Integrative Network Analysis Revealed Genetic Impact of Pyruvate Kinase L/R on Hepatocyte Proliferation and Graft Survival after Liver Transplantation

Figure 5

Weighted correlation network analysis on nontargeted metabolome of grafts and its connections with clinical factors. (a) Cluster dendrogram obtained by dissimilarity based on consensus topological overlap with the corresponding modules indicated by the color row. Each colored row represented a color-coded module containing a group of highly connected metabolites. (b) Relationships of consensus module and clinical features of LT cases. Each row in the table corresponded to a consensus module, and each column corresponded to a feature. The module name was shown on the left side for each cell. Numbers in the table reported the correlations of the corresponded module and feature, with the values printed below. The table is color coded by correlation according to the color legend. Intensity and direction of correlations are indicated on the right side of the heatmap. (c) Dendrogram of consensus module and heatmap of the adjacencies obtained by WGCNA on the consensus correlation. Numbers in the table reported the intermodule correlations, with the values printed below. The table was color coded by correlation according to the color legend indicated on the right side of the heatmap. (d) Scatterplot of metabolite significance PKLR vs. MM in the green module. (e) Results for pathway enrichment based on metabolites in the green module. (f) Details of arachidonic acid metabolism and related metabolites involved in module. (g) Scatterplot of metabolite significance PKLR vs. MM in the brown module. (h) Scatterplot of metabolite significance PKLR vs. MM in the turquoise module. (i) Coexpression network by top 20 nodes based on coexpressed links in positive metabolites from nontargeted metabolomics of hepatocytes. (j) Coexpression network by top 10 nodes based on coexpressed links in positive metabolites from nontargeted metabolomics of human grafts for transplantation. (k) Coexpression network centered by C00157 and C04230 based on coexpressed links from nontargeted metabolomics of hepatocytes. (l) Coexpression network centered by C00157 and C04230 based on coexpressed links from nontargeted metabolomics of grafts for transplantation. Abbreviations: LT: liver transplantation; MM: module membership.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

(j)

(k)

(l)