MAUDE: inferring expression changes in sorting-based CRISPR screens

Improved methods are needed to model CRISPR screen data for interrogation of genetic elements that alter reporter gene expression readout. We create 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 demonstrate that MAUDE outperforms previous approaches and provide experimental design guidelines to best leverage MAUDE, which is available on https://github.com/Carldeboer/MAUDE.