RT Journal A1 Allen, Felicity A1 Khodak, Anton A1 Behan, Fiona A1 Iorio, Francesco A1 Yusa, Kosuke A1 Garnett, Mathew A1 Parts, Leopold T1 JACKS: joint analysis of CRISPR/Cas9 knockout screens JF Genome Research JO Genome Research YR 2019 FD January 23 DO 10.1101/gr.238923.118 SP gr.238923.118 UL http://genome.cshlp.org/content/early/2019/01/23/gr.238923.118.abstract AB 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.