High degree of polyclonality hinders somatic mutation calling in lung brush samples of COPD cases and controls.
Aged
Biomarkers
Biopsy
Cigarette Smoking
/ adverse effects
Computational Biology
DNA Mutational Analysis
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Lung
/ metabolism
Male
Middle Aged
Mutation
Pulmonary Disease, Chronic Obstructive
/ diagnosis
Reproducibility of Results
Respiratory Function Tests
Risk Factors
Severity of Illness Index
Whole Genome Sequencing
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 12 2019
27 12 2019
Historique:
received:
11
01
2019
accepted:
04
12
2019
entrez:
29
12
2019
pubmed:
29
12
2019
medline:
18
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31882973
doi: 10.1038/s41598-019-56618-1
pii: 10.1038/s41598-019-56618-1
pmc: PMC6934450
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20158Références
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