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Sci Data. 2014 Sep 30;1:140035. doi: 10.1038/sdata.2014.35. eCollection 2014.

Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies.

Author information

  • 1Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
  • 2Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA ; Department of Medical, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
  • 3Department of Pediatric Oncology, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
  • 4Blueprint Medicines , Inc. 215 1st Street, Cambridge, Massachusetts 02142, USA.
  • 5Memorial Sloan Kettering , 1275 York Ave, New York, New York 10065, USA.
  • 6Department of Medical, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
  • 7Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA ; Department of Pediatric Oncology, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
  • 8Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA ; Department of Medical, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA ; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA ; Departments of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, USA.

Erratum in

  • Sci Data. 2014;1:140044. Wong, Terrence C [corrected to Wong, Terence C].

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.

PMID:
25984343
PMCID:
PMC4432652
DOI:
10.1038/sdata.2014.35
[PubMed - indexed for MEDLINE]
Free PMC Article
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