The large number of ways in which this can be done is a manifestation of the combinatorial explosion, and demonstrates that the bow-tie splitting will substantially reduce the computational effort of calculating EMs and the resulting

MCSs. More explicitly, the reactions constituting MCSs of a whole network can be classified in terms of the blocked reactions’ locations in the bow-tie decomposition: (1) All substrate reactions (S subnet) plus GSC reactions blocking any cyclic EMs that could take place Inhibitors,research,lifescience,medical without inputs from the substrate reactions. In this case, no product reactions (P subnet) need blocking; (2) All product reactions(P subnet) plus GSC reactions blocking the cyclic EMs- in this case no

substrate (S subnet) need to be blocked; (3) All GSC reactions that connect the S to the P subnet. No substrate or product reactions need to be blocked; (4) A combination of S reactions plus GSC Inhibitors,research,lifescience,medical reactions reached from the unblocked S reactions. P reactions don’t need to be blocked; (5) A combination of P reactions plus GSC reactions that could reach the Inhibitors,research,lifescience,medical unblocked P reactions. S reactions don’t need blocking. These classifications can be used to investigate the question of whether a bow-tie decomposition can be derived from a known MCSs table. For example, a plausible strategy to identify GSC reactions is as follows: From all MCS, eliminate any that involve reactions that are known to belong to S or P; Order the remainder by increasing size and/or decreasing mean fragility coefficient; Choose a cutoff value in this sequence, and allocate all reactions that belong to MCSs in the top section of the sequence to the GSC. If the bow-tie structure is pronounced, Inhibitors,research,lifescience,medical there should be a clear separation between the small, high fragility coefficient MCSs that belong to the GSC and the rest, otherwise the choice of a cutoff may be problematic. An MCS analysis may be helpful to examine

if a bow-tie structure exists and partially detect members of its main components, but not to make a full partitioning. Noting Inhibitors,research,lifescience,medical that bow-ties can assist with combinatorial explosion by decomposing large networks into subnets that can be analyzed by MCSs and EMs, we conclude that despite some overlap in the concepts and applications Mannose-binding protein-associated serine protease of bow-ties and MCSs, there is no clear cut correspondence between the two network descriptions. While bow-ties try to extract subsets of nodes that are of importance in the metabolic network, the EM and MCS approaches focus on comprehensive sets that are in different ways essential. Moreover, EMs are, by construction, the “constituents” of a steady metabolic state. So they, and MCSs, reflect the stoichiometry Alectinib cost underlying the network and describe the metabolism, not just the topology of the network. In this respect, MCS (and EM) analysis is more powerful than bow-ties that just characterize network topology. 5.3.