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Nat Commun DOI:10.1038/s41467-019-13805-y

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

Publication TypeJournal Article
Year of Publication2019
AuthorsDempster, 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
JournalNat Commun
Date Published2019 Dec 20

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.


Alternate JournalNat Commun
PubMed ID31862961
PubMed Central IDPMC6925302
Grant List206194 / / Wellcome Trust (Wellcome) /
IUT 34-4 / / Eesti Teadusagentuur (Estonian Research Council) /
U01 CA176058 / / H. L. Snyder Medical Foundation (HL Snyder Medical Foundation) /
U01 CA199253 / / H. L. Snyder Medical Foundation (HL Snyder Medical Foundation) /
IUT 34-4 / / Ministry of Education and Research | Estonian Research Competency Council (Research Competency Council) /