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Nikolic A, Singhal D, Ellestad K, et al. Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer. Sci Adv. 2021;7(42):eabg6045doi: 10.1126/sciadv.abg6045.
Nikolic, A., Singhal, D., Ellestad, K., Johnston, M., Shen, Y., Gillmor, A., Morrissy, S., Cairncross, J. G., Jones, S., Lupien, M., Chan, J. A., Neri, P., Bahlis, N., & Gallo, M. (2021). Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer. Science advances, 7(42), eabg6045. https://doi.org/10.1126/sciadv.abg6045
Nikolic, Ana, et al. "Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer." Science advances vol. 7,42 (2021): eabg6045. doi: https://doi.org/10.1126/sciadv.abg6045
Nikolic A, Singhal D, Ellestad K, Johnston M, Shen Y, Gillmor A, Morrissy S, Cairncross JG, Jones S, Lupien M, Chan JA, Neri P, Bahlis N, Gallo M. Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer. Sci Adv. 2021 Oct 15;7(42):eabg6045. doi: 10.1126/sciadv.abg6045. Epub 2021 Oct 13. PMID: 34644115; PMCID: PMC8514091.
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Sci Adv. 2021 Oct 15;7(42):eabg6045. doi: 10.1126/sciadv.abg6045. Epub 2021 Oct 13.

Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer.

Science advances

Ana Nikolic, Divya Singhal, Katrina Ellestad, Michael Johnston, Yaoqing Shen, Aaron Gillmor, Sorana Morrissy, J Gregory Cairncross, Steven Jones, Mathieu Lupien, Jennifer A Chan, Paola Neri, Nizar Bahlis, Marco Gallo

Affiliations

  1. Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  2. Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  3. Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  4. Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
  5. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
  6. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  7. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  8. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  9. Ontario Institute for Cancer Research, Toronto, ON, Canada.

PMID: 34644115 PMCID: PMC8514091 DOI: 10.1126/sciadv.abg6045

Abstract

Single-cell epigenomic assays have tremendous potential to illuminate mechanisms of transcriptional control in functionally diverse cancer cell populations. However, application of these techniques to clinical tumor specimens has been hampered by the current inability to distinguish malignant from nonmalignant cells, which potently confounds data analysis and interpretation. Here, we describe Copy-scAT, an R package that uses single-cell epigenomic data to infer copy number variants (CNVs) that define cancer cells. Copy-scAT enables studies of subclonal chromatin dynamics in complex tumors like glioblastoma. By deploying Copy-scAT, we uncovered potent influences of genetics on chromatin accessibility profiles in individual subclones. Consequently, some genetic subclones were predisposed to acquire stem-like or more differentiated molecular phenotypes, reminiscent of developmental paradigms. Copy-scAT is ideal for studies of the relationships between genetics and epigenetics in malignancies with high levels of intratumoral heterogeneity and to investigate how cancer cells interface with their microenvironment.

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