Figure 4

Validating BOSS on the S. cerevisiae central metabolic network. The results of BOSS (blue line and dots) when applied to the S. cerevisiae central metabolic network are illustrated and contrasted by the hypothesized objective reaction (i.e., precursor biomass synthesis) (open black circles). Panel (a) illustrates the results when the hypothesized objective reaction of precursor biomass synthesis is excluded from the network inputted into BOSS. Panel (b) depicts the results when the network is inputted into BOSS with the hypothesized objective reaction. Note that the entire experimental flux distribution was provided as input to BOSS in both cases. When the precursor biomass synthesis objective reaction was excluded from the network inputted into BOSS, the sum-squared error between the BOSS-derived objective reaction and the expected precursor biomass synthesis objective reaction, normalized to the magnitude of the precursor biomass synthesis objective reaction (SSE _S ), was 8.242 × 10^-29 (panel (a)). By contrast, when the precursor biomass synthesis objective reaction was included in the set of stoichiometric reactions inputted into BOSS, the SSE _S for the BOSS solution was approximately 655.0 (panel (b)). Panel (c) depicts a plot of the sum-squared error between the BOSS-derived and the corresponding reaction when the flux for each of the 62 reactions in the system was excluded from the pool of experimental fluxes one by one. The smallest SSE _S values were 42.20 and 4.210 × 10^-4 and corresponded to the ATP maintenance and biomass production reactions, respectively. Consequently, as shown in panel (d), BOSS was able to recapitulate the hypothesized objective reaction of precursor biomass synthesis with a SSE _S = 4.210 × 10^-4 when the reaction was included in the network stoichiometry but its experimental flux was removed from the available flux data.