Integrated Cross-study Datasets of Genetic Dependencies in Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Mar 13

PMID 33712601

Citations 134

Authors

Clare Pacini

Joshua M Dempster

Isabella Boyle

Emanuel Goncalves

Hanna Najgebauer

Emre Karakoc

Dieudonne van der Meer

Andrew Barthorpe

Howard Lightfoot

Patricia Jaaks

James M McFarland

Mathew J Garnett

Aviad Tsherniak

Francesco Iorio

Affiliations

Soon will be listed here.

Abstract

CRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human cancers and to assemble a comprehensive map of cancer genetic vulnerabilities. Here, we integrated the two largest public independent CRISPR-Cas9 screens performed to date (at the Broad and Sanger institutes) by assessing, comparing, and selecting methods for correcting biases due to heterogeneous single-guide RNA efficiency, gene-independent responses to CRISPR-Cas9 targeting originated from copy number alterations, and experimental batch effects. Our integrated datasets recapitulate findings from the individual datasets, provide greater statistical power to cancer- and subtype-specific analyses, unveil additional biomarkers of gene dependency, and improve the detection of common essential genes. We provide the largest integrated resources of CRISPR-Cas9 screens to date and the basis for harmonizing existing and future functional genetics datasets.

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