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Multiscale networks in multiple sclerosis

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Item Type:Article
Title:Multiscale networks in multiple sclerosis
Creators Name:Kennedy, K.E. and Kerlero de Rosbo, N. and Uccelli, A. and Cellerino, M. and Ivaldi, F. and Contini, P. and De Palma, R. and Harbo, H.F. and Berge, T. and Bos, S.D. and Høgestøl, E.A. and Brune-Ingebretsen, S. and de Rodez Benavent, S.A. and Paul, F. and Brandt, A.U. and Bäcker-Koduah, P. and Behrens, J. and Kuchling, J. and Asseyer, S. and Scheel, M. and Chien, C. and Zimmermann, H. and Motamedi, S. and Kauer-Bonin, J. and Saez-Rodriguez, J. and Rinas, M. and Alexopoulos, L.G. and Andorra, M. and Llufriu, S. and Saiz, A. and Blanco, Y. and Martinez-Heras, E. and Solana, E. and Pulido-Valdeolivas, I. and Martinez-Lapiscina, E.H. and Garcia-Ojalvo, J. and Villoslada, P.
Abstract:Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls. Multilayer networks were constructed using mutual information for topological analysis, and Boolean simulations were constructed using Pearson correlation to identified paths within and among all layers. The path more commonly found from the Boolean simulations connects protein MK03, with total T cells, the thickness of the retinal nerve fiber layer (RNFL), and the walking speed. This path contains nodes involved in protein phosphorylation, glial cell differentiation, and regulation of stress-activated MAPK cascade, among others. Specific paths identified were subsequently analyzed by flow cytometry at the single-cell level. Combinations of several proteins (GSK3AB, HSBP1 or RS6) and immune cells (Th17, Th1 non-classic, CD8, CD8 Treg, CD56 neg, and B memory) were part of the paths explaining the clinical phenotype. The advantage of the path identified from the Boolean simulations is that it connects information about these known biological pathways with the layers at higher scales (retina damage and disability). Overall, the identified paths provide a means to connect the molecular aspects of MS with the overall phenotype.
Keywords:Brain, Heat-Shock Proteins, Multiple Sclerosis, Optical Coherence Tomography, Prospective Studies, Retina
Source:PLoS Computational Biology
Publisher:Public Library of Science
Page Range:e1010980
Date:February 2024
Official Publication:https://doi.org/10.1371/journal.pcbi.1010980
PubMed:View item in PubMed

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