We present a stochastic framework to study signal transmission in a generic two-step cascade S→X→Y. Starting from a set of Langevin equations obeying Gaussian noise processes we calculate the variance and covariance while considering both linear and nonlinear production terms for different biochemical species of the cascade. These quantities are then used to calculate the net synergy within the purview of partial information decomposition. We show that redundancy in information transmission is essentially an important consequence of Markovian property of the two-step cascade motif. We also show that redundancy increases fidelity of the signaling pathway.
Using the formalism of information theory, we analyze the mechanism of information transduction in a simple one-step signaling cascade S→X representing the gene regulatory network.Approximating the signaling channel to be Gaussian, we describe the dynamics using Langevin equations. Upon discretization, we calculate the associated second moments for linear and nonlinear regulation of the output by the input, which follows the birth-death process. While mutual information between the input and the output characterizes the channel capacity, the Fano factor of the output gives a clear idea of how internal and external fluctuations assemble at the output level. To quantify the contribution of the present state of the input to predict the future output, transfer entropy is computed. We find that higher amount of transfer entropy is accompanied by the greater magnitude of external fluctuations (quantified by the Fano factor of the output) propagation from the input to the output. We notice that low input population characterized by the number of signaling molecules S, which fluctuates in a relatively slower fashion compared to its downstream (target) species X, is maximally able to predict (as quantified by transfer entropy) the future state of the output. Our computations also reveal that with increased linear nature of the input-output interaction, all three metrics of mutual information, Fano factor and, transfer entropy achieve relatively larger magnitudes. *
We present an information-theoretic formalism to study signal transduction in four architectural variants of a model two-step cascade with increasing input population. Our results categorize these four types into two classes depending upon the effect of activation and repression on mutual information, net synergy, and signal-to-noise ratio. Using the Gaussian framework and linear noise approximation, we derive the analytic expressions for these metrics to establish their underlying relationships in terms of the biochemical parameters. We also verify our approximations through stochastic simulations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.