Journal
CELL
Volume 179, Issue 5, Pages 1207-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.10.026
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Funding
- 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
- Cycle for Survival benefiting Memorial Sloan-Kettering Cancer Center
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Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.
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