Asymptotology of Chemical Reaction Networks

The concept of the limiting step is extended to the asymptotology of multiscale reaction networks. Complete theory for linear networks with well separated reaction rate constants is developed. We present algorithms for explicit approximations of eigenvalues and eigenvectors of kinetic matrix. Accuracy of estimates is proven. Performance of the algorithms is demonstrated on simple examples. Application of algorithms to nonlinear systems is discussed.Comment: 23 pages, 8 figures, 84 refs, Corrected Journal Versio

On the performance of nonlinear dynamical systems under parameter perturbation

AbstractWe present a method for analysing the deviation in transient behaviour between two parameterised families of nonlinear ODEs, as initial conditions and parameters are varied within compact sets over which stability is guaranteed. This deviation is taken to be the integral over time of a user-specified, positive definite function of the difference between the trajectories, for instance the L2 norm. We use sum-of-squares programming to obtain two polynomials, which take as inputs the (possibly differing) initial conditions and parameters of the two families of ODEs, and output upper and lower bounds to this transient deviation. Equality can be achieved using symbolic methods in a special case involving Linear Time Invariant Parameter Dependent systems. We demonstrate the utility of the proposed methods in the problems of model discrimination, and location of worst case parameter perturbation for a single parameterised family of ODE models

Analysis of Biochemical Reaction Networks using Tropical and Polyhedral Geometry Methods

The field of systems biology makes an attempt to realise various biological functions and processes as the emergent properties of the underlying biochemical network model. The area of computational systems biology deals with the computational methods to compute such properties. In this context, the thesis primarily discusses novel computational methods to compute the emergent properties as well as to recognize the essence in complex network models. The computational methods described in the thesis are based on the computer algebra techniques, namely tropical geometry and extreme currents. Tropical geometry is based on ideas of dominance of monomials appearing in a system of differential equations, which are often used to describe the dynamics of the network model. In such differential equation based models, tropical geometry deals with identification of the metastable regimes, defined as low dimensional regions of the phase space close to which the dynamics is much slower compared to the rest of the phase space. The application of such properties in model reduction and symbolic dynamics are demonstrated in the network models obtained from a public database namely Biomodels. Extreme currents are limiting edges of the convex polyhedrons describing the admissible fluxes in biochemical networks, which are helpful to decompose a biochemical network into a set of irreducible pathways. The pathways are shown to be associated with given clinical outcomes thereby providing some mechanistic insights associated with the clinical phenotypes. Similar to the tropical geometry, the method based on extreme currents is evaluated on the network models derived from a public database namely KEGG. Therefore, this thesis makes an attempt to explain the emergent properties of the network model by determining extreme currents or metastable regimes. Additionally, their applicability in the real world network models are discussed

Algebraic Aspects of (Bio) Nano-chemical Reaction Networks and Bifurcations in Various Dynamical Systems

The dynamics of (bio) chemical reaction networks have been studied by different methods. Among these methods, the chemical reaction network theory has been proven to successfully predicate important qualitative properties, such as the existence of the steady state and the asymptotic behavior of the steady state. However, a constructive approach to the steady state locus has not been presented. In this thesis, with the help of toric geometry, we propose a generic strategy towards this question. This theory is applied to (bio)nano particle configurations. We also investigate Hopf bifurcation surfaces of various dynamical systems

Some Exact Results for the Exclusion Process

The asymmetric simple exclusion process (ASEP) is a paradigm for non-equilibrium physics that appears as a building block to model various low-dimensional transport phenomena, ranging from intracellular traffic to quantum dots. We review some recent results obtained for the system on a periodic ring by using the Bethe Ansatz. We show that this method allows to derive analytically many properties of the dynamics of the model such as the spectral gap and the generating function of the current. We also discuss the solution of a generalized exclusion process with $N$-species of particles and explain how a geometric construction inspired from queuing theory sheds light on the Matrix Product Representation technique that has been very fruitful to derive exact results for the ASEP.Comment: 21 pages; Proceedings of STATPHYS24 (Cairns, Australia, July 2010

Robust simplifications of multiscale biochemical networks

<p>Abstract</p> <p>Background</p> <p>Cellular processes such as metabolism, decision making in development and differentiation, signalling, etc., can be modeled as large networks of biochemical reactions. In order to understand the functioning of these systems, there is a strong need for general model reduction techniques allowing to simplify models without loosing their main properties. In systems biology we also need to compare models or to couple them as parts of larger models. In these situations reduction to a common level of complexity is needed.</p> <p>Results</p> <p>We propose a systematic treatment of model reduction of multiscale biochemical networks. First, we consider linear kinetic models, which appear as "pseudo-monomolecular" subsystems of multiscale nonlinear reaction networks. For such linear models, we propose a reduction algorithm which is based on a generalized theory of the limiting step that we have developed in <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Second, for non-linear systems we develop an algorithm based on dominant solutions of quasi-stationarity equations. For oscillating systems, quasi-stationarity and averaging are combined to eliminate time scales much faster and much slower than the period of the oscillations. In all cases, we obtain robust simplifications and also identify the critical parameters of the model. The methods are demonstrated for simple examples and for a more complex model of NF-<it>κ</it>B pathway.</p> <p>Conclusion</p> <p>Our approach allows critical parameter identification and produces hierarchies of models. Hierarchical modeling is important in "middle-out" approaches when there is need to zoom in and out several levels of complexity. Critical parameter identification is an important issue in systems biology with potential applications to biological control and therapeutics. Our approach also deals naturally with the presence of multiple time scales, which is a general property of systems biology models.</p