Localization of Noise in Biochemical Networks

Abstract

Noise, or uncertainty in biochemical networks, has become an important aspect of many biological problems. Noise can arise and propagate from external factors and probabilistic chemical reactions occurring in small cellular compartments. For species survival, it is important to regulate such uncertainties in executing vital cell functions. Regulated noise can improve adaptability, whereas uncontrolled noise can cause diseases. Simulation can provide a detailed analysis of uncertainties, but parameters such as rate constants and initial conditions are usually unknown. A general understanding of noise dynamics from the perspective of network structure is highly desirable. In this study, we extended the previously developed law of localization for characterizing noise in terms of (co)variances and developed noise localization theory. With linear noise approximation, we can expand a biochemical network into an extended set of differential equations representing a fictitious network for pseudo-components consisting of variances and covariances, together with chemical species. Through localization analysis, perturbation responses at the steady state of pseudo-components can be summarized into a sensitivity matrix that only requires knowledge of network topology. Our work allows identification of buffering structures at the level of species, variances, and covariances and can provide insights into noise flow under non-steady-state conditions in the form of a pseudo-chemical reaction. We tested noise localization in various systems, and here we discuss its implications and potential applications. Results show that this theory is potentially applicable in discriminating models, scanning network topologies with interesting noise behavior, and designing and perturbing networks with the desired response.

Noise response in monomolecular closed systems

“…[30] SSA had also been extended in structural bifurcation analysis [31] and fluxaugmented bifurcation analysis. [32] In recent work, [33] we extended the SSA [28] and linear noise approximation (LNA) for noise response inference in terms of changes in variances and covariances, with a focus on open systems. This current work covers monomolecular closed systems without reactant splitting or autocatalysis which are mathematically easier to handle, as solutions to their CME exist.…”