RT Journal Article
SR Electronic
T1 A Comprehensive Assessment of Somatic Mutation Calling in Cancer Genomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 012997
DO 10.1101/012997
A1 Tyler S. Alioto
A1 Sophia Derdak
A1 Timothy A. Beck
A1 Paul C. Boutros
A1 Lawrence Bower
A1 Ivo Buchhalter
A1 Matthew D. Eldridge
A1 Nicholas J Harding
A1 Lawrence E. Heisler
A1 Eivind Hovig
A1 David T. W. Jones
A1 Andrew G. Lynch
A1 Sigve Nakken
A1 Paolo Ribeca
A1 Anne-Sophie Sertier
A1 Jared T. Simpson
A1 Paul Spellman
A1 Patrick Tarpey
A1 Laurie Tonon
A1 Daniel Vodák
A1 Takafumi N. Yamaguchi
A1 Sergi Beltran Agullo
A1 Marc Dabad
A1 Robert E. Denroche
A1 Philip Ginsbach
A1 Simon C. Heath
A1 Emanuele Raineri
A1 Charlotte L. Anderson
A1 Benedikt Brors
A1 Ruben Drews
A1 Roland Eils
A1 Akihiro Fujimoto
A1 Francesc Castro Giner
A1 Minghui He
A1 Pablo Hennings-Yeomans
A1 Barbara Hutter
A1 Natalie Jäger
A1 Rolf Kabbe
A1 Cyriac Kandoth
A1 Semin Lee
A1 Louis Létourneau
A1 Singer Ma
A1 Hidewaki Nakagawa
A1 Nagarajan Paramasivam
A1 Anne-Marie Patch
A1 Myron Peto
A1 Matthias Schlesner
A1 Sahil Seth
A1 David Torrents
A1 David A. Wheeler
A1 Liu Xi
A1 John Zhang
A1 Daniela S. Gerhard
A1 Víctor Quesada
A1 Rafael Valdés-Mas
A1 Marta Gut
A1 Thomas J. Hudson
A1 John D. McPherson
A1 Xose S. Puente
A1 Ivo G. Gut
YR 2014
UL http://biorxiv.org/content/early/2014/12/24/012997.abstract
AB The emergence of next generation DNA sequencing technology is enabling high-resolution cancer genome analysis. Large-scale projects like the International Cancer Genome Consortium (ICGC) are systematically scanning cancer genomes to identify recurrent somatic mutations. Second generation DNA sequencing, however, is still an evolving technology and procedures, both experimental and analytical, are constantly changing. Thus the research community is still defining a set of best practices for cancer genome data analysis, with no single protocol emerging to fulfil this role. Here we describe an extensive benchmark exercise to identify and resolve issues of somatic mutation calling. Whole genome sequence datasets comprising tumor-normal pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, were shared within the ICGC and submissions of somatic mutation calls were compared to verified mutations and to each other. Varying strategies to call mutations, incomplete awareness of sources of artefacts, and even lack of agreement on what constitutes an artefact or real mutation manifested in widely varying mutation call rates and somewhat low concordance among submissions. We conclude that somatic mutation calling remains an unsolved problem. However, we have identified many issues that are easy to remedy that are presented here. Our study highlights critical issues that need to be addressed before this valuable technology can be routinely used to inform clinical decision-making.SSMSomatic Single-base Mutations or Simple Somatic Mutations, refers to a somatic single base changeSIMSomatic Insertion/deletion MutationCNVCopy Number VariantSVStructural VariantSNPSingle Nucleotide Polymorphisms, refers to a single base variable position in the germline with a frequency of > 1% in the general populationCLLChronic Lymphocytic LeukaemiaMBMedulloblastomaICGCInternational Cancer Genome ConsortiumBMBenchmarkAbbreviations and Definitionsaligner = mapper, these terms are used interchangeably