Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies
Posted on 2014-09-25 - 08:00
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.
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C. Hahn, William; S Cowley, Glenn; A Weir, Barbara; Vazquez, Francisca; Tamayo, Pablo; A Scott, Justine; et al. (2014). Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. figshare. Collection. https://doi.org/10.6084/m9.figshare.1019859
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AUTHORS (38)
WC
William C. Hahn
GS
Glenn S Cowley
BA
Barbara A Weir
FV
Francisca Vazquez
PT
Pablo Tamayo
JA
Justine A Scott
SR
Scott Rusin
AE
Alexandra East
LD
Levi D Ali
WF
William FJ Gerath
SE
Sarah E Pantel
PH
Patrick H Lizotte
GJ
Guozhi Jiang
JH
Jessica Hsiao
AT
Aviad Tsherniak
ED
Elizabeth Dwinell
SA
Simon Aoyama
MO
Michael Okamoto
WH
William Harrington
EG
Ellen Gelfand