TY - JOUR T1 - A network of human functional gene interactions from knockout fitness screens in cancer cells JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800278 VL - 2 IS - 2 SP - e201800278 AU - Eiru Kim AU - Merve Dede AU - Walter F Lenoir AU - Gang Wang AU - Sanjana Srinivasan AU - Medina Colic AU - Traver Hart Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201800278.abstract N2 - 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. ER -