Statistics of optimal information flow in ensembles of regulatory motifs

Genetic regulatory circuits universally cope with different sources of noise that limit their ability to coordinate input and output signals. In many cases, optimal regulatory performance can be thought to correspond to configurations of variables and parameters that maximize the mutual information between inputs and outputs. Since the mid-2000s, such optima have been well characterized in several biologically relevant cases. Here we use methods of statistical field theory to calculate the statistics of the maximal mutual information (the "capacity") achievable by tuning the input variable only in an ensemble of regulatory motifs, such that a single controller regulates N targets. Assuming (i) sufficiently large N, (ii) quenched random kinetic parameters, and (iii) small noise affecting the input-output channels, we can accurately reproduce numerical simulations both for the mean capacity and for the whole distribution. Our results provide insight into the inherent variability in effectiveness occurring in regulatory systems with heterogeneous kinetic parameters.