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  • 1.
    Carlström, Karl E.
    et al.
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Ewing, Ewoud
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Granqvist, Mathias
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Gyllenberg, Alexandra
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Aeinehband, Shahin
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Enoksson, Sara Lind
    Department of Clinical Immunology Karolinska University Hospital, Stockholm, Sweden.
    Checa, Antonio
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Badam, Tejaswi
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Physics, Chemistry & Biology (IFM), Bioinformatics, Linköping University, Sweden.
    Huang, Jesse
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Gomez-Cabrero, David
    Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Publica de Nevarra (UPNA), IdiSNA, Pamplona, Spain.
    Gustafsson, Mika
    Department of Physics, Chemistry and Biology, Linköping University, Sweden.
    Al Nimer, Faiez
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Craig E.
    Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Kockum, Ingrid
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Olsson, Tomas
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Jagodic, Maja
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neurosciences, Section of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, p. 1-13, article id 3081Article in journal (Refereed)
    Abstract [en]

    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.

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  • 2.
    de Weerd, Hendrik A.
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Badam, Tejaswi V. S.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Martínez-Enguita, David
    Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Åkesson, Julia
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment. Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Muthas, Daniel
    Translational Science & Experimental Medicine, Early Respiratory, Inflammation and Autoimmunity, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Gustafsson, Mika
    Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Lubovac-Pilav, Zelmina
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    MODifieR: an ensemble R package for inference of disease modules from transcriptomics networks2020In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811Article in journal (Refereed)
    Abstract [en]

    MOTIVATION: Complex diseases are due to the dense interactions of many disease-associated factors that dysregulate genes that in turn form so-called disease modules, which have shown to be a powerful concept for understanding pathological mechanisms. There exist many disease module inference methods that rely on somewhat different assumptions, but there is still no gold standard or best performing method. Hence, there is a need for combining these methods to generate robust disease modules.

    RESULTS: We developed MODule IdentiFIER (MODifieR), an ensemble R package of nine disease module inference methods from transcriptomics networks. MODifieR uses standardized input and output allowing the possibility to combine individual modules generated from these methods into more robust disease-specific modules, contributing to a better understanding of complex diseases.

    AVAILABILITY: MODifieR is available under the GNU GPL license and can be freely downloaded from https://gitlab.com/Gustafsson-lab/MODifieR and as a Docker image from https://hub.docker.com/r/ddeweerd/modifier.

    SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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