Schematic illustrating the integration of exometabolomic (EM) data with the constraint-based framework. (A) Cells are subjected to genetic and/or environmental perturbations to secrete metabolite patterns unique to that condition. (B) EM is detected, identified, and quantified. (C) EM data is integrated as required secretion flux constraints to define allowable solution space. (D) Random sampling of solution space yields the range of feasible flux distributions for intracellular reactions. (E) Sampled fluxes were compared to sampled fluxes of another condition to determine which metabolic regions were altered between the two conditions (see Figure 2). (F) Significantly altered metabolic regions were identified.