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

Figure 3

Integrative multiomic study in hepatocytes with PKLR perturbation. (a) Integrative transcriptomic and nontargeted metabolomic analysis identified the variations on pathways of linoleic acid metabolism in hepatocytes with overexpressed PKLR. (b) Integrative transcriptomic and nontargeted metabolomic analysis identified the variations on pathways of linoleic acid metabolism in hepatocytes with downregulated PKLR. (c) Integrative transcriptomic and nontargeted metabolomic analysis identified the variations on pathways of glycerophospholipid metabolism in hepatocytes with overexpressed PKLR. (d) Integrative transcriptomic and nontargeted metabolomic analysis identified the variations on pathways of glycerophospholipid metabolism in hepatocytes with downregulated PKLR. (e) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of glycolysis in hepatocytes with overexpressed PKLR. (f) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of glycolysis in hepatocytes with downregulated PKLR. (g) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of citrate cycle in hepatocytes with overexpressed PKLR. (h) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of citrate cycle in hepatocytes with downregulated PKLR. (i) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of arginine biosynthesis in hepatocytes with overexpressed PKLR. (j) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of arginine biosynthesis in hepatocytes with downregulated PKLR. (k) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of pyruvate metabolism in hepatocytes with overexpressed PKLR. (l) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of pyruvate metabolism in hepatocytes with downregulated PKLR. (m) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of butanoate metabolism in hepatocytes with overexpressed PKLR. (n) Integrative transcriptomic and targeted metabolomic analysis identified the variations on pathways of butanoate metabolism in hepatocytes with downregulated PKLR. (o) Network connection for variations of key metabolites from targeted metabolomics in hepatocytes with overexpressed PKLR. In (a–n), the frame in rectangle represented the genes involved in pathways; the frame in ellipse or circle represented the metabolites involved in pathways. In (o), the frame in green represented downregulation, and the frame in red represented upregulation in cells with PKLR overexpression.

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