title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-747, Republic of Korea.
authors.forename: Chai-Jin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Computer Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
authors.forename: Hongryul
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
authors.forename: Sean Bong
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Genome Medicine Institute and Department of Biochemistry, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Samsung Genome Institute, Samsung Medical Center and Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 135-710, Republic of Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Genome Medicine Institute and Department of Biochemistry, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: VA Boston Healthcare System, Boston, MA, 02130, USA.|Boston University Alzheimer's Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Junghee
authors.initials: J
authors.lastname: Lee
authors.affiliation: VA Boston Healthcare System, Boston, MA, 02130, USA. hoonryu@bu.edu.|Boston University Alzheimer's Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA. hoonryu@bu.edu.|Center for Neuromedicine, Brain Science Institute, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea. hoonryu@bu.edu.
authors.forename: Hoon
authors.initials: H
authors.lastname: Ryu
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-747, Republic of Korea. sunkim.bioinfo@snu.ac.kr.|Department of Computer Science and Engineering, Seoul National University, Seoul, 151-744, Republic of Korea. sunkim.bioinfo@snu.ac.kr.|Bioinformatics Institute, Seoul National University, Seoul, 151-747, Republic of Korea. sunkim.bioinfo@snu.ac.kr.
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D019295:Computational Biology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D017423:Sequence Analysis, RNA; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D002148:Calmodulin-Binding Proteins; C000605150:Ewsr1 protein, mouse; C579276:Gnai1 protein, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: EWS; Ewsr1; Gnai1; MMIA; Network analysis; PPI