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Accurate prediction of flux distributions compatible with metabolite concentration effects in genome-scale metabolic networks

Fig 4

Performance of logit regression models for metabolite concentration effects and evaluation of predicted flux distributions in S. cerevisiae.

A. The histogram illustrates the performance of the logit regression models in predicting metabolite concentration effects, η, based on their adjusted . The data set comprises 281 reactions, each with more than 10 entries corresponding to different S. cerevisiae conditions. Among these, 73 reactions achieved an adjusted greater than 0.6, used in the constraint-based optimization problem. B. The plot compares the predicted flux from the optimization problem with the estimated flux for the reaction r_0569 (inorganic diphosphatase), resulting in a Pearson correlation coefficient of 0.95 (p-value= . C. The histogram presents the number of reactions based on the Pearson correlations between their predicted and estimated fluxes. In total, there are 418 reactions with at least 80% non-zero estimated fluxes across different conditions. More than 80% of these reactions have a Pearson correlation greater than 0.8 between estimated and predicted fluxes. D. Comparison of the predicted flux distribution with the estimated flux distribution for a representative condition, Yu2021_N30_035R2, which corresponds to the second biological replicate of nitrogen-limited chemostat growth at a dilution rate of 0.35 and a carbon-to-nitrogen (C/N) ratio of 30 [39]. The fluxes are logarithmically transformed, with a small constant () added to all values to avoid taking the logarithm of zero. The Pearson correlation between the predicted and estimated fluxes is 0.86 (p-value = 0.0). A prediction interval band, corresponding to a 90% confidence level, is included. The reactions inside the prediction interval band are considered to have well-predicted fluxes. Highlighted reactions outside of the confidence region include: r_1021_f (succinate dehydrogenase (ubiquinone-6)), r_0815_b (O-succinylhomoserine lyase (L-cysteine)), r_0326_f (dCMP deaminase), r_3533_b (NAD transport, cytoplasm-ER membrane), r_1128_f (citrate transport), r_3534_f (glycerol 3-phosphate transport, cytoplasm-ER membrane), and r_1112_b (AKG transporter) E. The mean and standard deviation of the proportions of reactions with well-predicted fluxes across subsystems for all conditions. We limited the subsystem to those with more than 30 reaction. The value above each bar indicates the number of conditions in which the subsystem is significantly enriched with reactions exhibiting well-predicted fluxes, determined using a hypergeometric test with Bonferroni-corrected p-values below the 0.02 threshold.

doi: https://doi.org/10.1371/journal.pcbi.1014066.g004