Dynamic rewiring of biological activity across genotype and lineage revealed by context-dependent functional interactions.

ABSTRACT:

Background

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.

Results

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 transduc

SUBMITTER: Kim E 

PROVIDER: S-EPMC9241233 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature