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


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


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


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.


CONCLUSIONS
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.
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Barbara B R
BB
Raddatz
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Florian
F
Hansmann
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Ingo
I
Spitzbarth
Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH&Co KG, Biberach (Riß), Germany.
Arno
A
Kalkuhl
Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH&Co KG, Biberach (Riß), Germany.
Ulrich
U
Deschl
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Wolfgang
W
Baumgärtner
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany ; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
Reiner
R
Ulrich
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects; D011510:Proteolipids / Q000009:adverse effects; D051381:Rats; D013045:Species Specificity; D017945:Theilovirus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D063308:Myelin-Oligodendrocyte Glycoprotein; D011510:Proteolipids; D014409:Tumor Necrosis Factor-alpha