Of note, ~ 22.5% of the genes showed negative correlations between gene body5hmC and host-gene mRNA in normal controls but positive associations in grade 4 gliomas (i.e., re-wired 5hmC-expression features) were found to be significantly associated with pathways such as focal adhesion, tight junction and PI3K-Akt signaling pathway (hypergeometric test p < 0.01 and gene count ≥ 10) (Fig. 2F–G). This evidence concerns the gene AKT1 and glioma.