Benchmarking genetic interaction scoring methods for identifying synthetic lethality from combinatorial CRISPR screens.

ABSTRACT: Synthetic lethality (SL) is an extreme form of negative genetic interaction, where simultaneous disruption of two non-essential genes causes cell death. SL can be exploited to develop cancer therapies that target tumour cells with specific mutations, potentially limiting toxicity. Pooled combinatorial CRISPR screens, where two genes are simultaneously perturbed and the resulting impacts on fitness estimated, are now widely used for the identification of SL targets in cancer. Various scoring methods have been developed to infer SL genetic interactions from these screens, but there has been no systematic comparison of these approaches. Here, we performed a comprehensive analysis of five scoring methods for SL detection using five combinatorial CRISPR datasets. We assessed the performance of

SUBMITTER: Ajmal H 

PROVIDER: S-EPMC12464814 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature