Extended Data Fig. 3: Directionally constrained reactions in the PFM and OFM.
From: A systems-level, semi-quantitative landscape of metabolic flux in C. elegans
(a-c), Randomizations (n = 10,000 in all) showing that: the percentage of nonresponsive genes conflicting with another responsive gene in the same reaction was significantly lower than random (a), total flux through reactions associated with no responsiveness in iMAT-WPS integration was significantly lower than random (b) and the objective value of WPS similarity integration (x-axis) based on real WPS data was significantly better optimized (minimized) than random (c). Red dashed lines indicate the percentage in the real WPS data and histograms in randomized data. The empirical P values are indicated. d, Bar graphs showing the number of directionally constrained reactions in the PFM. Grey indicates overlapped (identical) reactions in all five integrations; orange indicates overlapped reactions in four integrations except for the no-integration case (i.e., with only the biomass production constraint); and white indicates reactions that are different in individual integrations. e, f, Venn diagrams showing the number and overlap of directionally constrained reactions when different data were integrated, in the PFM (e) and OFM (f). g, Proportions of directionally constrained reactions in iCEL1314 model. We visualized the proportions for all reactions in the model (‘all’) and three mutually exclusive categories: ‘exchange’ for exchange reactions; ‘transport’ for transporter reactions; and ‘internal’ for all other reactions. h, Proportions of directionally constrained reactions in OFM ordered by pathways. Pathways are defined with the ‘subSystems’ annotation in the iCEL1314 model. Pathways enriched for directionally constrained and unconstrained reactions are colored in red and blue, respectively (BH-adjusted, one-sided hypergeometric test Padj < 0.01). The green dashed line indicates the cumulative number of directionally constrained reactions from left to right. i-j, Examples of flux solution space (upper and lower bounds) obtained by Flux Variability Analysis (FVA) for two different iCEL1314 reactions. The flux value in OFD, solution space of OFM and PFM are visualized together as indicated. The solution spaces obtained by different integration approaches, as indicated at the left of each figure, are compared side-by-side. Exp: integrating gene expression levels; resp: integrating WPS responsiveness; simi: integrating WPS similarity.
