RT Journal Article SR Electronic T1 MAUDE: Inferring expression changes in sorting-based CRISPR screens JF bioRxiv FD Cold Spring Harbor Laboratory SP 819649 DO 10.1101/819649 A1 de Boer, Carl G. A1 Ray, John P. A1 Hacohen, Nir A1 Regev, Aviv YR 2019 UL http://biorxiv.org/content/early/2019/10/28/819649.abstract AB Pooled CRISPR screens allow high-throughput interrogation of genetic elements that alter expression of a reporter gene readout. New computational methods are needed to model these data. We created MAUDE (Mean Alterations Using Discrete Expression) for quantifying the impact of guide RNAs on a target gene’s expression in a pooled, sorting-based expression screen. MAUDE quantifies guide-level effects by modeling the distribution of cells across sorting expression bins. It then combines guides to estimate the statistical significance and effect size of targeted genetic elements. We show that MAUDE significantly improves over previous approaches and provide experimental design guidelines to best leverage MAUDE.AUROCArea under the receiver operating characteristic curveCaRECRISPRa responsive element (as identified in 9)CRISPRclustered regularly interspaced short palindromic repeatsFDRfalse discovery rateMAUDEmean alterations using discrete expressionSDstandard deviationTSStranscription start site