Section 2.3 is devoted to exploring the distribution of essentiality classes and established topological categories across three-node subgraphs of the reaction-centric metabolic network. In Section 4 we interpret the findings from Section 2.2 and Section 2.3 and use them to topologically characterize a typical reaction displaying medium-dependent essentiality. See Table 1 for a summary
of model, reaction category, activity, and essentiality statistics. Table 1 Summarizing statistics of reaction categories and essentialities. 2. Results 2.1. Relative Essentiality Analysis In order to subdivide the metabolic reactions into essentiality Inhibitors,research,lifescience,medical classes, namely non-essential, conditional lethal, and essential, we quantify the relative essentiality of a reaction by computing optimal, i.e., maximizing biomass production, learn more steady-state flux distributions for over more than 7 × 104 combinatorial minimal media conditions. Furthermore, all subsequent single reaction knockouts of active (non-zero flux carrying) reactions are performed to identify for each medium Inhibitors,research,lifescience,medical condition
the set of essential reactions (see Methods for details). An illustrative example of this concept, involving E. coli central carbon metabolism Inhibitors,research,lifescience,medical [31], is provided in the supplementary materials. The relative essentiality of a particular reaction is then defined as the number of lethal outcomes due to its removal divided by the number of environmental conditions under which it has been active. An alternative definition of relative essentiality would be to normalize the number of lethal outcomes to the total number of media sampled. In this case, however, essential reactions that Inhibitors,research,lifescience,medical are rarely active would
give an unrealistically low essentiality value. Figure 2a shows the sorted relative essentiality profile of all reactions in the E. coli model, which have been active at least once during the FBA simulations; blocked reactions [32] have thus been eliminated; see also Methods). In Figure 2a the three essentiality classes Inhibitors,research,lifescience,medical are clearly visible: The removal of most reactions has no or only small consequences for the production of biomass (non-essential). Some reactions are globally essential (essential) and a third set is only medium-dependent essential (conditional lethal). Excluding non-essential reactions, Figure 2b depicts the relative essentiality profile in a semilog plot. The stepwise appearance of the conditional Phosphoprotein phosphatase lethal curve indicates three major groups of reactions that exhibit very similar relative essentiality scores, connected by some intermediate reactions. Figure 2 Outcome of combinatorial minimal media simulations. (a) Sorted relative essentiality profile determined by the simulation of reaction deletions under 72468 combinatorial minimal media conditions. The three different essentiality classes are indicated … Almaas et al. [21] reported a high, global essentiality for MC reactions. This finding suggests a higher essentiality for more active reactions.
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