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Data availability

This study used data generated by the The Cancer Genome Atlas (TCGA, a collection of publicly available data from human tissues; http://cancergenome.nih.gov/). We ran dN/dS analyses on the data from TCGA, using published CaVeMan19,20 single-nucleotide variant calls, and ASCAT21 copy number calls, as described in Martincorena et al.13. Simulation data can be reproduced by using the R and Java scripts provided.

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Acknowledgements

This work was supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001202), the UK Medical Research Council (FC001202) and the Wellcome Trust (FC001202) (M.T. and P.V.L.). M.T. is supported as a postdoctoral fellow by the European Union’s Horizon 2020 research and innovation program (Marie Skłodowska-Curie Grant agreement no. 747852-SIOMICS). P.V.L. is a Winton Group Leader in recognition of the Winton Charitable Foundation’s support toward the establishment of The Francis Crick Institute. I.M. is funded by a Cancer Research UK Career Development Fellowship (C57387/A21777). D.C.W. is funded by the Li Ka Shing Foundation. This work was supported by grant 1U24CA210957 to P.T.S.. F.M. acknowledges support from the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. Parts of this work were funded by Cancer Research UK core grant C14303/A17197 (F.M.). This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the UK Medical Research Council (grant no. MR/L016311/1) (M.T. and P.V.L.). Parts of the results published here are based on data generated by the TCGA Research Network (http://cancergenome.nih.gov/).

Author information

Author notes

  1. A list of members and affiliations appears at the end of the paper.

Affiliations

  1. The Francis Crick Institute, London, UK

    • Maxime Tarabichi
    • , Stefan C. Dentro
    • , Clemency Jolly
    • , Kerstin Haase
    • , Maxime Tarabichi
    • , Jonas Demeulemeester
    • , Matthew Fittall
    • , Peter Van Loo
    •  & Peter Van Loo
  2. Wellcome Trust Sanger Institute, Cambridge, UK

    • Maxime Tarabichi
    • , Iñigo Martincorena
    • , Stefan C. Dentro
    • , Maxime Tarabichi
    • , David J. Adams
    • , Peter J. Campbell
    • , Kevin J. Dawson
    • , Henry Lee-Six
    • , Iñigo Martincorena
    • , Thomas J. Mitchell
    •  & Ignacio Vázquez-García
  3. European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

    • Moritz Gerstung
    • , Moritz Gerstung
    • , Santiago Gonzalez
    •  & Lara Jerman
  4. Department of Life Sciences, Imperial College London, London, UK

    • Armand M. Leroi
  5. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK

    • Florian Markowetz
    • , Geoff Macintyre
    • , Ruben M. Drews
    • , Florian Markowetz
    •  & Ke Yuan
  6. Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA

    • Pavana Anur
    • , Myron Peto
    • , Paul T. Spellman
    •  & Paul T. Spellman
  7. Donnelly Centre, University of Toronto and Vector Institute, Toronto, Ontario, Canada

    • Quaid D. Morris
  8. Department of Informatics and Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway

    • Ole Christian Lingjærde
  9. Big Data Institute, University of Oxford, Oxford, UK

    • Stefan C. Dentro
    • , David C. Wedge
    •  & David C. Wedge
  10. Oxford NIHR Biomedical Research Centre, Oxford, UK

    • David C. Wedge
    •  & David C. Wedge
  11. Department of Human Genetics, University of Leuven, Leuven, Belgium

    • Peter Van Loo
    •  & Peter Van Loo
  12. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Ignaty Leshchiner
    • , Rameen Beroukhim
    • , Gad Getz
    • , Gavin Ha
    • , Dimitri G. Livitz
    • , Daniel Rosebrock
    •  & Steven Schumacher
  13. University of Toronto, Toronto, Ontario, Canada

    • Jeff Wintersinger
    • , Amit G. Deshwar
    • , Yulia Rubanova
    • , Paul C. Boutros
    • , Ruian Shi
    • , Shankar Vembu
    •  & Quaid D. Morris
  14. Vector Institute, Toronto, Ontario, Canada

    • Jeff Wintersinger
    • , Amit G. Deshwar
    • , Yulia Rubanova
    •  & Quaid D. Morris
  15. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Kaixian Yu
    • , Shaolong Cao
    • , Yu Fan
    • , Seung Jun Shin
    • , Hongtu Zhu
    •  & Wenyi Wang
  16. Dana-Farber Cancer Institute, Boston, MA, USA

    • Rameen Beroukhim
  17. Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    • Paul C. Boutros
    • , Adriana Salcedo
    •  & Lincoln D. Stein
  18. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    • David D. Bowtell
    • , Elizabeth L. Christie
    •  & Dale W. Garsed
  19. University of Melbourne, Melbourne, Victoria, Australia

    • Elizabeth L. Christie
    • , Marek Cmero
    •  & Dale W. Garsed
  20. Walter and Eliza Hall Institute, Melbourne, Victoria, Australia

    • Marek Cmero
  21. University of Cologne, Cologne, Germany

    • Yupeng Cun
    • , Martin Peifer
    •  & Tsun-Po Yang
  22. University of Leuven, Leuven, Belgium

    • Jonas Demeulemeester
  23. Simon Fraser University, Burnaby, British Columbia, Canada

    • Nilgun Donmez
    •  & Salem Malikic
  24. Vancouver Prostate Centre, Vancouver, British Columbia, Canada

    • Nilgun Donmez
    • , Salem Malikic
    •  & S. Cenk Sahinalp
  25. German Cancer Research Center (DKFZ), Heidelberg, Germany

    • Roland Eils
    • , Kortine Kleinheinz
    •  & Matthias Schlesner
  26. Heidelberg University, Heidelberg, Germany

    • Roland Eils
    •  & Kortine Kleinheinz
  27. Massachusetts General Hospital Center for Cancer Research, Charlestown, MA, USA

    • Gad Getz
  28. Massachusetts General Hospital, Department of Pathology, Boston, MA, USA

    • Gad Getz
  29. Harvard Medical School, Boston, MA, USA

    • Gad Getz
  30. Weill Cornell Medicine, New York, NY, USA

    • Marcin Imielinski
    •  & Xiaotong Yao
  31. New York Genome Center, New York, NY, USA

    • Marcin Imielinski
    •  & Xiaotong Yao
  32. University of Ljubljana, Ljubljana, Slovenia

    • Lara Jerman
  33. NorthShore University HealthSystem, Evanston, IL, USA

    • Yuan Ji
    •  & Subhajit Sengupta
  34. University of Chicago, Chicago, IL, USA

    • Yuan Ji
  35. University of California Santa Cruz, Santa Cruz, CA, USA

    • Juhee Lee
  36. University of Cambridge, Cambridge, UK

    • Thomas J. Mitchell
    •  & Ignacio Vázquez-García
  37. University of Helsinki, Helsinki, Finland

    • Ville Mustonen
  38. Carleton College, Northfield, MN, USA

    • Layla Oesper
  39. Princeton University, Princeton, NJ, USA

    • Benjamin J. Raphael
  40. Indiana University, Bloomington, IN, USA

    • S. Cenk Sahinalp
  41. Korea University, Seoul, Republic of Korea

    • Seung Jun Shin
  42. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    • David A. Wheeler
  43. University of Glasgow, Glasgow, UK

    • Ke Yuan

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Consortia

  1. The PCAWG Evolution and Heterogeneity Working Group

Contributions

M.T., I.M., M.G., A.M.L., F.M., P.T.S., Q.D.M., O.C.L., D.C.W. and P.V.L. participated in argumentation. M.T., O.C.L., D.C.W. and P.V.L. derived the deterministic equations. M.T. wrote the code and generated the figures, with input from I.M., M.G., O.C.L., D.C.W. and P.V.L.; M.T., O.C.L., D.C.W. and P.V.L. drafted the manuscript, which was revised by I.M., M.G., A.M.L., F.M., P.T.S. and Q.D.M. All authors read and approved the manuscript.

Corresponding author

Correspondence to Peter Van Loo.

Supplementary information

  1. Supplementary Text and Figures

    Supplementary Note and Supplementary Figures 1–3

  2. Reporting Summary

  3. Supplementary Software

About this article

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Published

DOI

https://doi.org/10.1038/s41588-018-0258-x

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