1. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies.
- Author
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Cowley GS, Weir BA, Vazquez F, Tamayo P, Scott JA, Rusin S, East-Seletsky A, Ali LD, Gerath WF, Pantel SE, Lizotte PH, Jiang G, Hsiao J, Tsherniak A, Dwinell E, Aoyama S, Okamoto M, Harrington W, Gelfand E, Green TM, Tomko MJ, Gopal S, Wong TC, Li H, Howell S, Stransky N, Liefeld T, Jang D, Bistline J, Hill Meyers B, Armstrong SA, Anderson KC, Stegmaier K, Reich M, Pellman D, Boehm JS, Mesirov JP, Golub TR, Root DE, and Hahn WC
- Subjects
- Cell Line, Tumor, DNA, Neoplasm, Genomics, Humans, Neoplasms genetics, Neoplasms pathology, RNA, Small Interfering, Cell Lineage genetics, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Mutation
- Abstract
Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features.
- Published
- 2014
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