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

Author:

Dempster Joshua M.ORCID,Pacini ClareORCID,Pantel Sasha,Behan Fiona M.ORCID,Green Thomas,Krill-Burger JohnORCID,Beaver Charlotte M.,Younger Scott T.,Zhivich Victor,Najgebauer Hanna,Allen Felicity,Gonçalves Emanuel,Shepherd Rebecca,Doench John G.ORCID,Yusa Kosuke,Vazquez FranciscaORCID,Parts Leopold,Boehm Jesse S.ORCID,Golub Todd R.ORCID,Hahn William C.ORCID,Root David E.ORCID,Garnett Mathew J.,Tsherniak AviadORCID,Iorio FrancescoORCID

Abstract

AbstractGenome-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.

Funder

Wellcome Trust

Eesti Teadusagentuur

H. L. Snyder Medical Foundation

Open Targets: OTAR2-055

Open Targets: OTAR015

Ministry of Education and Research | Estonian Research Competency Council

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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