PT  - JOURNAL ARTICLE
AU  - Eiru Kim
AU  - Merve Dede
AU  - Walter F Lenoir
AU  - Gang Wang
AU  - Sanjana Srinivasan
AU  - Medina Colic
AU  - Traver Hart
TI  - A network of human functional gene interactions from knockout fitness screens in cancer cells
AID  - 10.26508/lsa.201800278
DP  - 2019 Apr 01
TA  - Life Science Alliance
PG  - e201800278
VI  - 2
IP  - 2
4099  - https://www.life-science-alliance.org/content/2/2/e201800278.short
4100  - https://www.life-science-alliance.org/content/2/2/e201800278.full
SO  - Life Sci. Alliance2019 Apr 01; 2
AB  - 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.