Fig. 4

Proof of concept biochemical network study. Inset right: Prototypical biochemical network with six metabolites and seven reactions modeled using the hybrid cybernetic approach (HCM). Intracellular cellmass precursors A,B, and C are balanced (no accumulation) while the extracellular metabolites A _e ,B _e , and C _e are dynamic. The oval denotes the cell boundary, q _j is the jth flux across the boundary, and v _k denotes the kth intracellular flux. Four data sets (each with A _e ,B _e ,C _e and cellmass measurements) were generated by varying the kinetic constants for each biochemical mode. Each data set was a single objective in the JuPOETs procedure. a Ensemble simulation of extracellular substrate A _e and cellmass versus time. b Ensemble simulation of extracellular substrate B _e and C _e versus time. The gray region denotes the 95% confidence estimate of the mean ensemble simulation. The data points denote mean synthetic measurements, while the error bars denote the 95% confidence estimate of the measurement computed over the four training data sets. c Trade-off plots between the four training objectives. The quantity O _j denotes the jth training objective. Each point represents a member of the parameter ensemble, where gray denotes rank 0 sets, while black denotes rank 1 sets. Ensembles were generated using POETs without employing local refinement