Detecting pathway biomarkers of diabetic progression with differential entropy

Gene expression profiling techniques measure the transcriptional dynamics of thousands of genes in parallel manners. The available high-throughput transcriptomic datasets provide unprecedented opportunities of detecting biomarkers or signatures of complex diseases such as diabetes. In this work, we propose a computational method based on differential entropy to identify diabetic pathway biomarkers in rats from gene expression profiling data. We first collect the knowledgebase-documented pathways and map them with the corresponding gene expressions in control and disease samples, respectively. The pathway entropies are defined to evaluate their dysfunction-related activities and implications during the development and progression of type 2 diabetes. We rank these pathways via their differential status of entropy dynamics in the time series. The pathway biomarkers are then screened out by their classification ability of distinguishing diabetes from controls. The comparative studies with the other alternative methods demonstrate the effectiveness and advantage of our proposed strategy of biomarker identification. The classification performances on independent datasets further validate the diagnosis applicability of these identified pathway biomarkers. The functional enrichment analyses of these pathway biomarkers also indicate the pathogenesis of diabetes.