Dispersion for two classes of random variables: General theory and application to inference of an external ligand concentration by a cell

We derive expressions for the dispersion for two classes of random variables in Markov processes. Random variables such as current and activity pertain to the first class, which is composed of random variables that change whenever a jump in the stochastic trajectory occurs. The second class corresponds to the time the trajectory spends in a state (or cluster of states). While the expression for the first class follows straightforwardly from known results in the literature, we show that a similar formalism can be used to derive an expression for the second class. As an application, we use this formalism to analyze a cellular two-component network estimating an external ligand concentration. The uncertainty related to this external concentration is calculated by monitoring different random variables related to an internal protein. We show that, inter alia, monitoring the time spent in the phosphorylated state of the protein leads to a finite uncertainty only if there is dissipation, whereas the uncertainty obtained from the activity of the transitions of the internal protein can reach the Berg-Purcell limit even in equilibrium.