Computational Analysis of Pathways Enrichment in DNA Methylation Array Data

DNA methylation is an important epigenetic mechanism that is being gradually deciphered especially after the advent of high-throughput technologies. However, the steps through which DNA methylation targets affect gene pathways remain unclear. This work presents a novel computational approach that maps DNA methylation data from Infinium HumanMethylation450 BeadChip array to gene pathways and identifies significant associations between differentially methylated loci and significantly enriched pathways. The objective is to provide a broader view of the DNA methylation mechanism by examining the extent to which certain biological pathways may be modulated by alterations of the DNA methylation profile. To test this method we used data from a patient with chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in the western world, where alterations of DNA methylation are critically implicated in disease biology. Source code is available upon request.