Fig. 5.

Multi-omics model of endotoxin tolerance in circulating monocytes obtained during the acute and recovery stage of community-acquired pneumonia. A Heatmap of percent variance explained (coefficient of determination, R²) per projection-to-latent-structure (PLS) component (1–4) for monocyte ex vivo cytokine production levels, DNAse hypersensitive site (DNAse-HS; 109,925 sites) DNA methylation levels and RNA transcriptomes (32,630 transcripts). B Density plots of percent explained variation in study groups per PLS component 1 and 2. C Clustered image heatmap of the most informative transcripts (n=492) and DNAse-HS methylation levels (n=92), taking loading vectors in the upper or lower 20% of the distribution in component 1, as well as ex vivo cytokine levels of TNF, IL-1β, IL-6, and IL-10. D Bar plots illustrating significantly enriched (multiple-test adjusted p < 0.05) Ingenuity canonical signaling pathways for PLS component 1 or 2. E Circular plot of tightly correlating (Pearson correlation cutoffs set at ≥ 0.55 or ≤ −0.55) ex vivo cytokine levels, RNA transcripts and DNAse-HS methylation levels in PLS component 1. F, G) Dot plots integrating percent methylation levels at DNAse-HS-Chr22, RNA expression levels of cholesterol biosynthesis genes SQLE, DHCR24, and FDFT1, as well as levels of IL-1B (F) and IL-10 (G) after ex vivo LPS exposure. Blue line denotes the line-of-best-fit and confidence intervals