Identification and characterization of essential genes in the human genome
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Sabatini_Identification and.pdf
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Author(s)
Hughes, N. W.
Wang, Tim
Birsoy, Kivanc
Krupczak, Kevin M.
Post, Yorick
Lander, Eric Steven
Sabatini, David
Wei, Jenny J.
Date Issued
November 2015
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Wang, T. et al. “Identification and Characterization of Essential Genes in the Human Genome.” Science 350.6264 (2015): 1096–1101.
Version
Author's final manuscript
Abstract
Large-scale genetic analysis of lethal phenotypes has elucidated the molecular underpinnings of many biological processes. Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, we constructed a genome-wide single-guide RNA (sgRNA) library to
screen for genes required for proliferation and survival in a human cancer cell line. Our screen revealed the set of cell-essential genes, which was validated by an orthogonal gene-trap-based screen and comparison with yeast gene knockouts. This set is enriched for genes that encode
components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. We also uncovered a large group of uncharacterized genes involved in RNA processing, a number of whose products localize to the nucleolus. Lastly,
screens in additional cell lines showed a high degree of overlap in gene essentiality, but also revealed differences specific to each cell line and cancer type that reflect the developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure of each line. These results demonstrate the power of CRISPR-based screens and suggest a general strategy for identifying liabilities in cancer cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/science.aac7041
