Analysis | Published:

Pharmacogenomic agreement between two cancer cell line data sets

Nature volume 528, pages 8487 (03 December 2015) | Download Citation

Abstract

Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases.

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Acknowledgements

We thank T. Golub, E. Lander, S. Schreiber, P. Clemons and J. Engelman for helpful discussions. This work was supported by research grants from the Novartis Institutes for BioMedical Research (CCLE; L.A.G., M.G., and G.V.K.) and by grants from the Wellcome Trust (086357 and 102696; D.A.H., M.R.S., U.M., M.J.G., A.A., C.H.B.) and the National Institutes of Health (1U54HG006097-01, A.A. and C.H.B.). L.A.G. was supported in part by grants from Novartis and the Dr. Miriam and Sheldon Adelson Medical Research Foundation. G.V.K. was supported in part by the Slim Foundation. F.I. was supported in part by the EMBL-EBI and Wellcome Trust Sanger Institute Post-Doctoral (ESPOD) programme, and U.M. was funded by a Cancer Research UK Clinician Scientist Fellowship (A16629).

Author information

Author notes

    • Nicolas Stransky
    • , Joseph Lehár
    • , Manway Liu
    • , Dmitriy Sonkin
    •  & Julio Saez-Rodriguez

    Present addresses: Blueprint Medicines, 38 Sidney Street, Cambridge, Massachusetts 02139, USA (N.S.); Google Life Sciences, 1600 Amphitheatre Pkwy, Mountain View, California 94043, USA (J.L. and M.L.); National Cancer Institute, 9609 Medical Center Drive, Rockville, Maryland 20850, USA (D.S.); Joint Research Centre for Computational Biomedicine, RWTH Aachen University, Faculty of Medicine, D-52074 Aachen, Germany (J.S.-R.).

    • Nicolas Stransky
    • , Mahmoud Ghandi
    • , Joseph Lehár
    • , Arnaud Amzallag
    • , Michael P. Menden
    •  & Francesco Iorio

    These authors contributed equally to this work.

Affiliations

  1. The Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA

    • Nicolas Stransky
    • , Mahmoud Ghandi
    • , Gregory V. Kryukov
    •  & Levi A. Garraway
  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Levi A. Garraway
  3. Massachusetts General Hospital Cancer Center, 149 13th Street, Charlestown, Massachusetts 02129, USA

    • Arnaud Amzallag
    • , Iulian Pruteanu-Malinici
    • , Daniel A. Haber
    • , Sridhar Ramaswamy
    •  & Cyril H. Benes
  4. Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA

    • Joseph Lehár
    • , Manway Liu
    • , Dmitriy Sonkin
    • , Audrey Kauffmann
    • , Kavitha Venkatesan
    • , Elena J. Edelman
    • , Markus Riester
    • , Jordi Barretina
    • , Giordano Caponigro
    • , Robert Schlegel
    • , William R. Sellers
    • , Frank Stegmeier
    •  & Michael Morrissey
  5. European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton CB10 1SD, UK

    • Michael P. Menden
    • , Francesco Iorio
    •  & Julio Saez-Rodriguez
  6. Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK

    • Francesco Iorio
    • , Michael R. Stratton
    • , Ultan McDermott
    •  & Mathew J. Garnett

Consortia

  1. The Cancer Cell Line Encyclopedia Consortium

    Broad Institute

    Novartis Institutes for Biomedical Research

  2. The Genomics of Drug Sensitivity in Cancer Consortium

    Massachusetts General Hospital

    European Molecular Biology Laboratory, European Bioinformatics Institute, and Wellcome Trust Sanger Institute

Authors

    Contributions

    N.S., L.A.G., A.A., D.A.H., C.H.B., S.R., J.L., J.B., G.C., R.S., W.R.S., F.S., M.P.M., F.I., M.M., J.S.-R., M.R.S., U.M. and M.J.G. conceived the studies; N.S., M.G., G.V.K., A.A., I.P.-M., J.L., M.L., D.S., A.K., K.V., E.J.E., M.P.M., F.I. and M.M. performed analyses; N.S., M.G., A.A., M.L., M.R., F.I. and M.M. wrote/tested the R code, and N.S., M.G., A.A., L.A.G., C.H.B., J.L., M.P.M. and J.S.-R. wrote the paper. The Cancer Cell Line Encyclopedia investigators are N.S., M.G., G.V.K., L.A.G., J.L., M.L., D.S., A.K., K.V., E.J.E., M.R., J.B., G.C., R.S., W.R.S., F.S. and M.M.; the Genomics of Drug Sensitivity in Cancer investigators are A.A., I.P.-M., D.A.H., S.R., C.H.B., F.I., M.R.S., U.M. and M.J.G.

    Competing interests

    N.S. is an employee and shareholder of Blueprint Medicines. L.A.G. is a consultant for Foundation Medicine, Novartis, Boehringer Ingelheim, an equity holder in Foundation Medicine, and a member of the Scientific Advisory Board at Warp Drive. L.A.G. receives sponsored research support from Novartis. J.L., M.L., A.K., K.V., J.B., G.C., R.S., W.R.S, F.S., M.P.M. are employees and shareholders of Novartis. U.M. is a founder and consultant for 14M Genomics Ltd. M.R.S. is a founder and shareholder of 14M Genomics Ltd.

    Corresponding authors

    Correspondence to Levi A. Garraway or Cyril H. Benes.

    Extended data

    Supplementary information

    Excel files

    1. 1.

      Supplementary Data 1

      This file contains cell line collections and drug responses.

    2. 2.

      Supplementary Data 2

      This file contains Waterfall analysis.

    3. 3.

      Supplementary Data 3

      This file contains ANOVA results for gene-drug associations.

    4. 4.

      Supplementary Data 4

      This file contains t-test results for tissue-drug associations.

    5. 5.

      Supplementary Data 5

      This file contains Elastic Net results.

    6. 6.

      Supplementary Data 6

      This file contains Elastic Net and Ridge regression results.

    7. 7.

      Supplementary Data 7

      This file contains Drug/Genotype associations missed in one dataset.

    PDF files

    1. 1.

      Supplementary Text

      This file contains a Supplementary Discussion and additional references.

    About this article

    Publication history

    Received

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    Published

    DOI

    https://doi.org/10.1038/nature15736

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