ACE: a probabilistic model for characterizing gene-level essentiality in CRISPR screens

Hutton, Elizabeth R, Vakoc, Christopher R, Siepel, Adam (September 2021) ACE: a probabilistic model for characterizing gene-level essentiality in CRISPR screens. Genome Biology, 22 (1). p. 278. ISSN 1474-760X

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Abstract

High-throughput CRISPR-Cas9 knockout screens are widely used to evaluate gene essentiality in cancer research. Here we introduce a probabilistic modeling framework, Analysis of CRISPR-based Essentiality (ACE), that accounts for multiple sources of variation in CRISPR-Cas9 screens and enables new statistical tests for essentiality. We show using simulations that ACE is effective at predicting both absolute and differential essentiality. When applied to publicly available data, ACE identifies known and novel candidates for genotype-specific essentiality, including RNA m6-A methyltransferases that exhibit enhanced essentiality in the presence of inactivating TP53 mutations. ACE provides a robust framework for identifying genes responsive to subtype-specific therapeutic targeting.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > computers bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment bioinformatics > computational biology bioinformatics > genomics and proteomics > computers > computer software Investigative techniques and equipment > CRISPR-Cas9 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:	Hutton, Elizabeth Vakoc, Christopher R. Siepel, Adam
Communities:	CSHL labs > Siepel lab CSHL labs > Vakoc lab School of Biological Sciences > Publications CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	23 September 2021
Date Deposited:	30 Sep 2021 15:56
Last Modified:	13 Feb 2024 17:02
PMCID:	PMC8459512
URI:	https://repository.cshl.edu/id/eprint/40373

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