Extended Data Fig. 9: MIRAS patient cerebral cortex proteome and transcriptome.

(a) Proteome profiling of MIRAS patient cerebral cortex. Volcano plot: significance (p-value) and fold change. 57 of the proteins with p-value < 0.05 (two-sample Student’s T-test) are associated with immune/antiviral pathways (highlighted in blue). N = 3 patients and 6 controls, all females. (b) Canonical pathway enrichment analysis of cerebral cortex proteome in MIRAS (as in a). Ingenuity pathways analyses on proteins significantly affected (p-value < 0.05) in MIRAS; pathway p-value (Fisher’s exact test) and ratio (number of molecules from the dataset that map to the pathway divided by the total number of molecules that map to the canonical pathway). Blue: pathways related to immune and/or viral process; orange: pathways related to mitochondrial functions. (c) Comparative pathway profiling of cerebral cortex transcriptome of patient/control (as in Fig. 5h) versus TBEV-infected/uninfected wildtype mice (as in Fig. 3f). Biological pathways (analysed using gProfiler server; Fisher’s one-tailed test with multiple testing correction using the server default algorithm g:SCS) enriched with downregulated genes (p-value < 0.05, fold change > −1.5) in patient/control or with upregulated genes (adj-p-value < 0.05, fold change>1.5) in TBEV 4 dpi/uninfected wildtype control mice. Left: Top common overlapping pathways of the two datasets (pathway adj-p-value < 0.05) are tabulated with the pathway-associated gene count. Right: the pathway-associated gene count and adj-p-value. 58 overlapping pathways between the two datasets are highlighted in green shade. Selected top pathways related to virus and immune response are annotated in blue text to depict the opposed regulation.