Computational analysis of genome-wide DNA methylation during the differentiation of human embryonic stem cells along the endodermal lineage

  1. James Adjaye1,3,4,5
  1. 1 Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, D-14195 Berlin, Germany;
  2. 2 Next Generation Sequencing Group, Max-Planck-Institute for Molecular Genetics, D-14195 Berlin, Germany;
  3. 3 The Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia

    1. ↵4 These authors contributed equally to this work.

    Abstract

    The generation of genome-wide data derived from methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) has become a major tool for epigenetic studies in health and disease. The computational analysis of such data, however, still falls short on accuracy, sensitivity, and speed. We propose a time-efficient statistical method that is able to cope with the inherent complexity of MeDIP-seq data with similar performance compared with existing methods. In order to demonstrate the computational approach, we have analyzed alterations in DNA methylation during the differentiation of human embryonic stem cells (hESCs) to definitive endoderm. We show improved correlation of normalized MeDIP-seq data in comparison to available whole-genome bisulfite sequencing data, and investigated the effect of differential methylation on gene expression. Furthermore, we analyzed the interplay between DNA methylation, histone modifications, and transcription factor binding and show that in contrast to de novo methylation, demethylation is mainly associated with regions of low CpG densities.

    Footnotes

    • Received May 7, 2010.
    • Accepted July 16, 2010.
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    1. Published in Advance August 27, 2010, doi: 10.1101/gr.110114.110 Genome Res. 20: 1441-1450 Copyright © 2010 by Cold Spring Harbor Laboratory Press

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