Functional redundancy in the NF-κB signalling pathway

Abstract: The ability to represent intracellular biochemical dynamics via deterministic and stochastic modelling is one of the crucial components to move biological sciences in the observe-predict-control-design knowledge ladder. Compared to the engineering or physics problems, dynamical models in quantitative biology typically dependent on a relatively large number of parameters. Therefore, the relationship between model parameters and dynamics is often prohibitively difficult to determine. We developed a method to depict the input-output relationship for multi-parametric stochastic and deterministic models via information-theoretic quantification of similarity between model parameters and modules. Identification of most information-theoretically orthogonal biological components, provided mathematical language to precisely communicate and visualise compensation like phenomena such as biological robustness, sloppiness and statistical non-identifiability. A comprehensive analysis of the multi-parameter NF-$\kappa$B signalling pathway demonstrates that the information-theoretic similarity reflects a topological structure of the network. Examination of the currently available experimental data on this system reveals the number of identifiable parameters and suggests informative experimental protocols.