Fusion of expression values and protein interaction information using multi-objective optimization for improving gene clustering

Abstract

One of the crucial problems in the field of functional genomics is to identify a set of genes which are responsible for a particular cellular mechanism. The current work explores the usage of a multi-objective optimization based genetic clustering technique to classify genes into groups with respect to their functional similarities and biological relevance. Our contribution is two-fold: firstly a new quality measure to compute the goodness of gene-clusters namely protein-protein interaction confidence score is developed. This utilizes the confidence scores of the protein-protein interaction networks to measure the similarity between genes of a particular cluster with respect to their biochemical protein products. Secondly, a multi-objective based clustering approach is developed which intelligently uses integrated information of expression values of microarray dataset and protein-protein interaction confidence scores to select both statistically and biologically relevant genes. For that very purpose, some biological cluster validity indices, viz. biological homogeneity index and protein-protein interaction confidence score, along with two traditional internal cluster validity indices, viz. fuzzy partition coefficient and Pakhira-Bandyopadhyay-Maulik-index, are simultaneously optimized during the clustering process. Experimental results on three real-life gene expression datasets show that the addition of new objective capturing protein-protein interaction information aids in clustering the genes as compared to the existing techniques. The observations are further supported by biological and statistical significance tests.