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Copy-scAT: An R package for detection of large-scale and focal copy number alterations in single-cell chromatin accessibility datasets

Ana Nikolic, Divya Singhal, Katrina Ellestad, Michael Johnston, Aaron Gillmor, Sorana Morrissy, Jennifer A Chan, Paola Neri, Nizar Bahlis, View ORCID ProfileMarco Gallo
doi: https://doi.org/10.1101/2020.09.21.305516
Ana Nikolic
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Divya Singhal
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Katrina Ellestad
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Michael Johnston
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Aaron Gillmor
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Sorana Morrissy
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Jennifer A Chan
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
4Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Paola Neri
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
4Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Nizar Bahlis
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
4Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Marco Gallo
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
3Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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  • ORCID record for Marco Gallo
  • For correspondence: marco.gallo@ucalgary.ca
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ABSTRACT

The single-cell assay for transposase accessible chromatin (scATAC) is an invaluable asset to profile the epigenomic landscape of heterogeneous cells populations in complex tissue and organ systems. However, the lack of tools that enable the use of scATAC data to discriminate between malignant and non-malignant cells has prevented the widespread application of this technique to clinical tumor samples. Here we describe Copy-scAT, a new computational tool that uses scATAC data to infer both large-scale and focal copy number alterations. Copy-scAT can call both clonal and subclonal copy number changes, allowing identification of cancer cells and cell populations that putatively constitute the tumor microenvironment. Copy-scAT therefore enables downstream chromatin accessibility studies that focus on malignant or non-malignant cell populations in clinical samples that are profiled by scATAC.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 22, 2020.
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Copy-scAT: An R package for detection of large-scale and focal copy number alterations in single-cell chromatin accessibility datasets
Ana Nikolic, Divya Singhal, Katrina Ellestad, Michael Johnston, Aaron Gillmor, Sorana Morrissy, Jennifer A Chan, Paola Neri, Nizar Bahlis, Marco Gallo
bioRxiv 2020.09.21.305516; doi: https://doi.org/10.1101/2020.09.21.305516
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Copy-scAT: An R package for detection of large-scale and focal copy number alterations in single-cell chromatin accessibility datasets
Ana Nikolic, Divya Singhal, Katrina Ellestad, Michael Johnston, Aaron Gillmor, Sorana Morrissy, Jennifer A Chan, Paola Neri, Nizar Bahlis, Marco Gallo
bioRxiv 2020.09.21.305516; doi: https://doi.org/10.1101/2020.09.21.305516

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