TY - JOUR A1 - Allen, Felicity A1 - Behan, Fiona A1 - Khodak, Anton A1 - Iorio, Francesco A1 - Yusa, Kosuke A1 - Garnett, Mathew A1 - Parts, Leopold T1 - JACKS: joint analysis of CRISPR/Cas9 knockout screens Y1 - 2019/03/01 JF - Genome Research JO - Genome Research SP - 464 EP - 471 DO - 10.1101/gr.238923.118 VL - 29 IS - 3 UR - http://genome.cshlp.org/content/29/3/464.abstract N2 - Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. However, their range of applications remains limited by signal variability from different guide RNAs 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. ER -