title: Identifying key genes associated with Hirschsprung's disease based on bioinformatics analysis of RNA-sequencing data.
abstract: BACKGROUND
  Hirschsprung's disease (HSCR) is a type of megacolon induced by deficiency or dysfunction of ganglion cells in the distal intestine and is associated with developmental disorders of the enteric nervous system. To explore the mechanisms of HSCR, we analyzed the RNA-sequencing data of the expansion and the narrow segments of colon tissues separated from children with HSCR.
  
  
  METHODS
  RNA-sequencing of the expansion segments and the narrow segments of colon tissues isolated from children with HSCR was performed. After differentially expressed genes (DEGs) were identified using the edgeR package in R, functional and pathway enrichment analyses of DEGs were carried out using DAVID software. To further screen the key genes, protein-protein interaction (PPI) network and module analyses were conducted separately using Cytoscape software.
  
  
  RESULTS
  A total of 117 DEGs were identified in the expansion segment samples, including 47 up-regulated and 70 down-regulated genes. Functional enrichment analysis suggested that FOS and DUSP1 were implicated in response to endogenous stimulus. In the PPI network analysis, FOS (degree=20), EGR1 (degree=16), ATF3 (degree=9), NOS1 (degree=8), CCL5 (degree=8), DUSP1 (degree=7), CXCL3 (degree=6), VIP (degree=6), FOSB (degree=5), and NOS2 (degree=4) had higher degrees, which could interact with other genes. In addition, two significant modules (module 1 and module 2) were identified from the PPI network.
  
  
  CONCLUSIONS
  Several genes (including FOS, EGR1, ATF3, NOS1, CCL5, DUSP1, CXCL3, VIP, FOSB, and NOS2) might be involved in the development of HSCR through their effect on the nervous system.
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Wei-Kang
authors.initials: WK
authors.lastname: Pan
authors.affiliation: Department of Endoscopy, Shaanxi Nuclear Industry 215 Hospital, Xianyang, 712000, China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China. ygao@mail.xjtu.edu.cn.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Bai-Jun
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
mesh_terms: D002648:Child; D002681:China; D019295:Computational Biology / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D060066:Protein Interaction Maps; D017423:Sequence Analysis, RNA
keywords: Hirschsprung’s disease; differentially expressed genes; functional and pathway enrichment analysis; protein-protein interaction network