Fig. 4

The dMHBs and the potential effects of DNA methylation at regulatory regions on gene expression. A Heap map of top 50 most variable dMHBs. B The length and CpG density distribution of dMHBs. C Co-localization of dMHBs with genomic functional regions. CGI: CpG islands. D Enrichment of dMHBs at genomic functional regions. E An example of dMHB (Chr29:47439984:47440080) showing the coordinated methylation of CpG sites in the same dMHB. F Global relationship (significant negative correlation) between promoter methylation level and gene expression level. Each dot symbolizes a specific gene. Blue dots indicate that gene expression and methylation level changes for the corresponding gene were not statistically significant (Gaussian Mixture Model p > 0.005). Conversely, red dots represent differential genes with significant changes in both gene expression and methylation levels of their promoters (Gaussian Mixture Model p < 0.005). Red dots out of gray shadow represent differential genes with significant changes in the methylation level of promoter (greater than 10% changes) and gene expression level (|log₂FC|≥ 1) between S. aureus-positive (SAP) and healthy control (HC) groups. G The top 10 most significantly enriched known motifs for transcription factors in hyper- and hypo-methylated dMHBs located at regulatory regions and significantly associated with gene expression (GE-dMHBs). H, I Examples of de novo (discovered) motifs in hypo-methylated GE-dMHBs (hypo_VGGAAR) (H) and hyper-methylated GE-dMHBs (hyper_CNGGRA) (I), showing high similarity with known motifs for transcription factors. Detailed data on the depicted findings are found in Supplementary Tables 10, 11 and 14