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PLoS One. 2014 Jan 27;9(1):e86643. doi: 10.1371/journal.pone.0086643. eCollection 2014.

Transcriptomic meta-analysis of multiple sclerosis and its experimental models.

Author information

1
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
2
Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH&Co KG, Biberach (Riß), Germany.

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.

PMID:
24475162
PMCID:
PMC3903571
DOI:
10.1371/journal.pone.0086643
[Indexed for MEDLINE]
Free PMC Article

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