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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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12920-016-0195-4) contains supplementary material, which is available to authorized users.

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