AsCRISPR: A Web Server for Allele-Specific Single Guide RNA Design in Precision Medicine

Abstract

Allele-specific genomic targeting by CRISPR is a versatile strategy that has been increasingly exploited not only in treating inherited dominant diseases and mutation-driven cancers, but also in other important fields such as genome imprinting, haploinsufficiency, and genome loci imaging. Despite its tremendous utilities, few bioinformatic tools have been implemented for the allele-specific purpose of CRISPR. We thus developed AsCRISPR (Allele-specific CRISPR), a comprehensive web tool to aid the design of short-guide RNA (sgRNA) sequences that can discriminate between alleles. AsCRISPR allows users to analyze both their own identified variants and heterozygous single nucleotide polymorphisms and, importantly, output the candidate sgRNAs and their quality control information. To facilitate targeting dominant diseases, AsCRISPR analyzed dominant single nucleotide variants (SNVs) retrieved from ClinVar and OMIM databases, and generated a dominant database of candidate-discriminating sgRNAs that may specifically target the alternative allele for each dominant SNV site. Moreover, a validated database was established, which manually curated the discriminating sgRNAs that were experimentally validated in the mounting literature for multiple allele-specific purposes.