{"key":"2025031206280490600_btaf072-B38","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1158\/1940-6207.CAPR-10-0108","article-title":"A comprehensive survey of clonal diversity measures in barrett\u2019s esophagus as biomarkers of progression to esophageal adenocarcinoma","volume":"3","author":"Merlo","year":"2010","journal-title":"Cancer Prev Res (Phila)"},{"key":"2025031206280490600_btaf072-B39","author":"MissionBio"},{"key":"2025031206280490600_btaf072-B40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.12688\/f1000research.29032.2","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"M\u00f6lder","year":"2021","journal-title":"F1000Res"},{"key":"2025031206280490600_btaf072-B41","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":"2025031206280490600_btaf072-B42","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"2025031206280490600_btaf072-B43","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":"2025031206280490600_btaf072-B44","doi-asserted-by":"crossref","first-page":"bbac264","DOI":"10.1093\/bib\/bbac264","article-title":"Resolving single-cell copy number profiling for large datasets","volume":"23","author":"Ruohan","year":"2022","journal-title":"Brief Bioinform"},{"key":"2025031206280490600_btaf072-B45","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.24072\/pcjournal.292","article-title":"Cancer phylogenetic tree inference at scale from 1000s of single cell genomes","volume":"3","author":"Salehi","year":"2023","journal-title":"Peer Commun J"},{"key":"2025031206280490600_btaf072-B46","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":"2025031206280490600_btaf072-B47","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1038\/s41467-018-07627-7","article-title":"Single-cell mutation identification via phylogenetic inference","volume":"9","author":"Singer","year":"2018","journal-title":"Nat Commun"},{"key":"2025031206280490600_btaf072-B48","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1038\/s41467-023-40378-8","article-title":"COMPASS: joint copy number and mutation phylogeny reconstruction from amplicon single-cell sequencing data","volume":"14","author":"Sollier","year":"2023","journal-title":"Nat Commun"},{"key":"2025031206280490600_btaf072-B49","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","article-title":"The COSMIC cancer gene census: describing genetic dysfunction across all human cancers","volume":"18","author":"Sondka","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"2025031206280490600_btaf072-B50","first-page":"126","article-title":"Distributions of tree comparison metrics\u2013some new results","volume":"42","author":"Steel","year":"1993","journal-title":"Syst Biol"},{"key":"2025031206280490600_btaf072-B51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"2025031206280490600_btaf072-B52","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13059-021-02291-5","article-title":"MEDALT: single-cell copy number lineage tracing enabling gene discovery","volume":"22","author":"Wang","year":"2021","journal-title":"Genome Biol"},{"key":"2025031206280490600_btaf072-B53","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.cels.2020.03.005","article-title":"SCOPE: a normalization and copy-number estimation method for single-cell DNA sequencing","volume":"10","author":"Wang","year":"2020","journal-title":"Cell Syst"},{"key":"2025031206280490600_btaf072-B54","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/bib\/bbx004","article-title":"DNA copy number profiling using single-cell sequencing","volume":"19","author":"Wang","year":"2018","journal-title":"Brief Bioinform"},{"key":"2025031206280490600_btaf072-B55","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.molcel.2015.05.005","article-title":"Advances and applications of single-cell sequencing technologies","volume":"58","author":"Wang","year":"2015","journal-title":"Mol Cell"},{"key":"2025031206280490600_btaf072-B56","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1093\/bioinformatics\/bti677","article-title":"A comparison study: applying segmentation to array CGH data for downstream analyses","volume":"21","author":"Willenbrock","year":"2005","journal-title":"Bioinformatics"},{"key":"2025031206280490600_btaf072-B57","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/nrg3317","article-title":"Evolution of the cancer genome","volume":"13","author":"Yates","year":"2012","journal-title":"Nat Rev Genet"},{"key":"2025031206280490600_btaf072-B58","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13059-015-0592-6","article-title":"BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies","volume":"16","author":"Yuan","year":"2015","journal-title":"Genome Biol"},{"key":"2025031206280490600_btaf072-B59","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41587-020-0661-6","article-title":"Characterizing allele-and haplotype-specific copy numbers in single cells with CHISEL","volume":"39","author":"Zaccaria","year":"2021","journal-title":"Nat Biotechnol"},{"key":"2025031206280490600_btaf072-B60","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.coisb.2017.11.008","article-title":"Computational approaches for inferring tumor evolution from single-cell genomic data","volume":"7","author":"Zafar","year":"2018","journal-title":"Curr Opin Syst Biol"},{"key":"2025031206280490600_btaf072-B61","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nmeth.4140","article-title":"Scalable whole-genome single-cell library preparation without preamplification","volume":"14","author":"Zahn","year":"2017","journal-title":"Nat Methods"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf072\/61869383\/btaf072.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/3\/btaf072\/61869383\/btaf072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/3\/btaf072\/61869383\/btaf072.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:28:57Z","timestamp":1741746537000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf072\/8011370"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf072","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.28.065755","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,2,13]]},"article-number":"btaf072"}}