Modular analysis of bioinformatics demonstrates a critical role for NF-kappa B in macrophage activation
Modular analysis of bioinformatics demonstrates a critical role for NF-kappa B in macrophage activation
复制标题
生物信息学的模块化分析证明 NF-kappa B 在巨噬细胞激活中的关键作用
DOI：
10.1007/s10753-014-9851-z
复制
发表时间：
2014
期刊：
影响因子：
5.1
通讯作者：
Xue Dongbo
中科院分区：
文献类型：
--
作者：
Zhang Yingmei;Wang Yingmei;Lu Ming;Qiao Xin;Sun Bei;Zhang Weihui;Xue Dongbo
为了实现鉴定调节巨噬细胞活化的基因组的目标，从基因表达综合数据库（GEO）中的三个系列（GSE 5099 -1、GSE 5099 -2和GSE 18686）的交叉点处发现总共925个活化的巨噬细胞的差异表达基因，并且基于蛋白质-蛋白质相互作用（PPI）网络构建子网络。使用CNORTH软件从子网络中识别出四个社区（K= 3）。根据热图，将群落1确定为感兴趣的基因组。GO-BP和KEGG富集分析表明，群落1中14个基因的功能主要与NF-κB通路有关。使用Cytoscape软件构建网络。该图显示STAT 1、NFKBIA、NFKAIB、JUN和RELA是调节巨噬细胞活化的关键基因。其中，RELA（NF-κB P65）是NF-κB家族的重要成员，NF-κ BIA（IκBα）和NF-κ AI B（IκBβ）是NF-κB的抑制因子。通过CMap软件鉴定了能够调节这五个基因的小分子，并使用Cytoscape软件生成网络图，为开发调节巨噬细胞活化的新药提供参考。
To achieve the goal of identifying the gene groups that regulated macrophage activation, a total of 925 differentially expressed genes of activated macrophages were found at the intersection of the three series (GSE5099-1, GSE5099-2, and GSE18686) from the Gene Expression Omnibus (GEO) database, and a sub-network was constructed based on the protein-protein interaction (PPI) network. Four communities (K= 3) were identified from the sub-network using the CFinder software. Community 1 was considered as the gene group of interest base on the heat map. GO-BP and KEGG enrichment analysis with the DAVID software showed that the functions of the 14 genes in community 1 were mainly related to the NF-κB pathway. A network was constructed using the Cytoscape software. The diagram showed that STAT1, NFKBIA, NFKAIB, JUN, and RELA were the key genes in the regulation of macrophage activation. Among these genes, RELA (NF-κB P65) was an important member of the NF-κB family, while NFKBIA (IκBα) and NFKAIB (IκBβ) were the inhibitory factors of NF-κB. Small molecules capable of regulating these five genes were identified via the CMap software, and a network diagram was generated using the Cytoscape software to provide a reference for the development of new drugs that regulate macrophage activation.