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Computational approaches to identify functional genetic variants in cancer genomes

Nature Methods volume 10, pages 723–729 (2013)Cite this article

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Abstract

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype.

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Figure 1: Scheme depicting the three main approaches routinely used in the analysis of cancer somatic mutations.

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Author information

Author notes

  1. Abel Gonzalez-Perez, Ville Mustonen, Boris Reva and Graham R S Ritchie: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Unit on Biomedical Informatics, University Pompeu Fabra, Barcelona, Spain

    Abel Gonzalez-Perez & Nuria Lopez-Bigas

  2. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Ville Mustonen, Graham R S Ritchie, Adam Butler & Serge Dronov

  3. Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Boris Reva & Chris Sander

  4. Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Graham R S Ritchie & Paul Flicek

  5. Department of Systems Biology, Cellular Signal Integration Group, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark

    Pau Creixell & Rune Linding

  6. Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland, USA

    Rachel Karchin & Hannah Carter

  7. Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain

    Miguel Vazquez & Alfonso Valencia

  8. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, Queensland, Australia

    J Lynn Fink, Karin S Kassahn & John V Pearson

  9. The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada

    Gary D Bader, Jüri Reimand & Lincoln D Stein

  10. Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    Paul C Boutros, Lakshmi Muthuswamy & B F Francis Ouellette

  11. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Paul C Boutros & Lakshmi Muthuswamy

  12. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

    Paul C Boutros

  13. Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada

    B F Francis Ouellette

  14. Division of Cancer Genomics, National Cancer Center, Chuo-ku, Tokyo, Japan

    Tatsuhiro Shibata

  15. Spanish National Bioinformatics Institute, Madrid, Spain

    Alfonso Valencia

  16. Cambridge Research Institute, Cambridge, UK

    Nick B Shannon

  17. The Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA

    Li Ding

  18. Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA

    Li Ding

  19. Department of Biomolecular Engineering, University of California, Santa Cruz, California, USA

    Josh M Stuart

  20. Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California, USA

    Josh M Stuart

  21. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

    Lincoln D Stein

  22. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

    Nuria Lopez-Bigas

Consortia

the International Cancer Genome Consortium Mutation Pathways and Consequences Subgroup of the Bioinformatics Analyses Working Group

  • Abel Gonzalez-Perez
  • , Ville Mustonen
  • , Boris Reva
  • , Graham R S Ritchie
  • , Pau Creixell
  • , Rachel Karchin
  • , Miguel Vazquez
  • , J Lynn Fink
  • , Karin S Kassahn
  • , John V Pearson
  • , Gary D Bader
  • , Paul C Boutros
  • , Lakshmi Muthuswamy
  • , B F Francis Ouellette
  • , Jüri Reimand
  • , Rune Linding
  • , Tatsuhiro Shibata
  • , Alfonso Valencia
  • , Adam Butler
  • , Serge Dronov
  • , Paul Flicek
  • , Nick B Shannon
  • , Hannah Carter
  • , Li Ding
  • , Chris Sander
  • , Josh M Stuart
  • , Lincoln D Stein
  •  & Nuria Lopez-Bigas

Corresponding authors

Correspondence to Lincoln D Stein or Nuria Lopez-Bigas.

Ethics declarations

Competing interests

The author declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 2–4 (PDF 178 kb)

Supplementary Table 1

Sequence Ontology (SO) terms used to describe the effect of mutations. (XLSX 10 kb)

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the International Cancer Genome Consortium Mutation Pathways and Consequences Subgroup of the Bioinformatics Analyses Working Group. Computational approaches to identify functional genetic variants in cancer genomes. Nat Methods 10, 723–729 (2013). https://doi.org/10.1038/nmeth.2562

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