Fig. 3
DNA methylation changes in septic monocytes parallel the increase of IL-10 levels. a Cytokine measurement using cytometric bead array (CBA) from control and septic PBMCs before and after LPS stimulation (t = 3 h). Box and whisker plots show median values. Mann-Whitney test was used to determine significance (*p < 0.05, **p < 0.01, and ***p < 0.001). b DNA methylation heatmap of CpG changes in relation to IL-10 basal concentration (represented on the top of the heatmap as log scale). Spearman’s correlation was used with p < 0.01, r > 0.5, and Δβ ≥ 0.15. A scale is shown at the bottom, wherein beta values range from − 4 (lower DNA methylation levels, blue) to + 4 (higher methylation levels, red). c Violin plots corresponding to the 5mC-normalized data for control and sepsis presented in the heatmap in the previous section. The median and the interquartile range are represented. d Chromatin state characterization of differentially methylated sites for section b. The relative enrichment of the different state assignments is representing using the odds ratio. FDR is represented by the size of the dots. e Bubble scatterplot of TF enrichment for hypermethylated and hypomethylated CpGs. The x-axis shows the percentage of windows containing the motif, and the y-axis shows the fold enrichment of the motif. Bubbles are colored according to TF family. p value is indicated by the bubble size (selected TF with p < 1e−07 for hypermethylated and hypomethylation regions). f GO categories resulted from GREAT analysis of differentially methylated CpGs related to IL-10 concentration. g Genomic tracks representing the clusters of differentially methylated CpGs for protocadherins (PCDH, upper scheme) and human leukocyte antigen (HLA, lower panel). Blue and red lines represent the confidence intervals for each average values. A window of ± 50,000 bp was used