title: Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy.
abstract: OBJECTIVE
  The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data.
  
  
  METHODS
  Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy.
  
  
  RESULTS
  Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer's disease and focal adhesion.
  
  
  CONCLUSIONS
  We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy.
authors: Department of Neurology and Shandong Sleep Medical Center, Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors: Zhenhua
authors: Z
authors: Liu
authors: Department of Neurology, Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors: Jiali
authors: J
authors: Zhao
authors: Department of Neurology, Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors: Yinyin
authors: Y
authors: Tan
authors: Shandong Sleep Medical Center, Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors: Minglu
authors: M
authors: Tang
authors: Shandong Sleep Medical Center, Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors: Guanzhen
authors: G
authors: Li
keywords: Narcolepsy; disrupted pathways; dysregulated modules; protein-protein interaction network