Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells.
Abstract
The CRISPR-Cas9 system has revolutionized gene editing both at single genes and in
multiplexed loss-of-function screens, thus enabling precise genome-scale identification
of genes essential for proliferation and survival of cancer cells. However, previous
studies have reported that a gene-independent antiproliferative effect of Cas9-mediated
DNA cleavage confounds such measurement of genetic dependency, thereby leading to
false-positive results in copy number-amplified regions. We developed CERES, a computational
method to estimate gene-dependency levels from CRISPR-Cas9 essentiality screens while
accounting for the copy number-specific effect. In our efforts to define a cancer
dependency map, we performed genome-scale CRISPR-Cas9 essentiality screens across
342 cancer cell lines and applied CERES to this data set. We found that CERES decreased
false-positive results and estimated sgRNA activity for both this data set and previously
published screens performed with different sgRNA libraries. We further demonstrate
the utility of this collection of screens, after CERES correction, for identifying
cancer-type-specific vulnerabilities.
Type
Journal articleSubject
Cell Line, TumorHumans
Neoplasms
Genetic Predisposition to Disease
Sensitivity and Specificity
Reproducibility of Results
Computational Biology
Gene Dosage
Algorithms
Models, Genetic
DNA Copy Number Variations
CRISPR-Cas Systems
Permalink
https://hdl.handle.net/10161/22386Published Version (Please cite this version)
10.1038/ng.3984Publication Info
Meyers, Robin M; Bryan, Jordan G; McFarland, James M; Weir, Barbara A; Sizemore, Ann
E; Xu, Han; ... Tsherniak, Aviad (2017). Computational correction of copy number effect improves specificity of CRISPR-Cas9
essentiality screens in cancer cells. Nature genetics, 49(12). pp. 1779-1784. 10.1038/ng.3984. Retrieved from https://hdl.handle.net/10161/22386.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Jordan Bryan
Student

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info