A stochastic model for the formation of spatial methylation patterns

DOI10.1007/978-3-319-67471-1_10MaRDI QIDQ5227327zbMATHOpenAlexFDO

Authors Alexander Lück, Pascal Giehr, Jörn Walter, Verena Wolf

Publication date 25 July 2019

Published in Computational Methods in Systems Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1706.10145

zbMATH Keywords

DNA methylationhidden Markov modelspatial stochastic model

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Applications of stochastic analysis (to PDEs, etc.) (60H30)

Abstract: DNA methylation is an epigenetic mechanism whose important role in development has been widely recognized. This epigenetic modification results in heritable changes in gene expression not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood and recently different mechanistic models of enzyme activities responsible for DNA methylation have been proposed. Here we extend existing Hidden Markov Models (HMMs) for DNA methylation by describing the occurrence of spatial methylation patterns over time and propose several models with different neighborhood dependencies. We perform numerical analysis of the HMMs applied to bisulfite sequencing measurements and accurately predict wild-type data. In addition, we find evidence that the enzymes' activities depend on the left 5' neighborhood but not on the right 3' neighborhood.

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• Cell type-dependent, infection-induced, aberrant DNA methylation in gastric cancer
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• A mathematical model for enhancer activation kinetics during cell differentiation
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