Speeding Up the Structural Analysis of Metabolic Network Models Using the Fredman-Khachiyan Algorithm B.

The problem of computing the Elementary Flux Modes (EFMs) and Minimal Cut Sets (MCSs) of metabolic network is a fundamental one in metabolic networks. A key insight is that they can be understood as a dual pair of monotone Boolean functions (MBFs). Using this insight, this computation reduces to the question of generating from an oracle a dual pair of MBFs. If one of the two sets (functions) is known, then the other can be computed through a process known as dualization. Fredman and Khachiyan provided two algorithms, which they called simply A and B that can serve as an engine for oracle-based generation or dualization of MBFs. We look at efficiencies available in implementing their algorithm B, which we will refer to as FK -B. Like their algorithm A, FK -B certifies whether two given MBFs in the form of Conjunctive Normal Form and Disjunctive Normal Form are dual or not, and in case of not being dual it returns a conflicting assignment (CA), that is, an assignment that makes one of the given Boolean functions True and the other one False . The FK -B algorithm is a recursive algorithm that searches through the tree of assignments to find a CA. If it does not find any CA, it means that the given Boolean functions are dual. In this article, we propose six techniques applicable to the FK -B and hence to the dualization process. Although these techniques do not reduce the time complexity, they considerably reduce the running time in practice. We evaluate the proposed improvements by applying them to compute the MCSs from the EFMs in the 19 small- and medium-sized models from the BioModels database along with 4 models of biomass synthesis in Escherichia coli that were used in an earlier computational survey Haus et al. (2008).