Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets.

Experimental settings and reagents used in the experimental pipelines underlying the two compared data sets.

Dempster et al. (2019) Nat Commun. CC BY 4.0

Dempster JM, Pacini C, Pantel S, Behan FM, Green T, Krill-Burger J, Beaver CM, Younger ST, Zhivich V, Najgebauer H, Allen F, Gonçalves E, Shepherd R, Doench JG, Yusa K, Vazquez F, Parts L, Boehm JS, Golub TR, Hahn WC, Root DE, Garnett MJ, Tsherniak A, Iorio F.

Nature Communications

December 20, 2019

Genome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyze data from recently published pan-cancer CRISPR-Cas9 screens performed at the Broad and Sanger Institutes. Despite significant differences in experimental protocols and reagents, we find that the screen results are highly concordant across multiple metrics with both common and specific dependencies jointly identified across the two studies. Furthermore, robust biomarkers of gene dependency found in one data set are recovered in the other. Through further analysis and replication experiments at each institute, we show that batch effects are driven principally by two key experimental parameters: the reagent library and the assay length. These results indicate that the Broad and Sanger CRISPR-Cas9 viability screens yield robust and reproducible findings.

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Last updated: December 30, 2019