Cluster analysis of cancer data using semantic similarity, sequence similarity and biological measures

Clustering of genes on the basis of expression profiles is generally the first step in understanding how a class of genes behaves in a biological process. A number of supervised and unsupervised algorithms are available in statistics and machine learning literature for clustering microarray data, but the algorithms are restricted in their ability to evaluate the results of a clustering algorithm in the light of biologically meaningful clusters. If two gene sequences are similar, then we would expect that their genetic expressions are similar and that they are similarly annotated in the Gene Ontology (GO) databases. Hence a comparison of the expression level similarity of two gene sequences against their corresponding similarity of annotation in the GO can establish this fact. Semantic similarity has now become a valuable tool for validating the results drawn from biomedical studies such as gene clustering and gene expression data analysis. This paper borrows from our previous work on meta-ensembles using cancer datasets where the output of several clustering algorithms are subsequently fed to a consensus building process to generate a stable set of cluster results. Next, these cluster results are further refined through a sequence of biological validation process for each gene pair of a given cluster using semantic similarity and sequence similarity. We have tested our approach on several benchmark cancer datasets in an attempt to provide a more accurate biological analysis of the clusters and the results have been found to be satisfactory.

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