A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing

Tyler S. Alioto, Ivo Buchhalter, Sophia Derdak, Barbara Hutter, Matthew D. Eldridge, Eivind Hovig, Lawrence E. Heisler, Timothy A. Beck, Jared T. Simpson, Laurie Tonon, Anne-Sophie Sertier, Ann-Marie Patch, Natalie Jaeger, Philip Ginsbach, Ruben Drews, Nagarajan Paramasivam, Rolf Kabbe, Sasithorn Chotewutmontri, Nicolle Diessl, Christopher PrevitiSabine Schmidt, Benedikt Brors, Lars Feuerbach, Michael Heinold, Susanne Groebner, Andrey Korshunov, Patrick S. Tarpey, Adam P. Butler, Jonathan Hinton, David Jones, Andrew Menzies, Keiran Raine, Rebecca Shepherd, Lucy Stebbings, Jon W. Teague, Paolo Ribeca, Francesc Castro Giner, Sergi Beltran, Emanuele Raineri, Marc Dabad, Simon C. Heath, Marta Gut, Robert E. Denroche, Nicholas J. Harding, Takafumi N. Yamaguchi, Akihiro Fujimoto, Hidewaki Nakagawa, Ctor Quesada, Rafael Valdes-Mas, Sigve Nakken, Daniel Vodak, Lawrence Bower, Andrew G. Lynch, Charlotte L. Anderson, Nicola Waddell, John V. Pearson, Sean M. Grimmond, Myron Peto, Paul Spellman, Minghui He, Cyriac Kandoth, Semin Lee, John Zhang, Louis Letourneau, Singer Ma, Sahil Seth, David Torrents, Liu Xi, David A. Wheeler, Carlos Lopez-Otin, Elias Campo, Peter J. Campbell, Paul C. Boutros, Xose S. Puente, Daniela S. Gerhard, Stefan M. Pfister, John D. McPherson, Thomas J. Hudson, Matthias Schlesner, Peter Lichter, Roland Eils, David T. W. Jones, Ivo G. Gut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

218 Citations (Scopus)
2 Downloads (Pure)


As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to similar to 100 x shows benefits, as long as the tumour: control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.

Original languageEnglish
Article number10001
Number of pages13
JournalNature Communications
Publication statusPublished - 9 Dec 2015


  • Cancer genetics
  • DNA sequencing
  • Genome informatics
  • Mutation


Dive into the research topics of 'A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing'. Together they form a unique fingerprint.
  • A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing (dataset)

    Alioto, T. S. (Creator), Buchhalter, I. (Creator), Derdak, S. (Creator), Hutter, B. (Creator), Eldridge, M. D. (Creator), Hovig, E. (Creator), Heisler, L. E. (Creator), Beck, T. A. (Creator), Simpson, J. T. (Creator), Tonon, L. (Creator), Sertier, A. (Creator), Patch, A. (Creator), Jaeger, N. (Creator), Ginsbach, P. (Creator), Drews, R. (Creator), Paramasivam, N. (Creator), Kabbe, R. (Creator), Chotewutmontri, S. (Creator), Diessl, N. (Creator), Previti, C. (Creator), Schmidt, S. (Creator), Brors, B. (Creator), Feuerbach, L. (Creator), Heinold, M. (Creator), Groebner, S. (Creator), Korshunov, A. (Creator), Tarpey, P. S. (Creator), Butler, A. P. (Creator), Hinton, J. (Creator), Jones, D. (Creator), Menzies, A. (Creator), Raine, K. (Creator), Shepherd, R. (Creator), Stebbings, L. (Creator), Teague, J. W. (Creator), Ribeca, P. (Creator), Castro Giner, F. (Creator), Beltran, S. (Creator), Raineri, E. (Creator), Dabad, M. (Creator), Heath, S. C. (Creator), Gut, M. (Creator), Denroche, R. E. (Creator), Harding, N. J. (Creator), Yamaguchi, T. N. (Creator), Fujimoto, A. (Creator), Nakagawa, H. (Creator), Quesada, C. (Creator), Valdes-Mas, R. (Creator), Nakken, S. (Creator), Vodak, D. (Creator), Bower, L. (Creator), Lynch, A. (Creator), Anderson, C. L. (Creator), Waddell, N. (Creator), Pearson, J. V. (Creator), Grimmond, S. M. (Creator), Peto, M. (Creator), Spellman, P. (Creator), He, M. (Creator), Kandoth, C. (Creator), Lee, S. (Creator), Zhang, J. (Creator), Letourneau, L. (Creator), Ma, S. (Creator), Seth, S. (Creator), Torrents, D. (Creator), Xi, L. (Creator), Wheeler, D. A. (Creator), Lopez-Otin, C. (Creator), Campo, E. (Creator), Campbell, P. J. (Creator), Boutros, P. C. (Creator), Puente, X. S. (Creator), Gerhard, D. S. (Creator), Pfister, S. M. (Creator), McPherson, J. D. (Creator), Hudson, T. J. (Creator), Schlesner, M. (Creator), Lichter, P. (Creator), Eils, R. (Creator), Jones, D. T. W. (Creator) & Gut, I. G. (Creator), European Genome-phenome Archive (EGA), 2015


Cite this