In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as DNA methylation reflect environmental risk factors, and are increasingly recognised for t
heir fundamental role in diseases such as cancer. DNA methylation is a gene-regulatory pattern, and hence provides a means by which to assess genomic regulatory interactions. Network models are a natural way to represent and analyse groups of such interactions. The utility of network models also increases as the quantity of data and number of variables increase, making them increasingly relevant to large-scale genomic studies. We propose methodology to infer prognostic genomic networks from a DNA methylation-based measure of genomic interaction and association. We then show how to identify prognostic biomarkers from such networks, which we term `network community oncomarkers. We illustrate the power of our proposed methodology in the context of a large publicly available breast cancer dataset.
We discuss the problem of proteasomal degradation of proteins. Though proteasomes are important for all aspects of the cellular metabolism, some details of the physical mechanism of the process remain unknown. We introduce a stochastic model of the p
roteasomal degradation of proteins, which accounts for the protein translocation and the topology of the positioning of cleavage centers of a proteasome from first principles. For this model we develop the mathematical description based on a master-equation and techniques for reconstruction of the cleavage specificity inherent to proteins and the proteasomal translocation rates, which are a property of the proteasome specie, from mass spectroscopy data on digestion patterns. With these properties determined, one can quantitatively predict digestion patterns for new experimental set-ups. Additionally we design an experimental set-up for a synthetic polypeptide with a periodic sequence of amino acids, which enables especially reliable determination of translocation rates.
