Multiple-gene targeting and mismatch tolerance can confound analysis of genome-wide pooled CRISPR screens.

ABSTRACT:

Background

Genome-wide loss-of-function screens using the CRISPR/Cas9 system allow the efficient discovery of cancer cell vulnerabilities. While several studies have focused on correcting for DNA cleavage toxicity biases associated with copy number alterations, the effects of sgRNAs co-targeting multiple genomic loci in CRISPR screens have not been discussed.

Results

In this work, we analyze CRISPR essentiality screen data from 391 cancer cell lines to characterize biases induced by multi-target sgRNAs. We investigate two types of multi-targets: on-targets predicted through perfect sequence complementarity and off-targets predicted through sequence complementarity with up to two nucleotide mismatches. We find that the number of on-targets and off-targets both increase sgRNA

SUBMITTER: Fortin JP 

PROVIDER: S-EPMC6346559 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature