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Thesis - Doctoral dissertation | @PhdThesis | Doktorarbeit

Author(s)*:Bock, Christoph
BibTeX citekey*:Bock2008

Title, School
Title*:Computational Epigenetics
School:Universität des Saarlandes
Type of Thesis*:Doctoral dissertation

Publishers Name:Universität des Saarlandes
Publishers Address:Saarbrücken

Note, Abstract, Copyright
LaTeX Abstract:Epigenetic research aims to understand heritable gene regulation that is not directly encoded in the DNA sequence. Epigenetic mechanisms such as DNA methylation and histone modifications modulate the packaging of the DNA in the nucleus and thereby influence gene expression. Patterns of epigenetic information are faithfully propagated over multiple cell divisions, which makes epigenetic gene regulation a key mechanism for cellular differentiation and cell fate decisions. In addition, incomplete erasure of epigenetic information can lead to complex patterns of non-Mendelian inheritance. Stochastic and environment-induced epigenetic defects are known to play a major role in cancer and ageing, and they may also contribute to mental disorders and autoimmune diseases.

Recent technical advances – such as the development of the ChIP-on-chip and ChIP-seq protocols for genome-wide mapping of epigenetic information – have started to convert epigenetic research into a high-throughput endeavor, to which bioinformatics is expected to make significant contributions. This thesis describes computational work at the intersection of epigenetics and genome research, aiming to address the bioinformatic challenges posed by the human epigenome. While its methods are carried over and adapted from bioinformatics and related fields (including data mining, machine learning, statistics, algorithms, optimization,
software engineering and databases), its overarching goal is to contribute to epigenetic research, both directly through analyzing and modeling of epigenetic information, and indirectly through the development of practically useful methods and software toolkits. This thesis is broadly structured into four parts. The first part gives a brief introduction into epigenetic regulation and inheritance, and reviews the emerging field of computational epigenetics. The second part addresses the question of genome-epigenome interactions using machine learning methods. It is shown that accurate predictions of DNA methylation and other epigenetic modifications can be derived from the genomic DNA sequence. Based on this finding, the EpiGRAPH web service for epigenome analysis and prediction is described, and methods for refined annotation of CpG islands in the human genome are proposed. The third part is dedicated to large-scale analysis of DNA methylation, which is the best-known epigenetic phenomenon. The BiQ Analyzer software toolkit is presented, together with a bioinformatic analysis of the “National Methylome Project for Chromosome 21” dataset, for which BiQ Analyzer had played an enabling role. This part concludes with statistical modeling of DNA methylation variation and an analysis of its implications for DNA methylation mapping in a large number of human individuals. The fourth part describes two pilot projects applying
the bioinformatic concepts of this thesis to cancer epigenetics. First, genome-scale datasets are probed for evidence of a link between DNA methylation and Polycomb binding, which is believed to play a role in epigenetic deregulation of cancer cells. Second, a biomarker that tests for cancer-specific DNA methylation is optimized and validated for use in clinical settings. Arguably the most interesting result of this thesis is the unexpectedly high correlation between genome and epigenome that was found by several methods and based on multiple epigenome
datasets. This finding suggests that the role of the genome for epigenetic regulation
has been underappreciated, and it underlines the importance of integrated analysis of genome and epigenome. With the EpiGRAPH web service for (epi-) genome analysis and prediction, a research tool is provided to facilitate further investigation of this striking interaction.

Download Access Level:Internal

Referees, Status, Dates
1. Referee:Prof. Dr. Thomas Lengauer, Ph.D.
2. Referee:Prof. Dr. Jörn Walter
Date Kolloquium:2 October 2008
Chair Kolloquium:Prof. Dr. Gerhard Weikum

MPG Unit:Max-Planck-Institut für Informatik
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BibTeX Entry:
AUTHOR = {Bock, Christoph},
TITLE = {Computational Epigenetics},
PUBLISHER = {Universität des Saarlandes},
SCHOOL = {Universit{\"a}t des Saarlandes},
YEAR = {2008},
TYPE = {Doctoral dissertation}
PAGES = {148},
ADDRESS = {Saarbr{\"u}cken},
MONTH = {October},

Entry last modified by Marc Schmitt, 06/29/2011
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Marc Schmitt
06/29/2011 11:17:24 AM

Marc Schmitt

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