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Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array

McEwen, Lisa M, Jones, Meaghan J, Lin, David Tse Shen, Edgar, Rachel D, Husquin, Lucas T, MacIsaac, Julia L, Ramadori, Katia E, Morin, Alexander M, Rider, Christopher F, Carlsten, Chris, Quintana-Murci, Lluís, Horvath, Steve, Kobor, Michael S·2018·Clinical Epigenetics
DOI 10.1186/s13148-018-0556-2PMC PMC6192219
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Fig. 1 DNA methylation age comparison between 450K or EPIC Monocyte data across preprocessing methods. Identical samples were assayed on both the 450K and EPIC arrays, and then each preprocessed in one of four ways prior to calculating DNA methylation (DNAm) age: raw unprocessed, GenomeStudio color correction/background subtraction (GS), normal exponential out-of-band (noob) normalization, or quantile normalization. Solid colored line represents corresponding group regression line. For each regression, the Pearson’s correlation coefficient, error (median absolute error between EPIC DNAm age and 450K DNAm age), R2 value, and p value corresponding to the correlation coefficient are shown
Fig. 1 DNA methylation age comparison between 450K or EPIC Monocyte data across preprocessing methods. Identical samples were assayed on both the 450K and EPIC arrays, and then each preprocessed in one of four ways prior to calculating DNA methylation (DNAm) age: raw unprocessed, GenomeStudio color correction/background subtraction (GS), normal exponential out-of-band (noob) normalization, or quantile normalization. Solid colored line represents corresponding group regression line. For each regression, the Pearson’s correlation coefficient, error (median absolute error between EPIC DNAm age and 450K DNAm age), R2 value, and p value corresponding to the correlation coefficient are shownCC BY · PubMed Central
Fig. 2 EPIC DNA methylation age estimated in control samples from the Diesel Exhaust III Study across three tissues. DNA methylation (DNAm) age was estimated using the EPIC 334-CpG model from GenomeStudio background-subtracted and color-channel-adjusted EPIC data. Linear regression line shown with 95% confidence intervals is shown in gray. Error is the median absolute difference between EPIC DNAm age and chronological age. Pearson’s correlation coefficients (r) and corresponding p value are shown for each tissue. BAL = bronchoalveolar lavage, PBMC = peripheral blood mononuclear cells, brush = bronchial brushing
Fig. 2 EPIC DNA methylation age estimated in control samples from the Diesel Exhaust III Study across three tissues. DNA methylation (DNAm) age was estimated using the EPIC 334-CpG model from GenomeStudio background-subtracted and color-channel-adjusted EPIC data. Linear regression line shown with 95% confidence intervals is shown in gray. Error is the median absolute difference between EPIC DNAm age and chronological age. Pearson’s correlation coefficients (r) and corresponding p value are shown for each tissue. BAL = bronchoalveolar lavage, PBMC = peripheral blood mononuclear cells, brush = bronchial brushingCC BY · PubMed Central
Fig. 3 DNA methylation age acceleration variation across preprocessing methods. a Scatter plot of EPIC DNA methylation (DNAm) age calculated from raw and data from three different preprocessing methods: quantile, GenomeStudio (GS), and normal exponential out-of-band (noob) normalization. Colored regression lines and surrounding shaded gray areas represent 95% confidence interval for each group. b Boxplot of estimated DNA methylation (DNAm) age—chronological age (acceleration difference) for each preprocessing method. c Boxplot of residuals from a linear regression (DNAm age~chronological age) across methods. The median is illustrated by horizontal line with upper and lower hinges representing the 25th and 75th percentiles, upper and lower whiskers extend no further than the inter-quartile range multiplied by 1.5. Colored data points represent individual samples for each group
Fig. 3 DNA methylation age acceleration variation across preprocessing methods. a Scatter plot of EPIC DNA methylation (DNAm) age calculated from raw and data from three different preprocessing methods: quantile, GenomeStudio (GS), and normal exponential out-of-band (noob) normalization. Colored regression lines and surrounding shaded gray areas represent 95% confidence interval for each group. b Boxplot of estimated DNA methylation (DNAm) age—chronological age (acceleration difference) for each preprocessing method. c Boxplot of residuals from a linear regression (DNAm age~chronological age) across methods. The median is illustrated by horizontal line with upper and lower hinges representing the 25th and 75th percentiles, upper and lower whiskers extend no further than the inter-quartile range multiplied by 1.5. Colored data points represent individual samples for each groupCC BY · PubMed Central
Fig. 4 Absolute difference between technical replicate pairs for each processing method. The y axis represents the absolute difference between each technical replicate pair’s DNA methylation (DNAm) age. Each processing method is represented on the x axis. The median difference is indicated by the red cross for each group. The color of data points represents one technical replicate pair for ease of interpretation across methods. Error refers to the median absolute difference between DNAm age and chronological age
Fig. 4 Absolute difference between technical replicate pairs for each processing method. The y axis represents the absolute difference between each technical replicate pair’s DNA methylation (DNAm) age. Each processing method is represented on the x axis. The median difference is indicated by the red cross for each group. The color of data points represents one technical replicate pair for ease of interpretation across methods. Error refers to the median absolute difference between DNAm age and chronological ageCC BY · PubMed Central

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Research works printed but not linked: 31

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Metadata

Authors
McEwen, L. M., Jones, M. J., Lin, D. T. S., Edgar, R. D., Husquin, L. T., MacIsaac, J. L., Ramadori, K. E., Morin, A. M., Rider, C. F., Carlsten, C., Quintana-Murci, L., Horvath, S., & Kobor, M. S.
ORCID
McEwen, Lisa M
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2018-10-16
Volume
10
Issue
1
ISSN
  • 1868-7075
  • 1868-7083
DOI
10.1186/s13148-018-0556-2
PMC
PMC6192219
Cited by
147
References
4
Language
en
Licence
Funders
  • Canadian Institutes of Health Research (F15-04283)
  • National Institute on Aging (U34AG051425-0)
  • BC Lung Association, MITACS and the Michael Smith Foundation for Health Research
  • Canada Research Chairs (CA) in Occupational and Environmental Lung Disease
  • Canada Research Chairs (CA) in Social Epigenetics
  • Senior Fellow of the Canadian Institute for Advanced Research
  • Sunny Hill BC Leadership Chair in Child Development
  • European Research Council (281297)

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