Fig. 2. Metabolic pathways associated with mortality.
(A) Pathways associated with metabolomic alterations in NS. Pathway impact indicates the sum of importance of the altered metabolites in the impacted pathway based on pathway topology; the −log(P) are test statistics for quantitative pathway enrichment analysis based on concentration differences between groups. Impacted pathways are above the dashed lines [impact >0.2 and −log(P) >5]. (B) Differential correlation network of metabolites. Nodes are metabolites, and edges connect metabolite pairs with differential correlations between groups (P∆r < 0.05). Solid edges denote increased and dashed edges denote reduced strengths of correlation in NS. The relative width of edges corresponds to the absolute difference in correlation strengths. Since no reversed correlation was detected, positive correlations are indicated by red and negative correlations are indicated by blue edges. Node color and size correspond to metabolite classes and node degree, respectively. (C) Mapping of univariately altered metabolites onto impacted pathways. Metabolites boxed in dark red or blue rectangles were significantly increased or decreased in NS (PFDR < 0.05), respectively; those in light red or blue showed marginal increase or decrease in NS (PFDR < 0.1); those boxed in white were comparable between groups. Grayed out metabolites were not measured. Right panel listed concentrations of key TCA cycle metabolites.