Fig. 7: Within-module pairwise Pearson correlation for the Extracellular Matrix Production & Cell Membrane module (m13) stratified by exacerbation frequency.

Boxplots depict the distribution of median gene-gene Pearson correlation values from the Extracellular Matrix Production & Cell Membrane module (m13) when calculated by iterative downsampling in the mepolizumab treatment arm at each time point. For each iteration, 15 individuals were randomly removed from one of 3 within treatment arm exacerbation subgroups (those with either 0, 1, or ≥2 exacerbations during the study), and the median correlation among the remaining samples was recorded. This was repeated 1000 times for each exacerbation subgroup. The resultant distribution of these median values indicates the relative contribution of each exacerbation subgroup on the overall observed module correlation for the group, thereby highlighting the relative effect of each subgroup on the module median correlation. Notably, in the mepolizumab on treatment group, when individuals were removed from the ≥2 exacerbation subgroup the correlations were lower than the group-level median indicating individuals with ≥2 exacerbations disproportionately drive the observed higher module correlation on mepolizumab treatment. The opposite is true for individuals in the 0 exacerbation subgroup, they contribute the least to the observed higher module correlation on mepolizumab treatment. Boxes show the interquartile range (IQR), whiskers extend to 1.5 × IQR. Solid black lines correspond to the overall group level within-module pairwise Pearson correlation for each time point corresponding to Fig. 1 (not stratified by exacerbation frequency). The left-hand boxplot (gray) indicates the effect of balanced random downsampling of 15 individuals where 5 individuals come from each of the 3 exacerbation subgroups on each iteration as comparison. Statistical annotations indicate mean p < 0.05* and mean p < 0.01** in two-sided t-test contrasting the full DGC Z-Score distributions for each exacerbation group downsampling relative to the balanced downsampling, and are averaged across 1000 random iterations. p-values (left to right) = 0.0118; 0.0176; 0.0107; 0.0094; 0.0125; 0.0062.