A side-by-side comparison of variant function measurements using deep mutational scanning and base editing.

ABSTRACT: Variant annotation is a crucial objective in mammalian functional genomics. Deep Mutational Scanning (DMS) is a well-established method for annotating human gene variants, but CRISPR base editing (BE) is emerging as an alternative. However, questions remain about how well high-throughput base editing measurements can annotate variant function and the extent of downstream experimental validation required. This study presents the first direct comparison of DMS and BE in the same lab and cell line. Results indicate that focusing on the most likely edits and highest efficiency sgRNAs enhances the agreement between a "gold standard" DMS dataset and a BE screen. A simple filter for sgRNAs making single edits in their window could sufficiently annotate a large proportion of variants directly from

SUBMITTER: Sokirniy I 

PROVIDER: S-EPMC11244880 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature