Reduction of chemical reaction networks with approximate conservation laws

Model reduction of fast-slow chemical reaction networks based on the quasi-steady state approximation fails when the fast subsystem has first integrals. We call these first integrals approximate conservation laws. In order to define fast subsystems and identify approximate conservation laws, we use ideas from tropical geometry. We prove that any approximate conservation law evolves more slowly than all the species involved in it and therefore represents a supplementary slow variable in an extended system. By elimination of some variables of the extended system, we obtain networks without approximate conservation laws, which can be reduced by standard singular perturbation methods. The field of applications of approximate conservation laws covers the quasi-equilibrium approximation, which is well known in biochemistry. We discuss reductions of slow-fast as well as multiple timescale systems. Networks with multiple timescales have hierarchical relaxation. At a given timescale, our multiple timescale reduction method defines three subsystems composed of (i) slaved fast variables satisfying algebraic equations, (ii) slow driving variables satisfying reduced ordinary differential equations, and (iii) quenched much slower variables that are constant. The algebraic equations satisfied by fast variables define chains of nested normally hyperbolic invariant manifolds. In such chains, faster manifolds are of higher dimension and contain the slower manifolds. Our reduction methods are introduced algorithmically for networks with monomial reaction rates and linear, monomial, or polynomial approximate conservation laws. We propose symbolic algorithms to reshape and rescale the networks such that geometric singular perturbation theory can be applied to them, test the applicability of the theory, and finally reduce the networks. As a proof of concept, we apply this method to a model of the TGF-beta signaling pathway

On Defining and Computing ``Good'' Conservation Laws

International audienceConservation laws are a key-tool to study systems of chemical reactions in biology. We address the problem of defining and computing "good" sets of conservation laws. In this article, we chose to focus on sparsest sets of conservation laws. We present a greedy algorithm computing a sparsest set of conservation laws equivalent to a given set of conservation laws. Benchmarks over a subset of the curated models taken from the BioModels database are given