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首页> 外文期刊>BMC Medical Genomics >Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice
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Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice

机译：使用microRNA靶mRNA网络和PPI网络对组学数据进行的综合分析揭示了Ews / Ewsr1 KO小鼠脊髓中Gnai1功能的调节

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Background Multifunctional transcription factor (TF) gene EWS/EWSR1 is involved in various cellular processes such as transcription regulation, noncoding RNA regulation, splicing regulation, genotoxic stress response, and cancer generation. Role of a TF gene can be effectively studied by measuring genome-wide gene expression, i.e., transcriptome, in an animal model of Ews/Ewsr1 knockout (KO). However, when a TF gene has complex multi-functions, conventional approaches such as differentially expressed genes (DEGs) analysis are not successful to characterize the role of the EWS gene. In this regard, network-based analyses that consider associations among genes are the most promising approach. Methods Networks are constructed and used to show associations among biological entities at various levels, thus different networks represent association at different levels. Taken together, in this paper, we report contributions on both computational and biological sides. Results Contribution on the computational side is to develop a novel computational framework that combines miRNA-gene network and protein-protein interaction network information to characterize the multifunctional role of EWS gene. On the biological side, we report that EWS regulates G-protein, Gnai1 , in the spinal cord of Ews/Ewsr1 KO mice using the two biological network integrated analysis method. Neighbor proteins of Gnai1 , G-protein complex subunits Gnb1, Gnb2 and Gnb4 were also down-regulated at their gene expression level. Interestingly, up-regulated genes, such as Rgs1 and Rgs19 , are linked to the inhibition of Gnai1 activities. We further verified the altered expression of Gnai1 by qRT-PCR in Ews/Ewsr1 KO mice. Conclusions Our integrated analysis of miRNA-transcriptome network and PPI network combined with qRT-PCR verifies that Gnai1 function is impaired in the spinal cord of Ews/Ewsr1 KO mice.
机译：背景技术多功能转录因子（TF）基因EWS / EWSR1参与各种细胞过程，例如转录调控，非编码RNA调控，剪接调控，遗传毒性应激反应和癌症的产生。在Ews / Ewsr1基因敲除（KO）动物模型中，可以通过测量全基因组基因表达（即转录组）来有效地研究TF基因的作用。但是，当TF基因具有复杂的多功能功能时，常规方法（例如差异表达基因（DEG）分析）无法成功表征EWS基因的作用。在这方面，考虑基因之间关联的基于网络的分析是最有前途的方法。方法网络被构建并用于显示各个层次上生物实体之间的关联，因此不同的网络代表了不同层次上的关联。两者合计，在本文中，我们报告了在计算和生物学两方面的贡献。结果计算方面的贡献是开发一种新颖的计算框架，该框架结合了miRNA基因网络和蛋白质-蛋白质相互作用网络信息来表征EWS基因的多功能作用。在生物学方面，我们报道了EWS使用两种生物网络集成分析方法调节Ews / Ewsr1 KO小鼠脊髓中的G蛋白Gnai1。 Gnai1，G蛋白复合物亚基Gnb1，Gnb2和Gnb4的相邻蛋白在其基因表达水平也被下调。有趣的是，Rgs1和Rgs19等上调基因与抑制Gnai1活性有关。我们进一步通过qRT-PCR在Ews / Ewsr1 KO小鼠中验证了Gnai1的表达改变。结论我们对miRNA转录组网络和PPI网络的综合分析与qRT-PCR相结合，证实Ews / Ewsr1 KO小鼠脊髓中的Gnai1功能受损。

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