ArticleCell2019
Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.
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Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
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162citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
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Who cites it
162 citing papers in PubMed, 299 citations in OpenAlex.
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- LeafRank: A phylodynamic framework for inferring relative fitness from single-cell phylogenies in chromosomally unstable tumors.bioRxiv : the preprint server for biology · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
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- Chromosomal instability and genomic alterations in cholangiocarcinoma from Northeastern Thailand.The Journal of pathology · 2025Article
- Article
102 more citing papers are in PubMed but not listed here.
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Authors and funding
51 authors at 4 institutions in 2 countries.
Emma LaksDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, Canada.
Andrew McPhersonDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA.
Hans ZahnDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, Canada; Centre for High Throughput Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Daniel LaiDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Adi SteifDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, Canada.
Jazmine BrimhallDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Justina BieleDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Beixi WangDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Tehmina MasudDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Jerome TingDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Diljot GrewalDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA.
Cydney NielsenDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Samantha LeungDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA.
Viktoria BojilovaDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA.
Maia SmithDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Oleg GolovkoDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Steven PoonDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada.
Peter EirewDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Farhia KabeerDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Teresa Ruiz de AlgaraDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
So Ra LeeDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
M Jafar TaghiyarDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Curtis HuebnerDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Jessica NgoDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Tim ChanDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Spencer Vatrt-WattsDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA.
Pascale WaltersDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Nafis AbrarDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Sophia ChanDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Matt WiensDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Lauren MartinDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
R Wilder ScottDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
T Michael UnderhillCentre for High Throughput Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Elizabeth ChavezCentre for Lymphoid Cancer, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada.
Christian SteidlCentre for Lymphoid Cancer, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada.
Daniel Da CostaDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Centre for High Throughput Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Yussanne MaMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Robin J N CoopeMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Richard CorbettMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Stephen PleasanceMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Richard MooreMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Andrew J MungallMichael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Colin MarDepartment of Radiology, BC Cancer, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
Fergus CaffertyDepartment of Radiology, BC Cancer, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
Karen GelmonDepartment of Medical Oncology, BC Cancer, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
Stephen ChiaDepartment of Medical Oncology, BC Cancer, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
CRUK IMAXT Grand Challenge Team
Marco A MarraDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Carl HansenCentre for High Throughput Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Sohrab P ShahDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 417 East 68th St., New York, NY 10065, USA. Electronic address: shahs3@mskcc.org.
Samuel AparicioDepartment of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada. Electronic address: saparicio@bccrc.ca.
BC Cancer Agency · CAUniversity of British Columbia · CACanada's Michael Smith Genome Sciences Centre · CAMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MCancer Research UK 21143NCI NIH HHS P30 CA008748
Abstract
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.
Indexed as
Genome, HumanHigh-Throughput Nucleotide SequencingSingle-Cell AnalysisAneuploidyAnimalsCell CycleCell Line, TumorCell ShapeCell SurvivalChromosomes, HumanClone CellsDiploidyDNA ReplicationDNA Transposable ElementsFemaleGenotypeDNA Transposable Elementsaneuploidycancer genomicscell cyclecopy numberDNA sequencinggenomic instabilitysingle celltumor evolutiontumor heterogeneity
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