RT Journal Article SR Electronic T1 Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 445932 DO 10.1101/445932 A1 Noemi Andor A1 Billy T. Lau A1 Claudia Catalanotti A1 Vijay Kumar A1 Anuja Sathe A1 Kamila Belhocine A1 Tobias D. Wheeler A1 Andrew D. Price A1 Maengseok Song A1 David Stafford A1 Zachary Bent A1 Laura DeMare A1 Lance Hepler A1 Susana Jett A1 Bill Kengli Lin A1 Shamoni Maheshwari A1 Anthony J. Makarewicz A1 Mohammad Rahimi A1 Sanjam S. Sawhney A1 Martin Sauzade A1 Joe Shuga A1 Katrina Sullivan-Bibee A1 Adam Weinstein A1 Wei Yang A1 Yifeng Yin A1 Matthew A. Kubit A1 Jiamin Chen A1 Susan M. Grimes A1 Carlos Jose Suarez A1 George A. Poultsides A1 Michael Schnall-Levin A1 Rajiv Bharadwaj A1 Hanlee P. Ji YR 2018 UL http://biorxiv.org/content/early/2018/10/17/445932.1.abstract AB Sequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq 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 RNA-Seq analysis on these same cancers and used copy 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.