BE-FF

BE-FF identifies suitable base editors for correcting single nucleotide variations (SNVs) by evaluating CRISPR/Cas and deaminase protein combinations that mediate cytidine-to-thymine (C→T) or adenosine-to-guanine (A→G) transitions and by proposing synonymous corrections that preserve the translated protein sequence.

Key Features:

• Precision in mutation correction: Locates base editors capable of direct transition corrections and identifies synonymous bystander edits that restore protein sequence without changing amino acids.
• Applicability to transversion-derived mutations: Proposes synonymous nucleotide modifications to enable correction strategies for transversion-derived pathogenic mutations that are not directly correctable by C→T or A→G edits.
• Extensive analysis of pathogenic variants: Evaluated human pathogenic point mutations and identified suitable base editors for 60.9% of transition mutations, with 19.4% of these achieved via synonymous changes, and found 298 transversion-derived pathogenic mutations potentially repairable by synonymous corrections.

Scientific Applications:

• Genomic research and therapeutic development: Supports selection of base editing strategies to correct point mutations associated with genetic disorders.
• Expansion of targetable SNVs: Enables consideration of synonymous bystander edits to broaden the set of pathogenic SNVs amenable to base editing, including some transversion-derived mutations.

Methodology:

Computationally evaluates compatibility of available base editors with specific point mutations by assessing direct transition edits and synonymous bystander alternatives to identify viable editing strategies.