Framework of the FVSEOF with GR constraints for identifying gene amplification targets that enhance the production of a target product. The FVSEOF method scans the changes in the metabolic flux variabilities in response to an enhanced flux toward a target product. The method then selects amplification target reactions, the fluxes of which increase in response to the forced increase in the flux toward the target bioproduct. ( A) During the FVSEOF implementation, three types of intracellular flux profiles are typically identified: increased, decreased, or unchanged, but oscillatory flux profiles can also be found in some cases. ( B) To evaluate the gene amplification candidates, the slope ( qslope) was calculated based on a linear regression between the enforced production rate of a target product and the Vavg values of the candidate reactions. The positive correlation in the slope indicates that the corresponding reaction may be a gene amplification candidate. On the basis of the qslope values, we considered the sensitivities of the identified gene amplification candidates to the enforced production of a target chemical. A large value of qslope indicates that the corresponding reaction may be more sensitive to the enforced production of a target chemical, than reactions with smaller qslope values.
Park et al. BMC Systems Biology 2012 6:106 doi:10.1186/1752-0509-6-106