H Liu1, X Han2, Y Li3. 1. Department of Cardiology, Binzhou People's Hospital, No. 515 Huanghe Qi Road, 256610, Binzhou, Shandong Province, China. liuhaitaobinzhou@sina.com. 2. Out-patient Department, Binzhou People's Hospital, 256610, Binzhou, Shandong Province, China. 3. Department of Orthopedic Surgery, Binzhou People's Hospital, 256610, Binzhou, Shandong Province, China.
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.
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.
Entities:
Keywords:
Diabetes mellitus, type 2; Gene expression; Heart failure; Protein interaction networks; Signaling pathways
Authors: M Mutunga; B Fulton; R Bullock; A Batchelor; A Gascoigne; J I Gillespie; S V Baudouin Journal: Am J Respir Crit Care Med Date: 2001-01 Impact factor: 21.405
Authors: P H Stone; J E Muller; T Hartwell; B J York; J D Rutherford; C B Parker; Z G Turi; H W Strauss; J T Willerson; T Robertson Journal: J Am Coll Cardiol Date: 1989-07 Impact factor: 24.094