Cancer Cell Line Encyclopedia (CCLE) Long Read RNA-seq

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous backbone upon which to study genetic variants, candidate targets, small molecule and biologic therapeutics and to identify new markers of cancer dependencies. Here we provide a substantial expansion of the CCLE to include long read transcriptome characterization using the state-of-art MAS-ISO-seq technique.In this pilot study, we performed MAS-ISO-seq using the bulk-8mer method, and then sequenced the libraries on the Revio for the 9 CCLE cell lines. For the same cell lines, we also sequenced the paired-end short reads using the Illumina TruSeq on a Novaseq 6000 machine. Here we developed a new computational tool CTAT-LR-fusion to detect fusion transcripts from long read RNA-seq with or without companion short reads. We demonstrate that CTAT-LR-fusion exceeds fusion detection accuracy of alternative methods as benchmarked with simulated and real long read RNA-seq of the 9 CCLE cell lines.