Fig. 1

Derivation and biomarker evaluation of a hypomethylated DNA signature from whole genome bisulfite sequencing (WGBS) of human motor neurons. MN-specific DNA hypomethylation was used to assess the proportion of MN DNA within cfDNA in plasma from ALS patients (n = 12) and CSF from controls (n = 4). We sort to verify the validity of MN-specific DNA hypomethylated regions by linking regions to target genes and cross-checking those genes with independent observations of MN gene expression; we hypothesised that correctly identified hypomethylated regions should indicate regions of open, active and transcribed chromatin which should be statistically enriched in measures of MN-specific gene expression. We linked regions to target genes using the activity-by-contact (ABC) model [15]