JACKS: joint analysis of CRISPR/Cas9 knockout screens
Abstract
CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. Their range of applications remains limited by signal variability from different guideRNAs that target the same gene, which confounds gene effect estimation, and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyzes screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification over processing a single screen at a time, and outperforms existing methods. This more efficient analysis gives additional hits, and allows designing libraries with a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.
- Received April 27, 2018.
- Accepted January 16, 2019.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.
