BEscreen: a versatile toolkit to design base editing libraries

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Base editing facilitates high-throughput screening of genetic variants to understand their phenotypic effects.
• Designing single guide RNA (sgRNA) libraries is crucial for gene- or variant-centric base editing screens.
• Existing computational tools lack versatility and scalability for diverse sgRNA library design needs.

Purpose of the Study:

• Introduce BEscreen, a comprehensive tool for designing base editing guide RNAs.
• Provide a versatile and scalable solution for various base editing screening approaches.
• Facilitate the design of sgRNA libraries for genetic variant analysis.

Main Methods:

• BEscreen offers web server and command-line interfaces for accessibility.
• Supports variant-centric (genomic coordinates, amino acid changes, rsIDs), gene-centric (near-saturation libraries), and region-centric (all possible guides) design modes.
• Includes options for selecting guides by biological consequence, customizing base editor characteristics, and integrating Ensembl's Variant Effect Predictor for annotation.

Main Results:

• BEscreen provides a versatile platform for designing base editing screens.
• Accommodates a wide range of screening strategies, from individual variants to large-scale libraries.
• Enables customizable and scalable sgRNA library design for phenotypic screening.

Conclusions:

• BEscreen is a highly versatile tool for designing base editing screens.
• Offers seamless scalability for diverse use cases, from single variants to saturation libraries.
• Empowers researchers to efficiently design and execute base editing screens for genetic variant analysis.