Relational Analysis of CpG Islands Methylation and Gene Expression in Human Lymphomas Using Possibilistic C-Means Clustering and Modified Cluster Fuzzy Density

Heterogeneous genetic and epigenetic alterations are commonly found in human non-Hodgkin's lymphomas (NHL). One such epigenetic alteration is aberrant methylation of gene promoter-related CpG islands, where hypermethylation frequently results in transcriptional inactivation of target genes, while a decrease or loss of promoter methylation (hypomethylation) is frequently associated with transcriptional activation. Discovering genes with these relationships in NHL or other types of cancers could lead to a better understanding of the pathobiology of these diseases. The simultaneous analysis of promoter methylation using differential methylation hybridization (DMH) and its associated gene expression using expressed CpG island sequence tag (ECIST) microarrays generates a large volume of methylation-expression relational data. To analyze this data, we propose a set of algorithms based on fuzzy sets theory, in particular possibilistic c-means (PCM) and cluster fuzzy density. For each gene, these algorithms calculate measures of confidence of various methylation-expression relationships in each NHL subclass. Thus, these tools can be used as a means of high volume data exploration to better guide biological confirmation using independent molecular biology methods