High degree of polyclonality hinders somatic mutation calling in lung brush samples of COPD cases and controls

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• dc.contributor.author Thun, Gian Andri
• dc.contributor.author Derdak, Sophia
• dc.contributor.author Castro Giner, Francesc
• dc.contributor.author Apunte Ramos, Katherine
• dc.contributor.author Águeda, Lidia
• dc.contributor.author Gut, Marta
• dc.contributor.author Gut, Ivo Glynne
• dc.date.accessioned 2020-04-08T07:08:31Z
• dc.date.available 2020-04-08T07:08:31Z
• dc.date.issued 2019
• dc.description.abstract Chronic obstructive pulmonary disease (COPD) is induced by cigarette smoking and characterized by inflammation of airway tissue. Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n = 8), as well as from ex-smokers with variable degrees of COPD (n = 4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data. However, consensus calls showed little promise of representing true positives due to low mappability of corresponding sequence reads and high overlap with positions harbouring known genetic polymorphisms. A targeted re-sequencing approach suggested that only few mutations would survive stringent verification testing and that our data did not allow the inference of any difference in the mutational load of bronchial brush samples between former smoking COPD cases and controls. High polyclonality in airway brush samples renders medium-depth sequencing insufficient to provide the resolution to detect somatic mutations. Deep sequencing data of airway biopsies are needed to tackle the question.
• dc.format.mimetype application/pdf
• dc.identifier.citation Thun GA, Derdak S, Castro-Giner F, Apunte-Ramos K, Águeda L, Wjst M et al. High degree of polyclonality hinders somatic mutation calling in lung brush samples of COPD cases and controls. Sci Rep. 2019; 9(1):20158. DOI: 10.1038/s41598-019-56618-1
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-019-56618-1
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/44183
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Sci Rep. 2019; 9(1):20158
• dc.rights © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 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 Chronic obstructive pulmonary disease
• dc.subject.keyword Genome
• dc.title High degree of polyclonality hinders somatic mutation calling in lung brush samples of COPD cases and controls
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion