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

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.