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FUNCTIONAL GENOMICS

Finding function with base editing screens

Nature Reviews Genetics volume 22, pages 200–201 (2021)Cite this article

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Functional characterization of genetic variants is essential to assess causality in genetic diseases including cancer. Two new studies in Cell report the use of CRISPR–Cas cytosine base editors (CBEs) in mammalian cells for high-throughput functional genomics screens.

Hanna et al. first undertook both positive selection (assessing resistance to the BRAF inhibitor vemurafenib) and negative selection (assessing viability) screens using a lentiviral library of 12,141 Streptococcus pyogenes sgRNAs targeting 47 genes in five cell lines. After benchmarking the CBEs, the authors then assayed known loss-of-function mutations in the BRCA1 and BRCA2 genes, showing high precision of the screens, with a sensitivity of 70% and 84%, and a specificity of 84% and 86%, respectively.

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References

Original articles

  • Hanna, R. E. et al. Massively parallel assessment of human variants with base editor screens. Cell 184, 1064–1080 (2021)

    Article  CAS  Google Scholar 

  • Cuella-Martin, R. et al. Functional interrogation of DNA damage response variants with base editing screens. Cell 184, 1081–1097 (2021)

    Article  CAS  Google Scholar 

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  1. Nature Reviews Genetics http://www.nature.com/nrg/

    Linda Koch

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  1. Linda Koch
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Correspondence to Linda Koch.

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Koch, L. Finding function with base editing screens. Nat Rev Genet 22, 200–201 (2021). https://doi.org/10.1038/s41576-021-00340-0

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  • DOI: https://doi.org/10.1038/s41576-021-00340-0

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