{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:51:06Z","timestamp":1791528666393,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MacMillan Family Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Advances in single-cell whole genome sequencing enable profiling of the copy number state of thousands of cells with minimal sequencing bias across the genome. The Direct Library Preparation+ technique is a whole genome amplification-free single-cell whole genome sequencing method that achieves high throughput by fragmenting each cell\u2019s genome and ligating sequencing adapters using a modified Tn5 transposase, and sequencing to &amp;lt;0.1\u00d7 coverage. Despite recent advances in experimental approaches, data analysis of single-cell whole genome sequencing lags behind and the existing methods are not optimized for the analysis of frozen samples with variable DNA preservation. Furthermore, existing tools predominantly rely on read depth ratio in predefined genomic bins to call copy number, making whole genome duplication unidentifiable. To address this, we introduce Songbird, a single-cell whole genome sequencing copy number caller that is whole genome duplication sensitive, and outperforms existing tools both in breakpoint identification and true copy number detection. We demonstrate that Songbird is robust down to very low coverage, adaptable to a variety of genome versions (hg19, hg38, hs.1), and is extensible to other single-cell whole genome sequencing methods that rely on Tn5 tagmentation to fragment the genome.<\/jats:p>","DOI":"10.1093\/nar\/gkag960","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:56:49Z","timestamp":1790769409000},"source":"Crossref","is-referenced-by-count":0,"title":["Wavelet-based whole genome doubling aware single-cell copy number calling"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2550-9380","authenticated-orcid":false,"given":"Benjamin K","family":"Wesley","sequence":"first","affiliation":[{"name":"Irving Institute for Cancer Dynamics, Columbia University , Room 601 Schermerhorn Hall, 1190 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]},{"name":"Department of Biological Sciences, Columbia University, Room 600 Sherman Fairchild Center , 1212 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Wos","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren","family":"Germer","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade E B","family":"Carter","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silas","family":"Maniatis","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0010-4251","authenticated-orcid":false,"given":"Khanh","family":"Dinh","sequence":"additional","affiliation":[{"name":"Irving Institute for Cancer Dynamics, Columbia University , Room 601 Schermerhorn Hall, 1190 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]},{"name":"Department of Statistics, Columbia University , 1255 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S","family":"Roche","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Chu","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-8183","authenticated-orcid":false,"given":"Nicolas","family":"Robine","sequence":"additional","affiliation":[{"name":"New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Early Cancer Institute, University of Cambridge, Clifford Allbutt Building, Adrian Way, Cambridge Biomedical Campus , Cambridge CB2 0AH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhe","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Early Cancer Institute, University of Cambridge, Clifford Allbutt Building, Adrian Way, Cambridge Biomedical Campus , Cambridge CB2 0AH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tavar\u00e9","sequence":"additional","affiliation":[{"name":"Irving Institute for Cancer Dynamics, Columbia University , Room 601 Schermerhorn Hall, 1190 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]},{"name":"Department of Biological Sciences, Columbia University, Room 600 Sherman Fairchild Center , 1212 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]},{"name":"Department of Statistics, Columbia University , 1255 Amsterdam Ave, New York, NY 10027 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-8620","authenticated-orcid":false,"given":"Karol","family":"Nowicki-Osuch","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Tumorigenesis and Molecular Cancer Prevention Group , Im Neuenheimer Feld 280, Heidelberg 69120 ,","place":["Germany"]},{"name":"DKFZ Hector Cancer Institute at the University Medical Center Mannheim , Im Neuenheimer Feld 280, Heidelberg, 69120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"2026100902313306100_B1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"2026100902313306100_B2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41568-018-0084-6","article-title":"Cytokinesis defects and cancer","volume":"19","author":"Lens","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"2026100902313306100_B3","doi-asserted-by":"publisher","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":"2026100902313306100_B4","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41586-020-03133-3","article-title":"Whole-genome doubling confers unique genetic vulnerabilities on tumour cells","volume":"590","author":"Quinton","year":"2021","journal-title":"Nature"},{"key":"2026100902313306100_B5","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/nrc3352","article-title":"Chromothripsis and cancer: causes and consequences of chromosome shattering","volume":"12","author":"Forment","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"2026100902313306100_B6","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1016\/j.devcel.2021.07.009","article-title":"Chromosomal instability accelerates the evolution of resistance to anti-cancer therapies","volume":"56","author":"Lukow","year":"2021","journal-title":"Dev Cell"},{"key":"2026100902313306100_B7","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1038\/s41467-024-46414-5","article-title":"Evolving copy number gains promote tumor expansion and bolster mutational diversification","volume":"15","author":"Wang","year":"2024","journal-title":"Nat Commun"},{"key":"2026100902313306100_B8","doi-asserted-by":"publisher","first-page":"e108389","DOI":"10.15252\/embj.2021108389","article-title":"Cancer evolution: Darwin and beyond","volume":"40","author":"Vendramin","year":"2021","journal-title":"EMBO J"},{"key":"2026100902313306100_B9","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41586-025-09240-3","article-title":"Ongoing genome doubling shapes evolvability and immunity in ovarian cancer","volume":"644","author":"McPherson","year":"2025","journal-title":"Nature"},{"key":"2026100902313306100_B10","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/path.5901","article-title":"Unravelling the tumour genome: the evolutionary and clinical impacts of structural variants in tumourigenesis","volume":"257","author":"Hamdan","year":"2022","journal-title":"J Pathol"},{"key":"2026100902313306100_B11","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1038\/s41467-025-56670-8","article-title":"Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity","volume":"16","author":"Dehkordi","year":"2025","journal-title":"Nat Commun"},{"key":"2026100902313306100_B12","doi-asserted-by":"publisher","first-page":"3090","DOI":"10.1016\/j.molcel.2025.07.007","article-title":"Extrachromosomal DNA biogenesis is dependent on DNA looping and religation by YY1-Lig3-PARylation complex","volume":"85","author":"Qin","year":"2025","journal-title":"Mol Cell"},{"key":"2026100902313306100_B13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1158\/2159-8290.CD-23-1117","article-title":"Disparate pathways for extrachromosomal DNA biogenesis and genomic DNA repair","volume":"15","author":"Rose","year":"2025","journal-title":"Cancer Disc"},{"key":"2026100902313306100_B14","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/s41576-025-00832-3","article-title":"Advances in single-cell DNA sequencing enable insights into human somatic mosaicism","volume":"26","author":"Shao","year":"2025","journal-title":"Nat Rev Genet"},{"key":"2026100902313306100_B15","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/0888-7543(92)90147-K","article-title":"Degenerate oligonucleotide-primed PCR: General amplification of target DNA by a single degenerate primer","volume":"13","author":"Telenius","year":"1992","journal-title":"Genomics"},{"key":"2026100902313306100_B16","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.1073\/pnas.89.13.5847","article-title":"Whole genome amplification from a single cell: implications for genetic analysis","volume":"89","author":"Zhang","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100902313306100_B17","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1101\/gr.180501","article-title":"Rapid amplification of plasmid and phage DNA using Phi29 DNA polymerase and multiply-primed rolling circle amplification","volume":"11","author":"Dean","year":"2001","journal-title":"Genome Res"},{"key":"2026100902313306100_B18","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1517\/14622416.3.4.557","article-title":"Rubicon Genomics, Inc","volume":"3","author":"Langmore","year":"2002","journal-title":"Pharmacogenomics"},{"key":"2026100902313306100_B19","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1126\/science.1229164","article-title":"Genome-wide detection of single-nucleotide and copy-number variations of a single human cell","volume":"338","author":"Zong","year":"2012","journal-title":"Science"},{"key":"2026100902313306100_B20","doi-asserted-by":"publisher","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":"2026100902313306100_B21","doi-asserted-by":"publisher","first-page":"i139","DOI":"10.1093\/bioinformatics\/btn272","article-title":"A fast and flexible method for the segmentation of aCGH data","volume":"24","author":"Ben-Yaacov","year":"2008","journal-title":"Bioinformatics"},{"key":"2026100902313306100_B22","doi-asserted-by":"publisher","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","article-title":"CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing","volume":"12","author":"Talevich","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"2026100902313306100_B23","doi-asserted-by":"publisher","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":"2026100902313306100_B24","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1186\/1471-2105-14-S2-S2","article-title":"CoNVEX: copy number variation estimation in exome sequencing data using HMM","volume":"14","author":"Amarasinghe","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2026100902313306100_B25","doi-asserted-by":"publisher","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":"2026100902313306100_B26","doi-asserted-by":"publisher","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":"2026100902313306100_B27","doi-asserted-by":"publisher","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":"2026100902313306100_B28","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1038\/s41587-021-00911-w","article-title":"Integrative single-cell analysis of allele-specific copy number alterations and chromatin accessibility in cancer","volume":"39","author":"Wu","year":"2021","journal-title":"Nat Biotechnol"},{"key":"2026100902313306100_B29","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s13059-024-03204-y","article-title":"scAbsolute: measuring single-cell ploidy and replication status","volume":"25","author":"Schneider","year":"2024","journal-title":"Genome Biol"},{"key":"2026100902313306100_B30","doi-asserted-by":"publisher","first-page":"gkaf919","DOI":"10.1093\/nar\/gkaf919","article-title":"Absolute copy number aware CNV calling of sub-megabase segments in ultra-low coverage single-cell DNA sequencing data","volume":"53","author":"Kolbeinsdottir","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2026100902313306100_B31","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1198\/016214507000000860","article-title":"Unbalanced Haar technique for nonparametric function estimation","volume":"102","author":"Fryzlewicz","year":"2007","journal-title":"J Am Stat Assoc"},{"key":"2026100902313306100_B32","doi-asserted-by":"publisher","first-page":"e1012902","DOI":"10.1371\/journal.pcbi.1012902","article-title":"CINner: modeling and simulation of chromosomal instability in cancer at single-cell resolution","volume":"21","author":"Dinh","year":"2025","journal-title":"PLoS Comput Biol"},{"key":"2026100902313306100_B33","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1101\/gr.175141.114","article-title":"DNA copy number analysis of fresh and formalin-fixed specimens by shallow whole-genome sequencing with identification and exclusion of problematic regions in the genome assembly","volume":"24","author":"Scheinin","year":"2014","journal-title":"Genome Res"},{"key":"2026100902313306100_B34","doi-asserted-by":"publisher","first-page":"9354","DOI":"10.1038\/s41598-019-45839-z","article-title":"The ENCODE blacklist: identification of problematic regions of the genome","volume":"9","author":"Amemiya","year":"2019","journal-title":"Sci Rep"},{"key":"2026100902313306100_B35","doi-asserted-by":"publisher","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":"2026100902313306100_B36","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.molcel.2020.09.025","article-title":"A highly scalable method for joint whole-genome sequencing and gene-expression profiling of single cells","volume":"80","author":"Zachariadis","year":"2020","journal-title":"Mol Cell"},{"key":"2026100902313306100_B37","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aak9787","article-title":"Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI)","volume":"356","author":"Chen","year":"2017","journal-title":"Science"},{"key":"2026100902313306100_B38","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s13059-021-02406-y","article-title":"SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform","volume":"22","author":"Fan","year":"2021","journal-title":"Genome Biol"},{"key":"2026100902313306100_B39","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1038\/s41467-018-05190-9","article-title":"Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics","volume":"9","author":"Li","year":"2018","journal-title":"Nat Commun"},{"key":"2026100902313306100_B40","doi-asserted-by":"publisher","first-page":"4074","DOI":"10.1038\/s41467-024-47619-4","article-title":"Disentangling oncogenic amplicons in esophageal adenocarcinoma","volume":"15","author":"Ng","year":"2024","journal-title":"Nat Commun"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/18\/gkag960\/71753704\/gkag960.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/18\/gkag960\/71753704\/gkag960.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:31:37Z","timestamp":1791527497000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkag960\/8892726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":40,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9,22]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkag960","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10,14]]},"published":{"date-parts":[[2026,9,22]]},"article-number":"gkag960"}}