Fig. 2
DNAm signatures of TB exposure in alveolar macrophages and alveolar T cells. A, D Multidimensional scaling (MDS) analyses of controls and TB-exposed/patient samples. MDS plot of dimension 1 (x-axis) and dimension 2 (y-axis) showing the distances between the samples using the top 1000 most variable CpG positions of the alveolar macrophages (A) and alveolar T cells (D). B, E EnhancedVolcano plot of the differentially methylated CpG-sites (DMCs) separating the controls from the TB-exposed/patient group in the alveolar macrophages (B) and alveolar T cells (E). Each dot represents a comparison of mean methylation at an individual CpG site. The x-axis is the mean methylation difference (MMD) with vertical line representing a cut-off MMD > + -0.2. The y-axis is the negative log10 of adjusted p-value with the cut off FDR p-value of 0.05 shown with dash-dotted horizontal line. Blue CpGs, hypomethylated; red CpGs, hypermethylated. C, F Heatmap analysis of the alveolar macrophages (C) and alveolar T cells (F) revealing a distinct DNA methylation pattern of the controls and TB-exposed and patient group. The heatmap is plotted from the absolute β-values of the top DMCs differentiating the groups. Cluster dendrogram is calculated using the Euclidean distance method. DNAm, DNA methylation; TB, tuberculosis; MDS, multidimensional scaling; DMC, differentially methylated CpG-site; MMD, mean methylation difference; FDR, False Discovery Rate; Con, control group; Exp, TB-exposed; Pat, TB patients; F, female; M, male; ND, no data; IGRA, interferon-gamma release assay