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Characterizing the capabilities, criticalities and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of the potential damage of single enzymopathies. Sampling the space of optimal flux states in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.
The response to a knockout of a node is a characteristic feature of a networked dynamical system. Knockout resilience in the dynamics of the remaining nodes is a sign of robustness. Here we study the effect of knockouts for binary state sequences and
The metabolic network of a living cell involves several hundreds or thousands of interconnected biochemical reactions. Previous research has shown that under realistic conditions only a fraction of these reactions is concurrently active in any given
Understanding the system level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches such as the constraint-based flux balance analyses (FBA) have
Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this b
We study a simplified, solvable model of a fully-connected metabolic network with constrained quenched disorder to mimic the conservation laws imposed by stoichiometry on chemical reactions. Within a spin-glass type of approach, we show that in prese