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Clonal 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 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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001004553 Illumina HiSeq 2500 980
EGAD00001004719 Illumina HiSeq 2500 1340
EGAD00001004720 Illumina HiSeq 2500 2057
EGAD00001004721 Illumina HiSeq 2500 1970
EGAD00001004722 Illumina HiSeq 2500 2091
EGAD00001004723 Illumina HiSeq 2500 1267
EGAD00001004724 Illumina HiSeq 2500 230
EGAD00001004725 Illumina HiSeq 2500 232
EGAD00001004726 Illumina HiSeq 2500 239
EGAD00001004727 Illumina HiSeq 2500 692
EGAD00001004728 Illumina HiSeq 2500 612
EGAD00001004729 Illumina HiSeq 2500 1700
EGAD00001004730 Illumina HiSeq 2500 628
EGAD00001004731 Illumina HiSeq 2500 596
EGAD00001004732 Illumina HiSeq 2500 1735
EGAD00001004733 NextSeq 550 585
EGAD00001004734 NextSeq 550 766
EGAD00001004735 Illumina HiSeq 2500 2055
EGAD00001004736 Illumina HiSeq 2500 620
EGAD00001004737 NextSeq 550 624
EGAD00001004738 NextSeq 550 481
EGAD00001004739 Illumina HiSeq 2500 378
EGAD00001004740 Illumina HiSeq 2500 735
EGAD00001004741 Illumina HiSeq 2500 718
EGAD00001004742 NextSeq 550 493
EGAD00001004743 Illumina HiSeq 2500 1222
EGAD00001004744 Illumina HiSeq 2500 522
EGAD00001004745 Illumina HiSeq 2500 488
EGAD00001004746 NextSeq 550 509
EGAD00001004747 NextSeq 550 604
EGAD00001004748 NextSeq 550 626
EGAD00001004749 Illumina HiSeq 2500 635
EGAD00001004750 HiSeq X Five 1522
EGAD00001004751 NextSeq 550 465
EGAD00001004752 Illumina HiSeq 2500 606
EGAD00001004753 NextSeq 550 615
EGAD00001004754 NextSeq 550 636
EGAD00001004755 HiSeq X Five 968
EGAD00001004756 NextSeq 550 480
EGAD00001004757 NextSeq 550 561
EGAD00001004758 HiSeq X Five 844
EGAD00001004759 HiSeq X Five 928
EGAD00001004760 HiSeq X Five 635
EGAD00001004761 HiSeq X Five 1072
EGAD00001004762 HiSeq X Five 1436
EGAD00001004763 HiSeq X Five 589
EGAD00001004764 HiSeq X Five 656
EGAD00001004765 HiSeq X Five 648
EGAD00001004766 HiSeq X Five 375
EGAD00001004767 HiSeq X Five 755
EGAD00001004768 HiSeq X Five 492
EGAD00001004769 HiSeq X Five 531
EGAD00001004770 HiSeq X Five 1063
EGAD00001004771 HiSeq X Five Illumina HiSeq 2500 742
EGAD00001005338 HiSeq X Five 3
EGAD00001005340 HiSeq X Five 3
EGAD00001005345 HiSeq X Five 4
EGAD00001005347 HiSeq X Five 3
EGAD00001005348 HiSeq X Five 3
EGAD00001005353 HiSeq X Five 3
EGAD00001005354 HiSeq X Five 3
EGAD00001005355 HiSeq X Five 2
EGAD00001007756 Illumina HiSeq 2000 1
Publications Citations
clonealign: statistical integration of independent single-cell RNA and DNA sequencing data from human cancers.
Genome Biol 20: 2019 54
48
Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.
Cell 179: 2019 1207-1221.e22
95
Single-cell genomic variation induced by mutational processes in cancer.
Nature 612: 2022 106-115
27
Computational Methods for Single-cell Multi-omics Integration and Alignment.
Genomics Proteomics Bioinformatics 20: 2022 836-849
12
Reconstructing clonal tree for phylo-phenotypic characterization of cancer using single-cell transcriptomics.
Nat Commun 14: 2023 982
4
Fast intratumor heterogeneity inference from single-cell sequencing data.
Nat Comput Sci 2: 2022 577-583
1
Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes.
Nat Genet 56: 2024 889-899
1