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The authors performed a large-scale, image-based pooled CRISPR screen of 5,072 essential genes in human cells. The screen revealed a wide range of phenotypic defects in cells with knockouts of essential genes, including changes in nuclear morphology, cell size, DNA damage response, cytoskeletal structures, cell cycle stage, and mitotic chromosome alignment.
The paper then used multi-dimensional clustering to identify 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. Creating a resource for the phenotypic analysis of core cellular processes and defines the functional landscape of essential human genes.
The authors also found that essential genes are often co-functional, meaning that they work together to carry out a particular cellular process. Providing new insights into the molecular basis of cellular function and could be used to identify new targets for therapeutic interventions.
https://www.biorxiv.org/content/biorxiv/early/2021/11/28/2021.11.28.470116.full.pdf