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

Joshua M. Dempster, Clare Pacini, Sasha Pantel, Fiona M. Behan, Thomas Green, John Krill-Burger, Charlotte M. Beaver, Scott T. Younger, Victor Zhivich, Hanna Najgebauer, Felicity Allen, Emanuel Gonçalves, Rebecca Shepherd, John G. Doench, Kosuke Yusa, Francisca Vazquez, Leopold Parts, Jesse S. Boehm, Todd R. Golub, William C. Hahn, David E. Root, Mathew J. Garnett, Aviad Tsherniak () and Francesco Iorio ()
Additional contact information
Joshua M. Dempster: Broad Institute of MIT and Harvard
Clare Pacini: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Sasha Pantel: Broad Institute of MIT and Harvard
Fiona M. Behan: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Thomas Green: Broad Institute of MIT and Harvard
John Krill-Burger: Broad Institute of MIT and Harvard
Charlotte M. Beaver: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Scott T. Younger: Broad Institute of MIT and Harvard
Victor Zhivich: Broad Institute of MIT and Harvard
Hanna Najgebauer: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Felicity Allen: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Emanuel Gonçalves: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Rebecca Shepherd: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
John G. Doench: Broad Institute of MIT and Harvard
Kosuke Yusa: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Francisca Vazquez: Broad Institute of MIT and Harvard
Leopold Parts: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Jesse S. Boehm: Broad Institute of MIT and Harvard
Todd R. Golub: Broad Institute of MIT and Harvard
William C. Hahn: Broad Institute of MIT and Harvard
David E. Root: Broad Institute of MIT and Harvard
Mathew J. Garnett: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Aviad Tsherniak: Broad Institute of MIT and Harvard
Francesco Iorio: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13805-y

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