Efficient Manipulation and Generation of Kirchhoff Polynomials for the Analysis of Non-equilibrium Biochemical Reaction Networks

Abstract

Kirchhoff polynomials are central for deriving symbolic steady-state expressions of models whose dynamics are governed by linear diffusion on graphs. In biology, such models have been unified under a common linear framework subsuming studies across areas such as enzyme kinetics, G-protein coupled receptors, ion channels, and gene regulation. Due to "history dependence" away from thermodynamic equilibrium these models suffer from a (super) exponential growth in the size of their symbolic steady-state expressions and respectively Kirchhoff polynomials. This algebraic explosion has limited applications of the linear framework. However, recent results on the graph-based prime factorisation of Kirchhoff polynomials may help subdue the combinatorial complexity. By prime decomposing the graphs contained in an expression of Kirchhoff polynomials and identifying the graphs giving rise to equal polynomials, we formulate a coarse-grained variant of the expression suitable for symbolic simplification. We devise criteria to efficiently test the equality of Kirchhoff polynomials and propose two heuristic algorithms to explicitly generate individual Kirchhoff polynomials in a compressed form; they are inspired by algebraic simplifications but operate on the corresponding graphs. We illustrate the practicality of the developed theory and algorithms for a diverse set of graphs of different sizes and for non-equilibrium gene regulation analyses.