Fig. 1. PROMIS allows for system-wide detection of protein–small molecule and protein–protein complexes using size exclusion chromatography.

a Dividing yeast cells were harvested in the logarithmic phase of growth and were used as a source of endogenous protein–protein and protein–metabolite complexes. Complexes were fractionated using size exclusion chromatography, lyophilised and subjected to methyl tert-butyl ether-methanol-water extraction. Polar metabolites and proteins were analysed by liquid chromatography-mass spectrometry. b Known yeast protein macro-complexes remain intact. Multiple subunits of known protein macro-complexes co-elute together. The peak elution profiles of the components of 14 known protein macro-complexes are depicted (Supplementary Data S7 and S8). The intensity was calculated relative to the maximum intensity of a given protein measured across size exclusion chromatography separation range. Distinct colours are used to mark different protein macro-complexes. c The receiver operating characteristic curve represents a trade-off between numbers of captured true-positive and false-positive protein–metabolite interactions by varying the Pearson correlation coefficient (PCC) (Supplementary Data S10). The red dot indicates the chosen threshold (PCC ≥ 0.7) used for determining complexes. d Interaction network of captured known protein–metabolite complexes. Overall, 14 of the 87 known protein–metabolite interactions were re-captured in the PROMIS experiment (Supplementary Data S9).