Clustering-based gene-subnetwork biomarker identification using gene expression data

The identification of predictive biomarkers of complex disease with robustness and specificity is an ongoing challenge. Gene expressions provide information on how the cell reacts to a particular state and the relationship of genes may lead to novel information. A network-based approach integrating expression data with protein-protein interaction network can be used to identify gene-subnetwork biomarkers for a particular disease. However, cancer datasets are heterogeneous in nature containing unknown or undefined subtypes of cancers. In this study, we propose a gene-subnetwork biomarker identification approach by implementing an Expectation-Maximization (EM) clustering technique to homogenize the dataset. To validate our proposed method. Lung cancer expression datasets are used to identify gene-subnetwork biomarkers. The evaluation of gene-subnetwork biomarkers is done by 5-fold cross-validation on an independent dataset. The comparison between non-clustering and clustering-based gene-subnetwork identification showed that clustering produced improved classification performance at a statistically significant level. Furthermore, preliminary functional analysis results showed more significant subnetworks were identified using the proposed approach.