Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification.

ABSTRACT: CRISPR base editing screens are powerful tools for studying disease-associated variants at scale. However, the efficiency and precision of base editing perturbations vary, confounding the assessment of variant-induced phenotypic effects. Here, we provide an integrated pipeline that improves the estimation of variant impact in base editing screens. We perform high-throughput ABE8e-SpRY base editing screens with an integrated reporter construct to measure the editing efficiency and outcomes of each gRNA alongside their phenotypic consequences. We introduce BEAN, a Bayesian network that accounts for per-guide editing outcomes and target site chromatin accessibility to estimate variant impacts. We show this pipeline attains superior performance compared to existing tools in variant classificat

SUBMITTER: Ryu J 

PROVIDER: S-EPMC10508837 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature