To more formally evaluate potential

To more formally evaluate potential mechanistic links between DA enzymes and metabolites, we repeated the clustering and association procedures described above in the context of metabolite-species associations. Metabolite-enzyme associations followed many of the same patterns observed for species and enzymes: association density was low (3%), suggesting that most metabolites associated with only a few enzymes (and vice-versa), and the vast majority of interactions (95%) were concordant with IBD pathogenesis (Supplementary Fig. 11). Several associations occurred between standard metabolites and the enzymes discussed above. For example, magnesium-importing ATPase was strongly negatively associated with 2-hydroxymyristic acid (a control-enriched compound; Spearman's r=−0.492; Fig. 5F). Conversely, precorrin-2 dehydrogenase was positively associated with caproic acid (another control-enriched compound; r=0.507). While such relationships are consistent with compounds acting as enzyme substrates and products (respectively), this does not appear to be the case for these specific enzyme:compound pairs, suggesting that other factors likely mediate their associations (e.g. encoding by/interaction with subsets of IBD-associated species).