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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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 Jäger, Philip Ginsbach, Ruben Drews, Nagarajan Paramasivam, Rolf Kabbe, Sasithorn Chotewutmontri, Nicolle Diessl, Christopher Previti, Sabine Schmidt, Benedikt Brors, Lars Feuerbach, Michael Heinold, Susanne Gröbner, 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, Víctor Quesada, Rafael Valdés-Mas, Sigve Nakken, Daniel Vodák, 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 Létourneau, Singer Ma, Sahil Seth, David Torrents, Liu Xi, David A Wheeler, Carlos López-Otín, Elías 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

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. More... »

PAGES

10001

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms10001

    DOI

    http://dx.doi.org/10.1038/ncomms10001

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045775183

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26647970


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