Liu H, Han X, Li Y
Department of Cardiology, Binzhou People's Hospital, No. 515 Huanghe Qi Road, 256610, Binzhou, Shandong Province, China.
Out-patient Department, Binzhou People's Hospital, 256610, Binzhou, Shandong Province, China.
Herz. 2017 Feb;42(1):98-106. doi: 10.1007/s00059-016-4445-1. Epub 2016 Jun 30.
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.
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.
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.
The identified disrupted pathways - focal adhesion, VEGF signaling, and MAPK signaling - might play important roles in the progression of T2DM heart failure.
本研究旨在通过系统追踪重新加权的蛋白质-蛋白质相互作用（PPI）网络中改变的模块，筛选2型糖尿病（T2DM）心力衰竭中被破坏的通路。
我们通过整合基因表达数据和PPI网络，对非T2DM和T2DM心力衰竭受试者的模块进行系统鉴定和比较。利用Spearman相关系数（SCC）构建并重新加权非T2DM心力衰竭和T2DM心力衰竭的PPI网络。随后，使用团合并算法探索PPI网络中的模块，接着基于最大权重二分匹配法鉴定被破坏的模块并按降序排序。最后，对被破坏模块中的基因进行通路富集分析，以确定T2DM心力衰竭中的生物学通路。
通过比较非T2DM心力衰竭和T2DM心力衰竭的模块，共探索出804个被破坏的模块。被破坏模块中的基因在39个类别中显著富集（p < 1.00E - 06）。其中，最显著的通路是粘着斑、血管内皮生长因子（VEGF）信号通路和丝裂原活化蛋白激酶（MAPK）信号通路。
所鉴定出的被破坏通路——粘着斑、VEGF信号通路和MAPK信号通路——可能在T2DM心力衰竭的进展中起重要作用。
