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

Chavez, L., Jozefczuk, J., Grimm, C., Dietrich, J., Timmermann, B., Lehrach, H., et al. (2010). Computational analysis of genome-wide DNA methylation during the differentiation of human embryonic stem cells along the endodermal lineage. Genome Research, 20, 1441-1450. doi:10.1101/gr.110114.110.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A79-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A7A-0
Genre: Journal Article
Alternative Title : Genome Res

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 Creators:
Chavez, L.1, Author              
Jozefczuk, J.2, Author              
Grimm, C.3, Author              
Dietrich, J.4, Author
Timmermann, B.5, Author              
Lehrach, H.1, Author              
Herwig, R.4, Author
Adjaye, J.2, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433550              
2Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1479654              
3In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1479653              
4Max Planck Society, escidoc:persistent13              
5Sequencing, Max Planck Institute for Molecular Genetics, Max Planck Society, escidoc:1433559              

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 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.

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 Dates: 2010-08-27
 Publication Status: Published in print
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 Identifiers: eDoc: 547657
DOI: 10.1101/gr.110114.110
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Title: Genome Research
  Alternative Title : Genome Res
Source Genre: Journal
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Pages: - Volume / Issue: 20 Sequence Number: - Start / End Page: 1441 - 1450 Identifier: ISSN: 1549-5469 (Electronic)