title: Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis.
abstract: BACKGROUND
  The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein-protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease.
  
  
  METHODS
  Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MSvs.control) and PBMCs (relapsevs.remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression.
  
  
  RESULTS
  The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapsevs.remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MSvs.control) and CDC37, MAP3K3, MYC genes in PBMCs (relapsevs.remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways.
  
  
  CONCLUSIONS
  This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets.
authors.affiliation: Proteomics Research Center, Department of Basic Science, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Safari-Alighiarloo
authors.affiliation: Proteomics Research Center, Department of Basic Science, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Rezaei-Tavirani
authors.affiliation: Bioinformatics Department, Institute of Biochemistry and Biophysics, Tehran University , Tehran , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghizadeh
authors.affiliation: Medical Informatics Department, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Seyyed Mohammad
authors.initials: SM
authors.lastname: Tabatabaei
authors.affiliation: Immunology Department, Faculty of Medical Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Namaki
keywords: Clique analysis; Modularity; Multiple sclerosis; Protein–protein interaction network (PPIN); Topology; Transcriptome