Network-based Analysis of Differentially Expressed Genes in Cerebrospinal Fluid (CSF) and Blood Reveals New Candidate Genes for Multiple Sclerosis

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2016 Dec 29

PMID 28028462

Citations 36

Authors

Nahid Safari-Alighiarloo

Mostafa Rezaei-Tavirani

Mohammad Taghizadeh

Seyyed Mohammad Tabatabaei

Saeed Namaki

Affiliations

Soon will be listed here.

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 (MS control) and PBMCs (relapse 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 (relapse remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways.

Discussion: 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.

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