biostudies-literatureLaks ETerry Fox Research InstituteCancer Research UKNCI NIH HHSCanadian Institutes of Health ResearchCanadian Cancer Society Research Institute1207-1221.e22https://www.ebi.ac.uk/biostudies/studies/S-EPMC6912164biostudies-literatureUnknown179(5)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 ploCellClonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.PMC6912164S_4073S_340924042P30 CA00874821143S_3417Grewal DGelmon KGreenwood WShah SPDuran LSShah SBiele JWilliams EAlon SWalters PUnderhill TMCannell IMartin LWalton NANgo JGonzalez-Fernandez CChan TChan SWassie ATBruna AEirew PBattistoni GPoon SCRUK IMAXT Grand Challenge TeamNielsen CBurger MZheng PFisher EShea AVogl SQosaj FCasbolt HTietscher SLee MCorbett RHannon GJScott RWLee HSolares EGSteif AMarra MAFan JChornay NKabeer FBalasubramanian SVatrt-Watts SMcPherson ABodenmiller BLubling YZahn HCaldas CChia SBojilova VCui YO'Flanagan CBrimhall JLee SRSawicka KDa Costa DSinha AWang BWatson SGolovko ORuiz TJoyce JAMar CAparicio SDinh KGoodwin DMasud TCoope RJNTavare SXia CLaks ETaghiyar MJMungall AJGrimaldi FCafferty FKuett LNugent FLi YSteidl CJauset CChavez EEmenari AHuebner CLai DMulvey CRibes MPWiens MMillar NMa YPleasance SBoyden EVazquez-Garcia IBecker RDariush AAbrar NKovacevic TYoldas AKMarti ABressan DKunes RAl Sa'd MHansen CRuiz de Algara THarris OSmith AHarris SZhuang XMoore RTing JRueda OPearsall IWild SSmith MCallari MLerda GHausser JKaragiannis EWindager JLeung SfalseClonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.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 plo2019-01-01T00:00:00Z2019 Nov2026-05-01T10:15:32.795Z2025-05-29T22:05:37.688ZS-EPMC69121643173085810.1016/j.cell.2019.10.026