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. 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, and Boolean simulations identified paths within and among all layers. The path more commonly found from the boolean simulations connects MP2K, with Th17 cells, the retinal nerve fiber layer (RNFL) thickness and the age related MS severity score (ARMSS). Combinations of several proteins (HSPB1, MP2K1, SR6, KS6B1, SRC, MK03, LCK and STAT6)) and immune cells (Th17, Th1 non-classic, CD8, CD8 Treg, CD56 neg, and B memory) were part of the paths explaining the clinical phenotype. Specific paths identified were subsequently analyzed by flow cytometry at the single-cell level.

Multiscale networks in multiple sclerosis