Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing

The CRUK IMAXT Grand Challenge Team

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

A high-throughput method for amplication-free single-cell whole-genome sequencing can be scaled up to analyze tens of thousands of cells from different tissues and clinical sample types and identifies replication states, aneuploidies, and subclonal mutations.

Original languageEnglish
Pages (from-to)1207-1221.e22
JournalCell
Volume179
Issue number5
DOIs
StatePublished - 14 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Funding

The work described and the laboratories of S.A. and S.S. are supported by BC Cancer Foundation, Canadian Institutes of Health Research (CIHR), Canadian Cancer Society Research Institute (CCSRI), Terry Fox Research Institute (TFRI), Canada Foundation for Innovation (CFI), Canada Research Chairs program, Michael Smith Foundation for Health Research (MSFHR), Genome British Columbia, Genome Canada, CANARIE, Cancer Research UK Grand challenge IMAXT award (CRUK), Susan G. Komen, and Cycle for Survival benefiting Memorial Sloan-Kettering Cancer Center. We would like to thank Microsoft Azure for providing cloud computing credits that made this study possible. S.A. S.P.S. and C.H. conceived and organized the research and wrote and reviewed the manuscript. E.L. H.Z. A.S. A.M.P. and D.L. developed and tested methods, performed analysis, and wrote the manuscript. J. Brimhall, J. Biele, and B.W. carried out tissue preparation, DLP+ library construction, and sequencing. T.M. and J.T. developed the 184-hTERT TP53 null line 95.22 and 99.5. C.N. S.L. V.B. M.S. and O.G. developed and deployed Montage and https://www.cellmine.org. P.E. F.K. T.R.d.A. and S.R.L. performed PDX transplants and passaging. S. Poon developed the microscope image analysis SmartChipApp. M.J.T. J.N. S.V.-W. N.A. and M.W. developed Colossus. C.H. T.C. P.W. and S.C. developed Sisyphus. A.M.P. J.N. S.V.-W. N.A. and M.W. developed Tantalus. D.G. C.H. T.C. P.W. and S.C. developed and ran the single-cell analysis pipeline. L.M. R.W.S. and T.M.U. developed the mouse synovial sarcoma model and isolated and supplied the cells. E.C. and C.S. provided follicular lymphoma samples. R.J.N.C. and H.Z. developed custom parts for DLP+. D.D.C. provided LabView assistance. S. Pleasance, Y.M. R.C. R.M. A.J.M. and M.A.M. assisted with sequence generations and single-cell experiments. S.P.S. and S.A. are founders and shareholders of Contextual Genomics Inc. The work described and the laboratories of S.A. and S.S. are supported by BC Cancer Foundation , Canadian Institutes of Health Research (CIHR), Canadian Cancer Society Research Institute (CCSRI), Terry Fox Research Institute (TFRI), Canada Foundation for Innovation (CFI), Canada Research Chairs program, Michael Smith Foundation for Health Research (MSFHR), Genome British Columbia , Genome Canada , CANARIE , Cancer Research UK Grand challenge IMAXT award (CRUK), Susan G. Komen, and Cycle for Survival benefiting Memorial Sloan-Kettering Cancer Center . We would like to thank Microsoft Azure for providing cloud computing credits that made this study possible.

FundersFunder number
A.M.P.
BC Cancer Foundation
Cancer Research UK Grand
Contextual Genomics Inc
E.C.
L.M.
S.C.
T.M.U.
Microsoft
Memorial Sloan-Kettering Cancer Center
E.L. Wiegand Foundation
Canarie
Genome Canada
M.S.I. Foundation
Canadian Cancer Society Research Institute
Canadian Institutes of Health Research
Canada Foundation for Innovation
Genome British Columbia
Michael Smith Foundation for Health Research
Cancer Research UK
Canada Research Chairs
Terry Fox Research Institute

    Keywords

    • DNA sequencing
    • aneuploidy
    • cancer genomics
    • cell cycle
    • copy number
    • genomic instability
    • single cell
    • tumor evolution
    • tumor heterogeneity

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