The novelty of the BOSS optimization framework. Panel (a) depicts a simple system comprised of three components and five reactions, including an objective reaction robj denoted in red. Assuming a stoichiometric network reconstruction of this system (i.e., based on available literature) includes all three components and four of five reactions, excluding the objective reaction, panels (b) and (c) illustrate the objective functions that may be inferred by ObjFind and BOSS, respectively. Specifically, panel (b) shows how ObjFind generates a set of weightings, termed coefficients of importance (CoIs), on the reactions within the network. In this case, with the actual objective not in the stoichiometric reconstruction, ObjFind fails to assign a CoI to robj. By contrast, panel (c) shows how BOSS generates a de novo stoichiometric reaction and recapitulates the actual system objective regardless of whether the actual objective is included as part of the stoichiometric reconstruction.