biostudies-literatureKim ECPRITNational Cancer InstituteNCI NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSAndrew Sabin Family Foundation140https://www.ebi.ac.uk/biostudies/studies/S-EPMC9241233biostudies-literatureUnknown23(1)<h4>Background</h4>Coessentiality networks derived from CRISPR screens in cell lines provide a powerful framework for identifying functional modules in the cell and for inferring the roles of uncharacterized genes. However, these networks integrate signal across all underlying data and can mask strong interactions that occur in only a subset of the cell lines analyzed.<h4>Results</h4>Here, we decipher dynamic functional interactions by identifying significant cellular contexts, primarily by oncogenic mutation, lineage, and tumor type, and discovering coessentiality relationships that depend on these contexts. We recapitulate well-known gene-context interactions such as oncogene-mutation, paralog buffering, and tissue-specific essential genes, show how mutation rewires known signal transducGenome biologyDynamic rewiring of biological activity across genotype and lineage revealed by context-dependent functional interactions.PMC9241233R35 GM130119P30 CA016672R35GM130119P30CA16672RR160032Lin CKim EHart TColic MGheorghe VBristow CABertolet LLNovak LCfalseDynamic rewiring of biological activity across genotype and lineage revealed by context-dependent functional interactions.<h4>Background</h4>Coessentiality networks derived from CRISPR screens in cell lines provide a powerful framework for identifying functional modules in the cell and for inferring the roles of uncharacterized genes. However, these networks integrate signal across all underlying data and can mask strong interactions that occur in only a subset of the cell lines analyzed.<h4>Results</h4>Here, we decipher dynamic functional interactions by identifying significant cellular contexts, primarily by oncogenic mutation, lineage, and tumor type, and discovering coessentiality relationships that depend on these contexts. We recapitulate well-known gene-context interactions such as oncogene-mutation, paralog buffering, and tissue-specific essential genes, show how mutation rewires known signal transduc2022-01-01T00:00:00Z2022 Jun2025-04-04T19:06:26.237Z2022-07-08T16:48:38.869ZS-EPMC92412333576887310.1186/s13059-022-02712-z