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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,…
Despite major environmental and genetic differences, microbial metabolic networks are known to generate consistent physiological outcomes across vastly different organisms. This remarkable robustness suggests that, at least in bacteria,…
The analysis of non-equilibrium steady states of biochemical reaction networks relies on finding the configurations of fluxes and chemical potentials satisfying stoichiometric (mass balance) and thermodynamic (energy balance) constraints.…
Cells adapt their metabolic fluxes in response to changes in the environment. We present a framework for the systematic construction of flux-based graphs derived from organism-wide metabolic networks. Our graphs encode the directionality of…
Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to…
Biological systems are governed by coupled interactions between intracellular metabolism and bioreactor operation that span multiple time scales. Constraint-based metabolic models are widely used to describe intracellular metabolism, but…
The major biochemical networks of the living cell, the network of interacting genes and the network of biochemical reactions, are highly interdependent, however, they have been studied mostly as separate systems so far. In the last years an…
Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain metabolic enzymes. The necessary enzyme amount per unit flux is a major determinant of metabolic strategies both in evolution and…
We outline a modeling and optimization strategy for investigating dynamic metabolic engineering interventions. Our framework is particularly useful at the early stages of research and development, often constrained by limited knowledge and…
Current mathematical frameworks for predicting the flux state and macromolecular composition of the cell do not rely on thermodynamic constraints to determine the spontaneous direction of reactions. These predictions may be biologically…
We propose a new scheme to infer the metabolic fluxes of cell cultures in a chemostat. Our approach is based on the Maximum Entropy Principle and exploits the understanding of the chemostat dynamics and its connection with the actual…
Optimization-based models have been used to predict cellular behavior for over 25 years. The constraints in these models are derived from genome annotations, measured macro-molecular composition of cells, and by measuring the cell's growth…
We cast the metabolism of interacting cells within a statistical mechanics framework considering both, the actual phenotypic capacities of each cell and its interaction with its neighbors. Reaction fluxes will be the components of…
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…
Elementary flux modes (EFMs) are pathways through a metabolic reaction network that connect external substrates to products. Using EFMs, a metabolic network can be transformed into its macroscopic counterpart, in which the internal…
We consider the problem of inferring the probability distribution of flux configurations in metabolic network models from empirical flux data. For the simple case in which experimental averages are to be retrieved, data are described by a…
Quite generally, constraint-based metabolic flux analysis describes the space of viable flux configurations for a metabolic network as a high-dimensional polytope defined by the linear constraints that enforce the balancing of production…
In this thesis, we have studied the large scale structure and system level dynamics of certain biological networks using tools from graph theory, computational biology and dynamical systems. We study the structure and dynamics of large…
In this work maximum entropy distributions in the space of steady states of metabolic networks are defined upon constraining the first and second moment of the growth rate. Inherent bistability of fast and slow phenotypes, akin to a Van-Der…
We examine the modular structure of the metabolic network when combined with the regulatory network representing direct regulation of enzymes by small metabolites in E.coli. In order to identify the modular structure we introduce clustering…