Fig. 4
Correlation between DNA methylation and gene expression. A UMAP visualization showing the immune cell populations identified from Louvain clustering and cell-specific marker gene expression. B Dot plot representing the expression of selected marker genes identified in the cell population. The scale represents the mean gene expression level in the cell subset and the circle size represents the percentage of cells in the subset of expressing cells. C Heatmap representing differentially expressed genes (DEGs) with a log2(FC) > 0.6, above, and log2(FC) <  − 0.6, below. Genes overexpressed and downregulated in COVID-19 patients in relation to HDs are depicted in red and blue, respectively. D Gene ontology (GO) overrepresentation of GO Biological Process categories comprising the upregulated and downregulated DEGs. The odds ratios for each group and the − log2(FC) are shown. Selected significant categories (FDR < 0.05) are shown. E Discriminant Regulon Expression Analysis (DoRothEA) of COVID-19 severe patients compared with HDs. Normalized enrichment score (NES) and log2(FC) of transcription factor expression are depicted. F Correlation of average DNA methylation levels of DMPs with average gene expression of DEGs in the HDs vs. COVID-19 severe patients. Log2(FC) of expression is plotted on the y-axis, higher numbers representing a higher level of expression in COVID-19 and lower numbers a higher level of expression in HDs. DNA methylation is depicted on the x-axis as Δβ, lower numbers representing a lower level of methylation in COVID-19 monocytes, and higher numbers a lower level of methylation in HDs. Points are colored according to their genomic context. G Gene set enrichment analysis (GSEA) of HD vs. COVID-19, using hypomethylated-associated genes and hypermethylated-associated genes as genesets. The running enrichment score is represented, and the normalized enrichment score (NES) is shown above (FDR < 0.01). H Representation of individual DNA methylation values of DMPs from the hypermethylated and hypomethylated clusters (beta values), the position in respect to the transcription start site, and the relative expression of the closely related DEGs. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.0001, **** p < 0.00001