Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction.

ABSTRACT:

Background

Millions of nucleotide variants are identified through cancer genome sequencing and it is clinically important to identify the pathogenic variants among them. By introducing base substitutions at guide RNA target regions in the genome, CRISPR-Cas9-based base editors provide the possibility for evaluating a large number of variants in their genomic context. However, the variability in editing efficiency and the complexity of outcome mapping are two existing problems for assigning guide RNA effects to variants in base editing screens.

Results

To improve the identification of pathogenic variants, we develop a framework to combine base editing screens with sgRNA efficiency and outcome mapping. We apply the method to evaluate more than 9000 variants across all the exon

SUBMITTER: Huang C 

PROVIDER: S-EPMC7945310 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature