MAUDE: inferring expression changes in sorting-based CRISPR screens

Carl G de Boer; John P Ray; Nir Hacohen; Aviv Regev

doi:10.1186/s13059-020-02046-8

MAUDE: inferring expression changes in sorting-based CRISPR screens

Genome Biol. 2020 Jun 3;21(1):134. doi: 10.1186/s13059-020-02046-8.

Authors

Carl G de Boer^{1

2}, John P Ray³, Nir Hacohen^{4

3

5}, Aviv Regev^{6

7}

Affiliations

¹ Klarman Cell Observatory, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA. carl.deboer@ubc.ca.
² School of Biomedical Engineering, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. carl.deboer@ubc.ca.
³ Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA.
⁴ Klarman Cell Observatory, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA.
⁵ Center for Cancer Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁶ Klarman Cell Observatory, Broad Institute of MIT and Harvard University, Cambridge, MA, 02142, USA. aregev@broadinstitute.org.
⁷ Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA. aregev@broadinstitute.org.

Abstract

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.

Keywords: CRISPR/Cas9; Enhancers; Gene expression; Gene regulation; Pooled screen; R; Transcriptional regulation.

Publication types

Evaluation Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
CRISPR-Cas Systems
Clustered Regularly Interspaced Short Palindromic Repeats*
Gene Expression*
Genetic Techniques*
Models, Genetic
RNA, Guide, CRISPR-Cas Systems*
Software*

Substances

RNA, Guide, CRISPR-Cas Systems

Abstract

Publication types

MeSH terms

Substances

Grants and funding