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bioRxiv · 10.1101/2022.05.10.491431

Identification of cancer drivers from tumor-only RNA-seq with RNA-VACAY

Akutagawa, J.·Mak, A. J.·Aspden, J.·Brooks, A. N.
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Abstract

Detecting somatic mutations is a cornerstone of cancer genomics and clinical genotyping; however, there has been little systematic evaluation of the utility of RNA sequencing (RNA-seq) for somatic variant detection and driver mutation analysis. Variants found in RNA-Seq are also expressed, reducing the identification of passenger mutations and would not suffer from annotation bias observed in whole-exome sequencing (WES). We developed RNA-VACAY, a containerized pipeline that automates somatic variant calling from tumor RNA-seq data, alone, and evaluated its performance on simulated data and 1,349 RNA-seq samples with matched whole-genome sequencing (WGS). RNA-VACAY was able to detect at least 1 putative driver gene in 15 out of 16 cancer types and identified known driver mutations in 5 and 3 UTRs. The computational cost and time to generate and analyze RNA-seq data is lower than WGS or WES, which decreases the resources necessary for somatic variant detection. This study demonstrates the utility of RNA-seq to detect cancer drivers.

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Akutagawa, J., Mak, A. J., Aspden, J., Brooks, A. N.. 2022-05-11. Identification of cancer drivers from tumor-only RNA-seq with RNA-VACAY. https://doi.org/10.1101/2022.05.10.491431

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