beditor: A computational workflow for designing libraries of guide RNAs for CRISPR base editing

Abstract

CRISPR-mediated base editors have opened unique avenues for scar-free genome-wide mutagenesis. Here, we describe a comprehensive computational workflow called beditor that can be broadly adapted for designing guide RNA libraries with a range of CRISPR-mediated base editors, PAM recognition sequences and genomes of many species. Additionally, in order to assist users in selecting the best sets of guide RNAs for their experiments, a priori estimates, called beditor scores are calculated. These beditor scores are intended to select guide RNAs that conform to requirements for optimal base editing: editable base falls within maximum activity window of the CRISPR-mediated base editor and produces non-confounding mutational effects with minimal off-target effects. We demonstrate the utility of the software by designing guide RNAs for base-editing mediated edition of thousands of clinically important human disease mutations.