A Comprehensive Assessment of Somatic Mutation Calling in Cancer Genomes
| Autor: | Marc Dabad, John Douglas Mcpherson, Xose S. Puente, Liu Xi, Ivo Gut, Anne-Marie Patch, Semin Lee, Cyriac Kandoth, Ruben M. Drews, Charlotte Anderson, Eivind Hovig, Paul C. Boutros, Peter J. Campbell, Louis Letourneau, Paolo Ribeca, Hidewaki Nakagawa, Natalie Jäger, Daniel Vodak, Thomas J. Hudson, Anne Sophie Sertier, Pablo H. Hennings-Yeomans, John Zhang, Philip Ginsbach, Laurie Tonon, Emanuele Raineri, Sahil Seth, Sophia Derdak, Benedikt Brors, David T. W. Jones, Minghui He, Sergi Beltran, Rafael Valdés-Mas, David Torrents, Singer Ma, Myron Peto, Nagarajan Paramasivam, Matthew D. Eldridge, Robert E. Denroche, Paul T. Spellman, Francesc Castro Giner, Roland Eils, Timothy Beck, Sigve Nakken, Daniela S. Gerhard, Lawrence E. Heisler, Jared T. Simpson, Víctor Quesada, Rolf Kabbe, Andy G. Lynch, Patrick S. Tarpey, Lawrence Bower, Akihiro Fujimoto, Barbara Hutter, Matthias Schlesner, Marta Gut, Ivo Buchhalter, David A. Wheeler, Takafumi N. Yamaguchi, Simon Heath, Nicholas J. Harding, Tyler Alioto |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetics
Whole genome sequencing 0303 health sciences Concordance Cancer Genomics Computational biology Biology medicine.disease Genome DNA sequencing 03 medical and health sciences 0302 clinical medicine Germline mutation 030220 oncology & carcinogenesis Mutation (genetic algorithm) medicine 030304 developmental biology |
| DOI: | 10.1101/012997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|