title: Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies.
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.
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Cowley
authors.affiliation: Broad 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.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Weir
authors.affiliation: Broad 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.
authors.forename: Francisca
authors.initials: F
authors.lastname: Vazquez
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Scott
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Rusin
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: East-Seletsky
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Levi D
authors.initials: LD
authors.lastname: Ali
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: William Fj
authors.initials: WF
authors.lastname: Gerath
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pantel
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Lizotte
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hsiao
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Aviad
authors.initials: A
authors.lastname: Tsherniak
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dwinell
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Aoyama
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: William
authors.initials: W
authors.lastname: Harrington
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelfand
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Green
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Tomko
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Shuba
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Terence C
authors.initials: TC
authors.lastname: Wong
authors.forename: Terrence C
authors.initials: TC
authors.lastname: Wong
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Hubo
authors.initials: H
authors.lastname: Li
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Howell
authors.affiliation: Blueprint Medicines , Inc. 215 1st Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stransky
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Liefeld
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Dongkeun
authors.initials: D
authors.lastname: Jang
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bistline
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hill Meyers
authors.affiliation: Memorial Sloan Kettering , 1275 York Ave, New York, New York 10065, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Armstrong
authors.affiliation: Department of Medical, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Ken C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Broad 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.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Stegmaier
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Reich
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute , 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pellman
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Boehm
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center , Cambridge, Massachusetts 02142, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Root
authors.affiliation: Broad 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.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
mesh_terms: D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D004273:DNA, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering
chemical_list: D004273:DNA, Neoplasm; D034741:RNA, Small Interfering