Abstract
Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement.Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region.
Highlights
In order for a cell to function at the most basic level, its DNA encodes a core set of essential genes used to replicate, express and repair itself
The DNA methylation β value represents the absolute measurement for a given sample, and the distribution plot seems trimodal with a high peak of hypo-methylation and a low peak of hyper-methylation
The global distribution of β values is consistent with the three reference categories [38] of the unmethylated standard showing low β values and having a large proportion of CpG sites characterized by low methylation, the hemi-methylated standard showing an intermediate www.impactjournals.com/oncotarget β value and having a certain proportion of CpG sites in between the two peaks with moderate levels of methylation and the methylated standard having high β values and a smaller proportion of CpG sites characterized by high methylation
Summary
In order for a cell to function at the most basic level, its DNA encodes a core set of essential genes used to replicate, express and repair itself. These constitutive (“always on”) house-keeping genes are responsible for controlling central metabolism. Some core principles www.impactjournals.com/oncotarget of gene regulation are preserved across all cellular organisms, albeit gene regulation processes are by far more complicated in eukaryotes compared to prokaryotes. In multi-cellular systems such as humans, cellular differentiation is determined by expression of different sets of genes allowing the incremental development of a diverse set of complex tissues and organs. A cancer cell acts differently from a normal cell for the same reason, i.e. the abnormal gene expression pattern
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