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

Nat Commun. 2019 Dec 20;10(1):5817. doi: 10.1038/s41467-019-13805-y.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • CRISPR-Cas Systems / genetics*
  • Cell Line, Tumor
  • Datasets as Topic
  • Drug Screening Assays, Antitumor / methods*
  • Gene Expression Profiling
  • Genes, Essential / drug effects
  • Genes, Essential / genetics
  • Genomics / methods*
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Oncogenes / drug effects
  • Oncogenes / genetics
  • Precision Medicine / methods
  • Reproducibility of Results
  • Small Molecule Libraries / pharmacology


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Small Molecule Libraries