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Identifying and correcting epigenetics measurements for systematic sources of variation
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2018 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 38Article in journal (Refereed) Published
Abstract [en]

Background: Methylation measures quantified by microarray techniques can be affected by systematic variation due to the technical processing of samples, which may compromise the accuracy of the measurement process and contribute to bias the estimate of the association under investigation. The quantification of the contribution of the systematic source of variation is challenging in datasets characterized by hundreds of thousands of features.In this study, we introduce a method previously developed for the analysis of metabolomics data to evaluate the performance of existing normalizing techniques to correct for unwanted variation. Illumina Infinium HumanMethylation450K was used to acquire methylation levels in over 421,000 CpG sites for 902 study participants of a case-control study on breast cancer nested within the EPIC cohort. The principal component partial R-square (PC-PR2) analysis was used to identify and quantify the variability attributable to potential systematic sources of variation. Three correcting techniques, namely ComBat, surrogate variables analysis (SVA) and a linear regression model to compute residuals were applied. The impact of each correcting method on the association between smoking status and DNA methylation levels was evaluated, and results were compared with findings from a large meta-analysis.

Results:  = 96).

Conclusions: The three correction methods removed systematic variation in DNA methylation data, as assessed by the PC-PR2, which lent itself as a useful tool to explore variability in large dimension data. SVA produced more conservative findings than ComBat in the association between smoking and DNA methylation.

Place, publisher, year, edition, pages
London: BioMed Central, 2018. Vol. 10, article id 38
Keyword [en]
Epigenetics, Methylation, Normalization, PC-PR2, Smoking status
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-146374DOI: 10.1186/s13148-018-0471-6ISI: 000428271200001PubMedID: 29588806OAI: oai:DiVA.org:umu-146374DiVA, id: diva2:1195766
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-06-09Bibliographically approved

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Harlid, Sophia

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
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  • de-DE
  • en-GB
  • en-US
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  • nn-NO
  • nn-NB
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  • Other locale
More languages
Output format
  • html
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  • asciidoc
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