Wavelet-based whole genome doubling aware single-cell copy number calling
7 affiliations
- 1Irving Institute for Cancer Dynamics, Columbia University , Room 601 Schermerhorn Hall, 1190 Amsterdam Ave, New York, NY 10027 ,
- 2Department of Biological Sciences, Columbia University, Room 600 Sherman Fairchild Center , 1212 Amsterdam Ave, New York, NY 10027 ,
- 3New York Genome Center , 101 Avenue of the Americas, New York, NY 10013 ,
- 4Department of Statistics, Columbia University , 1255 Amsterdam Ave, New York, NY 10027 ,
- 5Early Cancer Institute, University of Cambridge, Clifford Allbutt Building, Adrian Way, Cambridge Biomedical Campus , Cambridge CB2 0AH ,
- 6German Cancer Research Center (DKFZ) Heidelberg, Tumorigenesis and Molecular Cancer Prevention Group , Im Neuenheimer Feld 280, Heidelberg 69120 ,
- 7DKFZ Hector Cancer Institute at the University Medical Center Mannheim , Im Neuenheimer Feld 280, Heidelberg, 69120 ,
Abstract
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’s genome and ligating sequencing adapters using a modified Tn5 transposase, and sequencing to <0.1× 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.
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BibTeX
@article{wesley2026waveletbased,
title = {{Wavelet-based whole genome doubling aware single-cell copy number calling}},
author = {Benjamin K Wesley and Frank Wos and Soren Germer and Jade E B Carter and Silas Maniatis and Khanh Dinh and James S Roche and Timothy R Chu and Nicolas Robine and Rebecca C Fitzgerald and Lizhe Zhuang and Simon Tavaré and Karol Nowicki-Osuch},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag960},
url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag960/8892726},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Wavelet-based whole genome doubling aware single-cell copy number calling
AU - Benjamin K Wesley
AU - Frank Wos
AU - Soren Germer
AU - Jade E B Carter
AU - Silas Maniatis
AU - Khanh Dinh
AU - James S Roche
AU - Timothy R Chu
AU - Nicolas Robine
AU - Rebecca C Fitzgerald
AU - Lizhe Zhuang
AU - Simon Tavaré
AU - Karol Nowicki-Osuch
PY - 2026
DA - 2026/10/09
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag960
UR - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag960/8892726
AB - 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’s genome and ligating sequencing adapters using a modified Tn5 transposase, and sequencing to <0.1× 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.
SN - 0305-1048
SN - 1362-4962
ER -