Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genome Res. 2008 Oct;18(10):1652-9. doi: 10.1101/gr.080721.108. Epub 2008 Sep 2.

MEDME: an experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment.

Author information

  • 1Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Abstract

DNA methylation is an important component of epigenetic modifications that influences the transcriptional machinery and is aberrant in many human diseases. Several methods have been developed to map DNA methylation for either limited regions or genome-wide. In particular, antibodies specific for methylated CpG have been successfully applied in genome-wide studies. However, despite the relevance of the obtained results, the interpretation of antibody enrichment is not trivial. Of greatest importance, the coupling of antibody-enriched methylated fragments with microarrays generates DNA methylation estimates that are not linearly related to the true methylation level. Here, we present an experimental and analytical methodology, MEDME (modeling experimental data with MeDIP enrichment), to obtain enhanced estimates that better describe the true values of DNA methylation level throughout the genome. We propose an experimental scenario for evaluating the true relationship in a high-throughput setting and a model-based analysis to predict the absolute and relative DNA methylation levels. We successfully applied this model to evaluate DNA methylation status of normal human melanocytes compared to a melanoma cell strain. Despite the low resolution typical of methods based on immunoprecipitation, we show that model-derived estimates of DNA methylation provide relatively high correlation with measured absolute and relative levels, as validated by bisulfite genomic DNA sequencing. Importantly, the model-derived DNA methylation estimates simplify the interpretation of the results both at single-loci and at chromosome-wide levels.

PMID:
18765822
[PubMed - indexed for MEDLINE]
PMCID:
PMC2556264
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk