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bioRxiv · 10.1101/2021.11.28.470116

The phenotypic landscape of essential human genes

Funk, L.·Su, K.-C.·Feldman, D.·Singh, A.·Moodie, B.·Blainey, P.·Cheeseman, I. M.
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Abstract

Understanding the basis for cellular growth, proliferation, and function requires determining the contributions of essential genes to diverse cellular processes. Here, we combined pooled CRISPR/Cas9-based functional screening of 5,072 fitness-conferring genes in human cells with microscopy-based visualization of DNA, DNA damage, actin, and microtubules. Analysis of >31 million individual cells revealed measurable phenotypes for >90% of genes. Using multi-dimensional clustering based on hundreds of quantitative phenotypic parameters, we identified co-functional genes across diverse cellular activities, revealing novel gene functions and associations. Pooled live-cell screening of [~]450,000 cell division events for 239 genes further identified functional contributions to chromosome segregation. Our work creates a resource for the phenotypic analysis of core cellular processes and defines the functional landscape of essential human genes.

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Funk, L., Su, K.-C., Feldman, D., Singh, A., Moodie, B., Blainey, P., Cheeseman, I. M.. 2021-11-28. The phenotypic landscape of essential human genes. https://doi.org/10.1101/2021.11.28.470116

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