Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model
(A) Overlap of gene activity predictions with genes expressing above the significance threshold. Regions of the diagram are approximately proportional to their associated set sizes. The magenta circle represents the set of genes predicted active in the reduced kidney model. The cyan circle represents the set of Recon1-associated genes with expression levels above the significance threshold in the kidney tissue data. The yellow circle represents the set of genes encoding proteins that were detected in normal human kidney glomerulus tissue. (B) Renal metabolic objectives supported by predicted reaction flux states. The orange circle represents renal metabolic objectives supported both by the kidney model developed in this study and a kidney model derived from the reaction activity predictions of Shlomi et al. The red circle represents renal metabolic objectives supported only by the kidney model from this study. Metabolite abbreviations are defined in Table 1.