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Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). The redox master regulator Nrf2, essential for redox balance, is a target of DMF, but its precise therapeutic mechanisms of action remain elusive. Here we show impact of DMF on circulating monocytes and T cells in a prospective longitudinal RRMS patient cohort. DMF increases the level of oxidized isoprostanes in peripheral blood. Other observed changes, including methylome and transcriptome profiles, occur in monocytes prior to T cells. Importantly, monocyte counts and monocytic ROS increase following DMF and distinguish patients with beneficial treatment-response from non-responders. A single nucleotide polymorphism in the ROS-generating NOX3 gene is associated with beneficial DMF treatment-response. Our data implicate monocyte-derived oxidative processes in autoimmune diseases and their treatment, and identify NOX3 genetic variant, monocyte counts and redox state as parameters potentially useful to inform clinical decisions on DMF therapy of RRMS.
Pubmed ID: 31300673
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Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA Java based software tool designed to simplify and expedite the process of haplotype analysis by providing a common interface to several tasks relating to such analyses. Haploview currently allows users to examine block structures, generate haplotypes in these blocks, run association tests, and save the data in a number of formats. All functionalities are highly customizable. (entry from Genetic Analysis Software) * LD & haplotype block analysis * haplotype population frequency estimation * single SNP and haplotype association tests * permutation testing for association significance * implementation of Paul de Bakker's Tagger tag SNP selection algorithm. * automatic download of phased genotype data from HapMap * visualization and plotting of PLINK whole genome association results including advanced filtering options Haploview is fully compatible with data dumps from the HapMap project and the Perlegen Genotype Browser. It can analyze thousands of SNPs (tens of thousands in command line mode) in thousands of individuals. Note: Haploview is currently on a development and support freeze. The team is currently looking at a variety of options in order to provide support for the software. Haploview is an open source project hosted by SourceForge. The source can be downloaded at the SourceForge project site.
View all literature mentionsA powerful genomic analysis platform that provides access to hundreds of tools for gene expression analysis, proteomics, SNP analysis, flow cytometry, RNA-seq analysis, and common data processing tasks. A web-based interface provides easy access to these tools and allows the creation of multi-step analysis pipelines that enable reproducible in silico research.
View all literature mentionsSoftware using a beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsSoftware R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. Used to process probe level data and for exploratory oligonucleotide array analysis.
View all literature mentionsSoftware package that includes quality control metrics, a selection of normalization methods and novel methods to identify differentially methylated regions and to highlight copy number aberrations.
View all literature mentionsWeb application to collaboratively create interactive graphs and share them with others. JavaScript toolbox plotly.js enables users with little to no web development skills to make scientific charts.
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