Supplementary Figure 4: Validation analyses demonstrate the core exacerbation modules are reproducible.

(a) Module expression levels for the 6 exacerbation core modules are shown comparing the full cohort (154 total events), the paired cohort (38 total events), and the unpaired cohort (116 total events). The paired cohort included 19 participants who experienced one Ex+ and one Ex- event during the study. The unpaired cohort compared participants who contributed only Ex+ or only Ex- events, and included the other 87 participants who collectively had 28 Ex+ and 88 Ex- events. The two groups were, by definition, independent of one another. The four core modules that were significantly higher in Ex+ events (left-most four plots) have an FDR<0.05 in each comparison. The two modules that were significantly lower in Ex+ events (right-most two plots) have an FDR<0.05 in the full and unpaired cohorts and FDRs of 0.06 (Lymphocyte proliferation) and 0.22 (BCR signaling) in the paired cohort. Expression levels represent the log base 2 of the geometric mean of the normalized expression of all genes within the module. Shown are the group mean and standard error values. (b) A sensitivity analysis demonstrates the proportion of times each module was significant using iterative boot strapping to random subsets to 80% of participants. The first 6 modules are the core modules shown in (a) and were significant in >99% of iterations. The 13 modules in blue are those that were significant in the primary analysis. Modules that were never significant are not shown. Abbreviated alphanumeric module names are listed for brevity. (c) Shown are the associated log2 fold change values for the sensitivity analysis. Calculated fold changes across all iterations are shown as box plots of the medians, interquartile ranges (boxes), and 1.5 times the interquartile ranges (whiskers) with outliers shown as points. The red line indicates the 13 modules significant in the primary analysis. Abbreviated alphanumeric module names are used for brevity.