title: An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury.
abstract: BACKGROUND
  The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets.
  
  
  RESULTS
  In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery.
  
  
  CONCLUSIONS
  This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs.
authors: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave, St, Louis, MO 63110, USA.
authors: Li-Wei
authors: LW
authors: Chang
authors: Andreu
authors: A
authors: Viader
authors: Nobish
authors: N
authors: Varghese
authors: Jacqueline E
authors: JE
authors: Payton
authors: Jeffrey
authors: J
authors: Milbrandt
authors: Rakesh
authors: R
authors: Nagarajan
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods*; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D023281:Genomics; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009186:Myelin Sheath / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051767:Early Growth Response Protein 2; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors
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