Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens.

ABSTRACT: Genetic interaction (GI) networks in model organisms have revealed how combinations of genome variants can impact phenotypes. To advance efforts toward a reference human GI network, we developed the quantitative Genetic Interaction (qGI) score, a method for precise GI measurement from genome-wide CRISPR-Cas9 screens in different query mutants constructed in a single human cell line. We found surprising prevalent systematic variation unrelated to GIs in CRISPR screen data, including both genomically linked effects and functionally coherent covariation. Leveraging ~40 control screens in wild-type cells and half a billion differential fitness effect measurements, we developed a pipeline for CRISPR screen data processing and normalization to correct these artifacts and measure accurate, quanti

SUBMITTER: Billmann M 

PROVIDER: S-EPMC12803112 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature