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Fig. 3 | Clinical Epigenetics

Fig. 3

From: Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis

Fig. 3

Functional association of 5mC and 5hmC changes to axonal guidance, CREB signalling and synaptic plasticity. a Top canonical pathways associated with “true” methylation (5mC) and hydroxymethylation (5hmC) between multiple sclerosis cases (MS, n = 10) and non-neurological controls (Ctr, n = 7) using Ingenuity Pathway Analysis (IPA). Results for all adjusted P value < 0.05 5mC-DMPs +5hmC-DhMPs (black) as well as 5mC-DMPs (purple) and 5hmC-DhMPs (orange) separately. Significance is represented as − log10(B-H, P value) after adjustment using Benjamini-Hochberg (B-H) correction. b Multidimensional scaling of over-represented biological function terms associated with 5mC-DMPs (purple) and 5hmC-DhMPs (orange) (adjusted P value < 0.05), separately, between MS cases (n = 10) and Ctr (n = 7), according to semantic similarities, using REVIGO. The circle size represents − log10(B-H, P value) after adjustment using Benjamini-Hochberg (B-H) correction. c Representation of the genes from axonal guidance network using STRING analysis. Grey gradient indicates the strength of data support (darker grey representing stronger evidence) and colours represent different cluster (kmeans clustering set at 5). d Plots illustrating genes associated with top 5mC-DMR and 5hmC-DhMR (left and middle panel) or with BS-DMRs and 5hmC-DhMRs (right panel) (|Δβ| > 0.05). e Plots illustrating genes associated with top 5mC-DMR, 5hmC-DhMR or BS-DMRs (Δβ > 0.05). The hg19 ideogram illustrating chromosome and cytoband information, the complete gene structure of the locus (blue track), CpG Island (CGI) feature (green track), probes and DMR (black) location are shown. Methylation (β-values) of single CpGs within and outside the DMR for individual cases and controls is depicted in red and blue, respectively, with connecting lines indicating mean methylation for each consecutive CpG

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