Fig. 1

Global analysis of DNA methylation changes in septic monocytes. a Representative flow cytometry profiles indicating the sorting strategy and gates used in this study. Monocytes (MOs) (CD14+ CD66b−) were sorted from healthy controls and patients (SIRS and sepsis). b Principal component analysis (PCA) of methylation heatmap data for control, SIRS, and septic monocytes (in blue, green, and red respectively). c DNA methylation heatmap showing differentially methylated CpGs between controls (CON, blue) and patients with sepsis (SEP, red). The heatmap includes all CpG-containing probes displaying significant methylation changes (15% of differential of beta values, p < 0.01 and false discovery rate (FDR) < 0.05). A scale is shown at the bottom left ranging from − 2 (lower DNA methylation levels, blue) to + 2 (higher methylation levels, red). d Gene ontology (GO) analysis of genes associated with differentially methylated CpG sites showing the most relevant and significantly enriched categories resulting from the Genomic Regions Enrichment of Annotations Tool (GREAT). e Enrichment analysis of the different chromatin states for CpG sites corresponding to each methylation cluster (left to hypermethylation, right to hypomethylation). The relative enrichment of the different states is represented using the odds ratio. Dot size represents the FDR value. Tss, transcription start site; Enh, enhancer; Repr, repressed region; PC, Polycomb. f TF binding motif analysis of differentially methylated CpGs between control and sepsis. The panel shows fold change (FC), TF family and factor (selected TF with p ≤ 1e⁻⁰⁵ for hypermethylated regions and p ≤ 1e⁻⁰³ for hypomethylation). Motif logo is representative of the TF family. g Box plots showing β-values obtained from the DNA methylation array. We observed hypermethylation and hypomethylation in important immune system genes. The CpG sites are marked with a green line in the gene scheme placed on top of each graph, where the TSS is marked with a red arrow