Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms.
MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of multiple sclerosis (MS), an inflammatory disorder of the central nervous system. Here, we propose a new consensus-based strategy to analyse and integrate miRNA and gene expression data in MS as well as other publically available data to gain a deeper understanding of the role of miRNAs in MS and to overcome the challenges posed by studies with limited patient sample sizes. We processed and analysed microarray datasets, and compared the expression of genes and miRNAs in the blood of MS patients and controls. We then used our consensus and integration approach to construct two molecular networks dysregulated in MS: a miRNA- and a gene-based network. We identified 18 differentially expressed (DE) miRNAs and 128 DE genes that may contribute to the regulatory alterations behind MS. The miRNAs were linked to immunological and neurological pathways, and we exposed let-7b-5p and miR-345-5p as promising blood-derived disease biomarkers in MS. The results suggest that DE miRNAs are more informative than DE genes in uncovering pathways potentially involved in MS. Our findings provide novel insights into the regulatory mechanisms and networks underlying MS.
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.|Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
Sherry
S
Freiesleben
Department of Neurology, Division of Neuroimmunology, University of Rostock, Rostock, Germany.
Michael
M
Hecker
Department of Neurology, Division of Neuroimmunology, University of Rostock, Rostock, Germany.
Uwe Klaus
UK
Zettl
Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.|Interdisciplinary Faculty, University of Rostock, Rostock, Germany.
Georg
G
Fuellen
Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.|Division of Bioinformatics, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Leila
L
Taher
D015415:Biomarkers / Q000097:blood; D030561:Databases, Nucleic Acid; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009103:Multiple Sclerosis / Q000097:blood*
D015415:Biomarkers; C561417:MIRN345 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
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