Estimating the size of the solution space of metabolic networks

In this work we propose a novel algorithmic strategy that allows for an efficient characterization of the whole set of stable fluxes compatible with the metabolic constraints. The algorithm, based on the well-known Bethe approximation, allows the computation in polynomial time of the volume of a non full-dimensional convex polytope in high dimensions. The result of our algorithm match closely the prediction of Monte Carlo based estimations of the flux distributions of the Red Blood Cell metabolic network but in incomparably shorter time. We also analyze the statistical properties of the average fluxes of the reactions in the E-Coli metabolic network and finally to test the effect of gene knock-outs on the size of the solution space of the E-Coli central metabolism.Comment: 8 pages, 7 pdf figure

A Statistical Theory of Designed Quantum Transport Across Disordered Networks

We explain how centrosymmetry, together with a dominant doublet in the local density of states, can guarantee interference-assisted, strongly enhanced, strictly coherent quantum excitation transport between two predefined sites of a random network of two-level systems. Starting from a generalisation of the chaos assisted tunnelling mechanism, we formulate a random matrix theoretical framework for the analytical prediction of the transfer time distribution, of lower bounds of the transfer efficiency, and of the scaling behaviour of characteristic statistical properties with the size of the network.Comment: 23 pages, 8 figure

Characterizing steady states of genome-scale metabolic networks in continuous cell cultures

We present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. We provide a method to determine the steady states of this system that is tractable for metabolic networks of arbitrary complexity. We demonstrate our approach in a toy model first, and then in a genome-scale metabolic network of the Chinese hamster ovary cell line, obtaining results that are in qualitative agreement with experimental observations. More importantly, we derive a number of consequences from the model that are independent of parameter values. First, that the ratio between cell density and dilution rate is an ideal control parameter to fix a steady state with desired metabolic properties invariant across perfusion systems. This conclusion is robust even in the presence of multi-stability, which is explained in our model by the negative feedback loop on cell growth due to toxic byproduct accumulation. Moreover, a complex landscape of steady states in continuous cell culture emerges from our simulations, including multiple metabolic switches, which also explain why cell-line and media benchmarks carried out in batch culture cannot be extrapolated to perfusion. On the other hand, we predict invariance laws between continuous cell cultures with different parameters. A practical consequence is that the chemostat is an ideal experimental model for large-scale high-density perfusion cultures, where the complex landscape of metabolic transitions is faithfully reproduced. Thus, in order to actually reflect the expected behavior in perfusion, performance benchmarks of cell-lines and culture media should be carried out in a chemostat

Gauge-free cluster variational method by maximal messages and moment matching

We present an implementation of the cluster variational method (CVM) as a message passing algorithm. The kind of message passing algorithm used for CVM, usually named generalized belief propagation (GBP), is a generalization of the belief propagation algorithm in the same way that CVM is a generalization of the Bethe approximation for estimating the partition function. However, the connection between fixed points of GBP and the extremal points of the CVM free energy is usually not a one-to-one correspondence because of the existence of a gauge transformation involving the GBP messages. Our contribution is twofold. First, we propose a way of defining messages (fields) in a generic CVM approximation, such that messages arrive on a given region from all its ancestors, and not only from its direct parents, as in the standard parent-to-child GBP. We call this approach maximal messages. Second, we focus on the case of binary variables, reinterpreting the messages as fields enforcing the consistency between the moments of the local (marginal) probability distributions. We provide a precise rule to enforce all consistencies, avoiding any redundancy, that would otherwise lead to a gauge transformation on the messages. This moment matching method is gauge free, i.e., it guarantees that the resulting GBP is not gauge invariant. We apply our maximal messages and moment matching GBP to obtain an analytical expression for the critical temperature of the Ising model in general dimensions at the level of plaquette CVM. The values obtained outperform Bethe estimates, and are comparable with loop corrected belief propagation equations. The method allows for a straightforward generalization to disordered systems