Fig. 2: Discovery of previously unknown metabolic reactions through isotopologue similarity networking.
a Workflow for the isotopologue similarity networking approach. Red dot represents known metabolites and blue dot represents unknown metabolites. b The isotopologue similarity network in 293T cells labeled with mixed tracers ([U-13C]-glutamine, [U-13C]-glucose, and [U-13C]-acetate) for 17 h. Nodes represent labeled known (red) and unknown (black) metabolites; edges represent that two metabolites shared similar isotopologue patterns and MS/MS spectra. c Numbers of known and unknown labeled metabolites in the network. d Numbers of known and unknown reactions in the network. The reactions between known and unknown metabolites were defined as unknown I. The reactions between unknown metabolites were defined as unknown II. Red dot represents known metabolites and blue dot represents unknown metabolites. e Retrieval of 86 known reactions from KEGG: the recall rate (left) and reaction step distribution (right). f Statistics of reaction classes for unknown reactions. g Top 6 ranked reaction types with indicated atom exchanges in unknown reactions. Source data are provided as Source Data files for Fig. 2c–g.
