A network of human functional gene interactions from knockout fitness screens in cancer cells
Year: 2019
Type: article
Abstract: Genetic interactions mediate the emergence of phenotype from genotype. The systematic survey of genetic interactions in yeast showed that genes operating in the same biological process have highly correlated genetic interaction profiles, and this observation has been exploited to infer gene function in model organisms. Such assays of digenic perturbations in human cells are also highly informative, but are not scalable, even with CRISPR-mediated methods. As an alternative, we developed an indirect method of deriving functional interactions. We show that genes having correlated knockout fitness profiles across diverse, non-isogenic cell lines are analogous to genes having correlated genetic interaction profiles across isogenic query strains and similarly imply shared biological function. We constructed a network of genes with correlated fitness profiles across 276 high-quality CRISPR knockout screens in cancer cell lines into a "coessentiality network," with up to 500-fold enrichment for co-functional gene pairs, enabling strong inference of gene function and highlighting the modular organization of the cell.
Source: Life Science Alliance
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G1468253849, G178629068, G1901027039, Recruitment of First-Time, Tenure-Track Faculty Members, G293715275, G4276892241, G6736661663, G7534854087, G788993117, Deciphering the hierarchical modularity of the mammalian cell through network integration and complex genetic perturbation strategies, Cancer Center Support Grant
OpenAlex ID: W2936647581