A stochastic model for the formation of spatial methylation patterns

DOI10.1007/978-3-319-67471-1_10MaRDI QIDQ5227327zbMATH OpenOpenAlexFDO

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

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

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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• Bayesian inference supports a location and neighbour-dependent model of DNA methylation propagation at the MGMT gene promoter in lung tumours
• Modeling dependence in methylation patterns with application to ovarian carcinomas
• A dynamic multi-compartmental model of DNA methylation with demonstrable predictive value in hematological malignancies
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• Model-based whole-genome analysis of DNA methylation fidelity
• Physical modeling of the spreading of epigenetic modifications through transient DNA looping
• Exponential dynamics of DNA methylation with age
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• Statistical inference of transmission fidelity of DNA methylation patterns over somatic cell divisions in mammals

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