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Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment.

Paolo Fagone | Emanuela Mazzon | Santa Mammana | Roberto Di Marco | Flaminia Spinasanta | Maria Sofia Basile | Maria Cristina Petralia | Placido Bramanti | Ferdinando Nicoletti | Katia Mangano
Molecular medicine reports | 2019

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of autoimmune etiopathogenesis, and is characterized by various neurological symptoms. Glatiramer acetate and interferon‑β are administered as first‑line treatments for this disease. In non‑responsive patients, several second‑line therapies are available, including natalizumab; however, a percentage of MS patients does not respond, or respond partially. Therefore, it is of the utmost importance to develop a diagnostic test for the prediction of drug response in patients suffering from complex diseases, such as MS, where several therapeutic options are already available. By a machine learning approach, the UnCorrelated Shrunken Centroid algorithm was applied to identify a subset of genes of CD4+ T cells that may predict the pharmacological response of relapsing‑remitting MS patients to natalizumab, before the initiation of therapy. The results from the present study may provide a basis for the design of personalized therapeutic strategies for patients with MS.

Pubmed ID: 31180553

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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GeneMANIA (tool)

RRID:SCR_005709

Data analysis service to predict the function of your favorite genes and gene sets. Indexing 1,421 association networks containing 266,984,699 interactions mapped to 155,238 genes from 7 organisms. GeneMANIA interaction networks are available for download in plain text format. GeneMANIA finds other genes that are related to a set of input genes, using a very large set of functional association data. Association data include protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity. You can use GeneMANIA to find new members of a pathway or complex, find additional genes you may have missed in your screen or find new genes with a specific function, such as protein kinases. Your question is defined by the set of genes you input. If members of your gene list make up a protein complex, GeneMANIA will return more potential members of the protein complex. If you enter a gene list, GeneMANIA will return connections between your genes, within the selected datasets. GeneMANIA suggests annotations for genes based on Gene Ontology term enrichment of highly interacting genes with the gene of interest. GeneMANIA is also a gene recommendation system. GeneMANIA is also accessible via a Cytoscape plugin, designed for power users. Platform: Online tool, Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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LIMMA (tool)

RRID:SCR_010943

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RRID:SCR_010974

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RRID:SCR_013575

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