Study

Scalable whole-genome single-cell library preparation without pre-amplification

Study ID Alternative Stable ID Type
EGAS00001002170 Other

Study Description

Single-cell genomics is critical for understanding cellular heterogeneity in cancer, but existing library preparation methods are expensive, require sample preamplification and introduce coverage bias. Here we describe direct library preparation (DLP), a robust, scalable, and high-fidelity method that uses nanoliter-volume transposition reactions for single-cell whole-genome library preparation without preamplification. We examined 782 cells from cell lines and triple-negative breast xenograft tumors. Low-depth sequencing, compared with existing methods, revealed greater coverage uniformity and more reliable detection of copy-number alterations. Using phylogenetic analysis, we found minor xenograft subpopulations that were undetectable by bulk sequencing, as well as dynamic clonal expansion and diversification between passages. Merging single-cell genomes in silico, we generated "bulk-equivalent" genomes with high depth and uniform coverage. Thus, low-depth sequencing of DLP libraries may provide an attractive replacement for conventional bulk sequencing methods, permitting analysis ... (Show More)

Study Datasets 5 datasets.

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Dataset ID Description Technology Samples
EGAD00001003148
Microfluidic direct library preparation (DLP) single-cell whole-genome BAM files for near-diploid immortalized lymphoblastoid cell line GM18507.
NextSeq 500 192
EGAD00001003149
Microfluidic direct library preparation (DLP) single-cell whole-genome BAM files for third-passage patient-derived primary triple-negative breast cancer xenograft SA501X3F.
Illumina HiSeq 2500 384
EGAD00001003150
Microfluidic direct library preparation (DLP) single-cell whole-genome BAM files for fourth-passage patient-derived primary triple-negative breast cancer xenograft SA501X4F.
Illumina HiSeq 2500 384
EGAD00001003151
Bulk whole-genome BAM files for 184-hTERT-L2, SA501X3F, and SA501X4F.
Illumina HiSeq 2500 3
EGAD00001003152
Microfluidic direct library preparation (DLP) single-cell whole-genome BAM files for near-diploid immortalized breast epithelial cell line 184-hTERT-L2.
Illumina HiSeq 2500 192

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