Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression [article]

Noemi Andor, Billy T Lau, Claudia Catalanotti, Vijay Kumar, Anuja Sathe, Kamila Belhocine, Tobias D Wheeler, Andrew D Price, Maengseok Song, David Stafford, Zachary Bent, Laura DeMare (+21 others)
2018 bioRxiv   pre-print
Sequencing the genomes of individual cancer cells provides the highest resolution picture of intratumoral heterogeneity. To enable high throughput single cell DNAseq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNAseq analysis on these same cancers and used
more » ... number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection where the percentage of replicating cells per clone is higher than expected indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.
doi:10.1101/445932 fatcat:rfk67xvlmrfi7epcxhfhdmfxym