title: 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.
  
  
  CONCLUSIONS
  The identified disrupted pathways - focal adhesion, VEGF signaling, and MAPK signaling - might play important roles in the progression of T2DM heart failure.
authors.affiliation: Department of Cardiology, Binzhou People's Hospital, No. 515 Huanghe Qi Road, 256610, Binzhou, Shandong Province, China. liuhaitaobinzhou@sina.com.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Out-patient Department, Binzhou People's Hospital, 256610, Binzhou, Shandong Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Orthopedic Surgery, Binzhou People's Hospital, 256610, Binzhou, Shandong Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D058606:Accessory Atrioventricular Bundle; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*
chemical_list: D020543:Proteome
keywords: Diabetes mellitus, type 2; Gene expression; Heart failure; Protein interaction networks; Signaling pathways