Send to:

Choose Destination

Links from GEO DataSets

See comment in PubMed Commons below
Nucleic Acids Res. 2013 Aug;41(14):6816-27. doi: 10.1093/nar/gkt482. Epub 2013 Jun 7.

Discovering high-resolution patterns of differential DNA methylation that correlate with gene expression changes.

Author information

  • 1Center for Pharmacogenomics, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8220, St. Louis, MO 63110, USA.


Methylation of the CpG-rich region (CpG island) overlapping a gene's promoter is a generally accepted mechanism for silencing expression. While recent technological advances have enabled measurement of DNA methylation and expression changes genome-wide, only modest correlations between differential methylation at gene promoters and expression have been found. We hypothesize that stronger associations are not observed because existing analysis methods oversimplify their representation of the data and do not capture the diversity of existing methylation patterns. Recently, other patterns such as CpG island shore methylation and long partially hypomethylated domains have also been linked with gene silencing. Here, we detail a new approach for discovering differential methylation patterns associated with expression change using genome-wide high-resolution methylation data: we represent differential methylation as an interpolated curve, or signature, and then identify groups of genes with similarly shaped signatures and corresponding expression changes. Our technique uncovers a diverse set of patterns that are conserved across embryonic stem cell and cancer data sets. Overall, we find strong associations between these methylation patterns and expression. We further show that an extension of our method also outperforms other approaches by generating a longer list of genes with higher quality associations between differential methylation and expression.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

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