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

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms10001

2041-1723

Tyler Alioto, Ivo Buchhalter, Sophia Derdak, Barbara Hutter, Matthew Eldridge, Eivind Hovig, Lawrence E. Heisler, Timothy A. Beck, Jared T. Simpson, Laurie Tonon, Anne-Sophie Sertier, Ann‐Marie Patch, Natalie Jäger, Philip Ginsbach, Ruben M. Drews, Nagarajan Paramasivam, Rolf Kabbe, Sasithorn Chotewutmontri, Nicolle Diessl, Christopher Previti, Sabine Schmidt, Benedikt Brors, Lars Feuerbach, Michael C. Heinold, Susanne Gröbner, Andrey Korshunov, Patrick 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 Beltrán, Emanuele Raineri, Marc Dabad, Simon Heath, Marta Gut, Robert E. Denroche, Nicholas J. Harding, Takafumi N. Yamaguchi, Akihiro Fujimoto, Hidewaki Nakagawa, Vı́ctor Quesada, Rafael Valdés‐Mas, Sigve Nakken, Daniel Vodák, Lawrence Bower, Andy G. Lynch, Charlotte Anderson, Nicola Waddell, John V. Pearson, Sean M. Grimmond, Myron Peto, Paul T. Spellman, Minghui He, Cyriac Kandoth, Semin Lee, John H. Zhang, Louis Létourneau, Singer Ma, Sahil Seth, David Torrents, Xi Liu, David A. Wheeler, Carlos López‐Otín, Elı́as Campo, Peter J. Campbell, Paul C. Boutros, Xosé S. Puente, Daniela S. Gerhard, Stefan M. Pfister, John D. McPherson, Thomas J. Hudson, Matthias Schlesner, Peter Lichter, Roland Eils, David Jones, Marta Gut,

Chronic Lymphocytic Leukemia Research

Abstract 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 ∼100 × 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.