Fig. 5

Time-dependent eigengene analysis. We analyzed the evolution of eigengene levels over time. (a) We projected the timepoint medians onto the leading principal components of the eigengene expression, and charted the median timecourse (blue) on a biplot. We then separated the survivors (green) and non-survivors (red), revealing an exaggerated innate immune and metabolic first step in non-survivors. (b) We made a heatmap of the median values for each eigengene at each timepoint. Each row is scaled to z-scores to bring out temporal contrasts, where red is upregulated and green is downregulated. Here, we ordered the rows by sorting z-scores at day 1. We found a response to surgery orchestrated into stages: first, activation of the innate immune response, followed by anti-inflammation, and finally reparative processes such as mitosis, coagulation, and apoptosis. (c) To infer which eigengenes are related to survival outcomes, we fit a multivariate mixed-effects Cox model to the eigengenes (asterisks), and univariate Cox models at each timepoint (uncorrected p-values displayed), and made a heatmap using signed –log p values (where the sign comes from the model coefficient). Note that the reparative (yellow) supercluster emerges as important in the last two timepoints, along with the Type I IFN module. The mitosis and defense modules, marked by significant p-values, are related to cellular regeneration and extracellular matrix (ECM) degradation, and suggest organ failure due to disseminated coagulopathy