Identifying disrupted pathways by tracking altered modules in type 2 DM-related heart failure

Abstract

Background: This study aimed to screen disrupted pathways in type 2 diabetes mellitus (T2DM) heart failure by systematically tracking the altered modules of reweighted protein-protein interaction (PPI) networks.

Methods: We implemented systematic identification and comparison of modules across non-T2DM and T2DM heart failure subjects by integrating gene expression data and PPI networks. The PPI networks of non-T2DM heart failure and T2DM heart failure were constructed and reweighted by means of Spearman's correlation coefficient (SCC). Subsequently, a clique-merging algorithm was used to explore the modules in the PPI network, followed by the identification of disrupted modules based on a maximum-weight bipartite matching and sorting in descending order. Finally, pathway enrichment analyses were conducted for genes in disrupted modules to determine the biological pathways in T2DM heart failure.

Results: By comparing the modules of non-T2DM heart failure and T2DM heart failure, 804 disrupted modules were explored. The genes in disrupted modules were significantly enriched in 39 categories (p < 1.00E-06). Of these, the most significant pathways were the focal adhesion, vascular endothelial growth factor (VEGF) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways.

Conclusion: The identified disrupted pathways - focal adhesion, VEGF signaling, and MAPK signaling - might play important roles in the progression of T2DM heart failure.

Keywords: Diabetes mellitus, type 2; Gene expression; Heart failure; Protein interaction networks; Signaling pathways.