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

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• dc.contributor.author Alioto, Tyler
• dc.contributor.author Derdak, Sophia
• dc.contributor.author Ribeca, Paolo
• dc.contributor.author Castro Giner, Francesc
• dc.contributor.author Beltran, Sergi
• dc.contributor.author Raineri, Emanuele
• dc.contributor.author Dabad, Marc
• dc.contributor.author Heath, Simon
• dc.contributor.author Gut, Marta
• dc.contributor.author Gut, Ivo Glynne
• dc.date.accessioned 2023-02-13T08:54:50Z
• dc.date.available 2023-02-13T08:54:50Z
• dc.date.issued 2015
• dc.description Includes supplementary materials: online appendix; replication file
• dc.description.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.
• dc.description.sponsorship We thank the DKFZ Genomics and Proteomics Core Facility and the OICR Genome Technologies Platform for provision of sequencing services. Financial support was provided by the consortium projects READNA under grant agreement FP7 Health-F4-2008-201418, ESGI under grant agreement 262055, GEUVADIS under grant agreement 261123 of the European Commission Framework Programme 7, ICGC-CLL through the Spanish Ministry of Science and Innovation (MICINN), the Instituto de Salud Carlos III (ISCIII) and the Generalitat de Catalunya. Additional financial support was provided by the PedBrain Tumor Project contributing to the ICGC, funded by German Cancer Aid (109252) and by the German Federal Ministry of Education and Research (BMBF, grants #01KU1201A, MedSys #0315416C and NGFNplus #01GS0883), the BMBF-funded ICGC projects on early-onset prostate cancer and malignant lymphoma (#01KU1001A, #01KU1002B) and via the BMBF-funded de.NBI HD-HuB network (#031A537A, #031A537C); the Ontario Institute for Cancer Research to PCB and JDM through funding provided by the Government of Ontario, Ministry of Research and Innovation; Genome Canada; the Canada Foundation for Innovation and Prostate Cancer Canada with funding from the Movember Foundation (PCB). P.C.B. was also supported by a Terry Fox Research Institute New Investigator Award, a CIHR New Investigator Award and a Genome Canada Large-Scale Applied Project Contract. The Synergie Lyon Cancer platform has received support from the French National Institute of Cancer (INCa) and from the ABS4NGS ANR project (ANR-11-BINF-0001-06). The ICGC RIKEN study was supported partially by RIKEN President’s Fund 2011, and the supercomputing resource for the RIKEN study was provided by the Human Genome Center, University of Tokyo. M.D.E., L.B., A.G.L. and C.L.A. were supported by Cancer Research UK, the University of Cambridge and Hutchison-Whampoa Limited. S.D. is supported by the Torres Quevedo subprogramme (MICINN) under grant agreement PTQ-12-05391. E.H. is supported by the Research Council of Norway under grant agreements 221580 and 218241 and by the Norwegian Cancer Society under grant agreement 71220—PR-2006-0433. We specially thank Jennifer Jennings for administrating the activity of the ICGC Verification Working Group and Anna Borrell for administrative support.
• dc.format.mimetype application/pdf
• dc.identifier.citation Alioto TS, Buchhalter I, Derdak S, Hutter B, Eldridge MD, Hovig E, et al. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nat Commun. 2015 Dec 9;6:10001. DOI: 10.1038/ncomms10001
• dc.identifier.doi http://dx.doi.org/10.1038/ncomms10001
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/55733
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Communications. 2015 Dec 9;6:10001
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201418
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/262055
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261123
• dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cancer genetics
• dc.subject.keyword DNA sequencing
• dc.subject.keyword Genome informatics
• dc.subject.keyword Mutation
• dc.title A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion