Transcriptomic Meta-analysis of Multiple Sclerosis and Its Experimental Models

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 30

PMID 24475162

Citations 21

Authors

Barbara B R Raddatz

Florian Hansmann

Ingo Spitzbarth

Arno Kalkuhl

Ulrich Deschl

Wolfgang Baumgartner

Reiner Ulrich

Affiliations

Soon will be listed here.

Abstract

Background: Multiple microarray analyses of multiple sclerosis (MS) and its experimental models have been published in the last years.

Objective: Meta-analyses integrate the information from multiple studies and are suggested to be a powerful approach in detecting highly relevant and commonly affected pathways.

Data Sources: ArrayExpress, Gene Expression Omnibus and PubMed databases were screened for microarray gene expression profiling studies of MS and its experimental animal models.

Study Eligibility Criteria: Studies comparing central nervous system (CNS) samples of diseased versus healthy individuals with n >1 per group and publically available raw data were selected.

Material And Methods: Included conditions for re-analysis of differentially expressed genes (DEGs) were MS, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in rats, proteolipid protein-induced EAE in mice, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and a transgenic tumor necrosis factor-overexpressing mouse model (TNFtg). Since solely a single MS raw data set fulfilled the inclusion criteria, a merged list containing the DEGs from two MS-studies was additionally included. Cross-study analysis was performed employing list comparisons of DEGs and alternatively Gene Set Enrichment Analysis (GSEA).

Results: The intersection of DEGs in MS, EAE, TMEV-IDD, and TNFtg contained 12 genes related to macrophage functions. The intersection of EAE, TMEV-IDD and TNFtg comprised 40 DEGs, functionally related to positive regulation of immune response. Over and above, GSEA identified substantially more differentially regulated pathways including coagulation and JAK/STAT-signaling.

Conclusion: A meta-analysis based on a simple comparison of DEGs is over-conservative. In contrast, the more experimental GSEA approach identified both, a priori anticipated as well as promising new candidate pathways.

Citing Articles

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Revisiting the Pathoetiology of Multiple Sclerosis: Has the Tail Been Wagging the Mouse?.

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Delayed Astrogliosis Associated with Reduced M1 Microglia Activation in Matrix Metalloproteinase 12 Knockout Mice during Theiler's Murine Encephalomyelitis.

Hansmann F, Zhang N, Herder V, Leitzen E, Baumgartner W Int J Mol Sci. 2019; 20(7).

PMID: 30959793 PMC: 6480673. DOI: 10.3390/ijms20071702.

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