JACKS: joint analysis of CRISPR/Cas9 knock-out screens

Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. Their range of applications remains limited by signal variability from different guide RNAs targeting the same gene, which confounds analysis, and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyses screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification, and allows a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.