engleski

Synergy Analysis in Reaction Systems

This work introduces the concept of analysis of synergy interactions in chemical (biochemical) reaction systems. The systems are defined by mass balances for reacting species, reaction network is given by a stoichiometric matrix, reaction (kinetic) parameters, and parameters of interaction between the reaction system and it’ s surrounding. Systems analysis is based on statistical evaluation of numerical results of computer simu-lation of effects of a set of uncorrelated stochastic parameters, defined by corresponding ranges and probability distributions. From the simulation data are extracted parameter global sensitivities and synergy effects of each parameter in interaction with the whole system. The global parameter sensitivities are defined as ratios of con-ditional variances of expected values for each parameter and the total dispersion of simulation data. The syn-ergy effects are defined as the relative difference between expected values of the conditional variances with ex-clusion of each parameter and the variance of the conditional expected value of the parameter. Numerical evaluations are performed by use of sampling the parametric space by Lissajous type of curves and the Fourier Amplitude Sensitivity Test (FAST) algorithm. The method is applied for analysis of propagation of hepatitis B virus (HBV) in a stochastic single cell model, and for metabolic control analysis of a branched network. The re-sults for virus propagation show dominant synergy effect of the system parameters, compared to negligible in-fluence of individual parameters. The metabolic control analysis show that under homeostatic conditions influ-ence of the individual enzymes is dominant and the key enzyme responsible for flux regulation is determined. However, under perturbed homeostatic conditions influence of synergy effects dominates over impact of indi-vidual parameters. Applicability of the proposed concept is discussed in view of model improvement and po-tential control of reaction systems.

reaction system, synergy, global parameter sensitivity, HBV, MCA, FAST

nije evidentirano