Fig. 4

Ontology analysis of genes annotated to differentially methylated CpG sites. A- The list of 1022 genes annotated to the first 1500 differentially methylated CpGs (ordered by statistical significance) was analyzed using the EnrichR tool online (45). The first 20 cognitive impairment, neurodegenerative and psychopathological disorders categories were selected for the lollipop graph showing gene count (size of the circle) and -Log10 (p value) (color scale) from the DisGeNET category (within “Disease and Drugs” categories of EnrichR; B- Heatmap depicting the genes in each category presented in the lollipop graphs (red squares indicate the gene belongs within the category; blue squares indicate genes annotated to EMN CpG sites). C- Network representation of the EMN genes in the list (see B); blue and green circles indicate DisGeNET categories and genes, respectively (prepared with EnrichR-KG tool). D- EMN genes associated with cognitive and neuro-psychopathology categories according to the DisGeNET database. Dark blue squares indicate genes within each category. The upper boxplot shows the contribution of each category to the EMNs calculated as the median of the contribution of all the genes associated with each category. The white-blue-red column indicates EMN contribution of the listed genes