RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2019 
FD March 01 
VO 29 
IS 3 
SP 464 
OP 471 
DO 10.1101/gr.238923.118 
UL http://genome.cshlp.org/content/29/3/464.abstract 
AB 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.