Predicted oncometabolites.

(A) LoF oncometabolites. Metabolites surrounded by reactions with significantly changed flux in the mutated enzyme deficient model compared to the normal model were finally predicted as the potential LoF oncometabolites. The heatmap shows predicted oncometabolites (black) across nine mutated enzyme deficient cancer models ([m], [c] and [e]: metabolites observed in mitochondria, cytosol, and extracellular, respectively). (B) GoF oncometabolite substructures. By applying the chemoinformatics approach, promiscuous catalytic activities of enzymes resulting from their GoF mutations were predicted. The heatmap represents predicted dominant substructrues of promiscuous substrates and products across seven cancer types. Full list of substructrues of promiscuous substrates and products is shown in the Table S8 in Text S1.