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

Figure 1

Comprehensive analysis on nontargeted metabolomic results in cells with PKLR variations. (a) PCA revealed clear separation in nontargeted metabolomic data from hepatocytes with overexpressed PKLR, dots in blue [2] represented the samples with overexpressed PKLR, and dots in green [1] represented the corresponded NC samples. (b) Validation of OPLS-DA model by class permutation analysis for (a). (c) PCA revealed clear separation in nontargeted metabolomic data from hepatocytes with overexpressed PKLR, dots in blue [2] represented the samples with downregulated PKLR, and dots in green [1] represented the corresponded NC samples. (d) Validation of OPLS-DA model by class permutation analysis for (c). (e) Correlation on FC of each metabolite in the group with PKLR overexpression and downregulation. (f) Heatmap of metabolites showed significant association with PKLR overexpression. (g) Heatmap of metabolites showed significant association with PKLR downregulation. (h) Heatmap of metabolites showed both significant associations with PKLR overexpression/downregulation. (i) Volcano plot to visualize both FC and significance for each metabolite compared between hepatocytes with PKLR overexpression and corresponded NC, red dots represented significantly higher metabolites () in the group with overexpressed PKLR, green dots represented significantly lower metabolites () in the group with overexpressed PKLR. (j) Volcano plot to visualize both FC and significance for each metabolite compared between hepatocytes with PKLR downregulation and corresponded NC, red dots represented significantly higher metabolites () in the group with downregulated PKLR, and green dots represented significantly lower metabolites (, ) in the group with downregulated PKLR. (k) Correlation heatmap for the top 20 metabolites that are associated with PKLR overexpression; the table is color coded by correlation according to the color legend; legend on intensity and direction of correlations is indicated on the right side of the heatmap. (l) Correlation heatmap for the top 20 metabolites that are associated with PKLR downregulation; meaning of legend was the same as (j). (m) Correlation heatmap for the top 20 metabolites that are both associated with PKLR overexpression/downregulation; meaning of legend was the same as (j). (n) Metabolites showed to have association with PKLR overexpression/downregulation by KEGG ID. (o) Overlapped metabolites between PKLR OV and SI groups. (p) Pathway analysis from nontargeted metabolomics based on positive metabolites that are associated with PKLR expression. (q) Details of pathway on glycerophospholipid metabolism and positive metabolites associated with PKLR expression. (r) Details of pathway on linoleic acid metabolism and positive metabolites associated with PKLR expression. Abbreviations: FC: fold change; NC: negative control; OV: overexpression; PCA: principal component analysis; SI: silence.

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