Fig. 3

Network analysis reveals five exacerbation-associated gene modules. Network analysis (WGCNA) was performed utilising the top ~ 4000 most variable genes, in (A) heatmap of the gene networks with hierarchical clustering gene dendrograms where each column and row represent single genes. Red colour indicates highly co-expressed clusters of genes or gene networks across the diagonal, and lighter colour in white/yellow indicates low co-expression, in (A, B) the data clustered into 11 co-expression modules denoted modules A-K, and the overall expression of the modules was determined using eigengene values contrasting acute exacerbation versus convalescence. Wilcoxon signed ranked test was used to test for differences between the acute and convalescent visits (AV/CV). *,<0.05, **,<0.01. In (C) putative molecular drivers were identified for the significant modules with Ingenuity Pathways Analysis from the Ingenuity Knowledge Base. Red = activated driver, blue inhibited driver. Absolute activation Z-scores ≥ 2.0 and P-values ≥ 0.01 were deemed significant. FTP = fluticasone propionate, DEX = dexamethasone, CpG ODN = CpG oligodeoxynucleotide. (D) Reconstruction of the wiring diagram of the innate immunity module J and visualisation using Cytoscape. Coloured node = present in the original network (zero order network), white node = transcription factors