Extended Data Fig. 4: Statistical properties of pairwise correlations in MPCA.
From: Covariation MS uncovers a protein that controls cysteine catabolism
(a) Linking accessory proteins and metabolites of known Reactome pathways. Red nodes, known members of established networks; blue nodes, neighboring proteins or metabolites; orange node, the protein or metabolite to test; gray nodes, all other proteins and metabolites in MPCA. (b) Reactome pathways and newly identified accessory proteins in BAT. (c) Reactome pathways and newly identified accessory proteins in liver. (d) TCA cycle with an accessory metabolite in BAT. (e) Glutathione synthesis and recycling pathway with accessory members in liver. (f) Fold enrichment over random selection of MPCA pairwise correlations recapitulating physical interactions in RHEA and TCDB. MPCA correlations were filtered to contain proteins and metabolites existing in RHEA and TCDB. (g) Rank of metabolites measured in MPCA based on the number of protein-metabolite intractions in RHEA and TCDB. (h) Fold enrichment over random selection of MPCA edges involving ADP, NAD, and AMP recapitulating physical interactions in RHEA and TCDB, compared to all other edges. (i) Schematic of “hop” analysis to examine physical interactions and non-specific interactions underlying protein-metabolite correlations in MPCA. (j) The number of protein-metabolite edges included in each “hop”, 1-hop means physical interactions. The percentage annotates proportion of all possible protein-metabolite edges. (k) Fold enrichment over random selection of MPCA edges recapitulating physical interactions in RHEA and TCDB, compared to non-specific interactions introduced from the “hop” analysis. Fold enrichment normalized to 2-hop. (l) Fold enrichment over random selection of MPCA edges recapitulating physical interactions in RHEA and TCDB, compared to non-specific interactions introduced from the “hop” analysis. Fold enrichment normalized to 3-hop. (m) ROC curves of pairwise correlation analysis (gray), LASSO analysis (red, referring to Fig. 2a), and null distribution (black). AUC- area under the curve. (n) PR curves of pairwise correlation analysis (gray), LASSO analysis (red, referring to Fig. 2a). AP- average precision. (One-sided Fisher’s exact test with Benjamini-Hochberg p value correction in d,e).
