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Global Map of Physical Interactions among Differentially Expressed Genes in Multiple Sclerosis Relapses and Remissions.
MedLine Citation:
PMID:  21676896     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple Sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell mediated disease with a relapsing-remitting course in the majority of patients. In this study we performed a high resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large scale measurements of gene expression in Peripheral Blood Mononuclear Cells (PBMC) of MS patients in relapse or remission and healthy subjects, with large scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse vs. remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies we found that the pathways related to Regulation of Cell Death, Chemotaxis, and Inflammatory response are differentially expressed in the disease in comparison to healthy subjects, whilst pathways related to Cell adhesion, Cell migration, and Cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients vs. healthy subjects, and the epidermal growth factor receptor EGFR is a 'network-hub' in the case of MS patients with relapse vs. remission. The statistical approaches employed in this study enabled us to report new sets of genes that according to their gene expression and physical interactions are predicted to be differentially expressed in MS vs. healthy subjects, and in MS patients in relapse vs. remission. Some of these genes may be useful biomarkers for diagnosing MS and predicting relapses in MS patients.
Authors:
Tamir Tuller; Shimshi Atar; Eytan Ruppin; Michael Gurevich; Anat Achiron
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-15
Journal Detail:
Title:  Human molecular genetics     Volume:  -     ISSN:  1460-2083     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
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