Figure 2
Metabolic pathways with an altered flow in patients with Crohn's disease (CD) versus control patients. The Flux Balance Analysis/Random Forest framework outlined in Fig. 1 were applied to the RISK dataset. After obtaining the list of top metabolic reactions that were altered between CD and control groups, these reactions were grouped into "families" (A–D) based on the biological processes they were involved in: (A) ATP transport processes were found to have significant rates of flux. (B) Mevalonate pathway. Several enzymes within the mevalonate pathway were altered in patients with CD, including the exchange of R- mevalonate, hydroxymethylglutaryl coenzyme A reversible mitochondrial transport, transport of R- mevalonate, and R- mevalonate NADP + oxidoreductase (CoA acylating), (C) Fatty acid oxidation. Long-chain-acyl Coenzyme A dehydrogenase, linoleic acid transport, and alpha-linolenoyl-CoA exchange (D) Uridine transport and exchange. For all graphs, the x-axis describes the reaction that is altered between controls (orange) and diseased states (blue). The y-axis shows the flux values generated by RIPTiDe by analyzing the flow of metabolites through an ileal-specific metabolic network reconstruction. The scale of flux values (y-axis) varies with the reactions as the efficiency of different metabolic pathways in generating biomass varies in a given biological system. A Mann–Whitney U test was done to compare reactions that varied between patients with Crohn's disease and controls. The stars (*) are used to flag levels of significance. *p < 0.05, **p < 0.01, ***p < 0.001. AMP: adenosine monophosphate; ATP: adenosine triphosphate; ER: endoplasmic reticulum; NADP + : nicotinamide adenine dinucleotide phosphate CoA: Coenzyme A.
