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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pantel, Sasha 
Green, Thomas 

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.

Description

Keywords

Antineoplastic Agents, Biomarkers, Tumor, CRISPR-Cas Systems, Cell Line, Tumor, Datasets as Topic, Drug Screening Assays, Antitumor, Gene Expression Profiling, Genes, Essential, Genomics, Humans, Molecular Targeted Therapy, Neoplasms, Oncogenes, Precision Medicine, Reproducibility of Results, Small Molecule Libraries

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC