Network expansion and pathway enrichment analysis towards biologically significant findings from microarrays

In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease), and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA) for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI) database, and pathway enrichment from the human pathway database (HPD). We use a recently-published microarray dataset (GSE24215) related to insulin resistance and type 2 diabetes (T2D) as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.