RNA-Seq data analysis identifies the comprehensive profile of in vivo interferon-β-stimulated genes in multiple sclerosis

2016 
Objectives Interferon-beta (IFNβ) is the most widely used drug for reducing the disease activity of multiple sclerosis (MS), although a considerable population of MS patients are refractory to IFNβ. To establish personalized therapy for MS, the molecular mechanism underlying the therapeutic effects of IFNβ in MS should be thoroughly characterized by aid of next-generation sequencing technology. Methods To elucidate a comprehensive profile of in vivo IFNβ-stimulated genes (ISGs) in MS patients, we analyzed a RNA sequencing (RNA-Seq) dataset numbered SRP045500, composed of the genome-wide transcriptome of whole blood and purified populations of CD4+ T cells, B cells, and monocytes isolated from MS patients at the time-point before and 24 h after the first treatment with IFNβ1a. Results We identified a set of 914 in vivo ISGs, containing a number of non-coding RNAs and pseudogenes, along with differential spliced genes in the whole blood of MS patients. The set of 914 ISGs were relevant to the molecular pathways defined as “interferon signaling” and “proteasome,” and were closely associated with gene ontology terms of antiviral and immune responses. We also identified 640, 653 and 1018 ISGs from CD4+ T cells, B cells, and monocytes of MS patients receiving IFNβ treatment, respectively, and extracted 95 genes shared among the three cell types as the core set of ISGs. They included 78 genes that might serve as the most consistent blood biomarkers for assessment of the immediate early in vivo response to IFNβ treatment in MS. Conclusions RNA-Seq data analysis promotes us to characterize the comprehensive profile of in vivo ISGs in MS patients receiving IFNβ treatment.
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