TY - JOUR T1 - Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression JF - bioRxiv DO - 10.1101/445932 SP - 445932 AU - Noemi Andor AU - Billy T. Lau AU - Claudia Catalanotti AU - Vijay Kumar AU - Anuja Sathe AU - Kamila Belhocine AU - Tobias D. Wheeler AU - Andrew D. Price AU - Maengseok Song AU - David Stafford AU - Zachary Bent AU - Laura DeMare AU - Lance Hepler AU - Susana Jett AU - Bill Kengli Lin AU - Shamoni Maheshwari AU - Anthony J. Makarewicz AU - Mohammad Rahimi AU - Sanjam S. Sawhney AU - Martin Sauzade AU - Joe Shuga AU - Katrina Sullivan-Bibee AU - Adam Weinstein AU - Wei Yang AU - Yifeng Yin AU - Matthew A. Kubit AU - Jiamin Chen AU - Susan M. Grimes AU - Carlos Jose Suarez AU - George A. Poultsides AU - Michael Schnall-Levin AU - Rajiv Bharadwaj AU - Hanlee P. Ji Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/10/17/445932.1.abstract N2 - 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. ER -