Linear noise approximation of noise-induced oscillation in NF-{\kappa}B signaling network

TL;DR

This paper develops an analytical framework using the linear noise approximation to understand noise-induced oscillations in the NF-κB signaling network, revealing the physical mechanisms behind stochastic oscillatory behavior.

Contribution

It introduces a novel analytical approach based on the master equation and van Kampen's expansion to analyze noise-induced oscillations in NF-κB signaling.

Findings

Identified noise-induced oscillatory regimes in NF-κB signaling.

Constructed phase diagram showing parameter regions with oscillations.

Provided insights into the physical mechanisms of stochastic oscillations.

Abstract

NF-{\kappa}B, one of key regulators of inflammation, apoptosis, and differentiation, was found to have noisy oscillatory shuttling between the nucleus and the cytoplasm in single cells when cells are stimulated by cytokine TNF{\alpha}. We present the analytical analysis which uncovers the underlying physical mechanisms of this spectacular noise-induced transition in biological networks. Starting with the master equation describing both signaling and transcription events in NF-{\kappa}B signaling network, we derived the macroscopic and the Fokker-Planck equations by using van Kampen's sysem size expansion. Using the noise-induced oscillatory signatures present in the power spectrum, we constructed the two-dimensional phase diagram where the noise-induced oscillation emerges in the dynamically stable parameter space.