Fig. 1

Outline of the systems medicine approach to identify mechanistic drivers of different MS lesion types. Using RNAseq we analysed the transcriptome of normal-appearing white matter (NAWM), and lesion evolution/fate (active, inactive, chronic active, remyelinating) in the white matter (WM) of patients with progressive MS. We performed a comprehensive computational data analysis – from differential expression to de novo network enrichment – and examined selected molecules of interest by a combination of RNAscope, immunohistochemistry and immunofluorescence to confirm their cellular source and protein expression levels