CoRe: A robustly benchmarked R package for the identification of core fitness genes in genome-wide pooled CRISPR knock-out screens

Abstract

CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. Identifying from these screens the genes that are essential for cell survival invariantly across tissues, conditions, and genomic-contexts (core-fitness genes), is of paramount importance to assess the safety profile of candidate therapeutic targets and for elucidating mechanisms involved in tissue-specific genetic diseases. We present CoRe: An R package implementing novel methods for identifying core-fitness genes from joint analyses of multiple CRISPR-Cas9 screens. We demonstrate that CoRe outperforms state-of-the-art tools, yielding more reliable sets of core-fitness genes than existing and widely used reference sets.