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Beschreibung:
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 ...