Understanding Cellular Noise with Optical Perturbation and Deep Learning

TL;DR

This paper presents an optically-controlled perturbation system combined with deep learning to precisely modulate and quantify cellular noise, advancing understanding of gene expression and biochemical dynamics.

Contribution

It introduces a novel light-sensitive perturbation platform and a deep neural network model for accurate rate constant estimation in cellular noise analysis.

Findings

System exhibits high sensitivity to pulsed light signals.

Deep neural network accurately maps rate constants to system dynamics.

Optical control effectively modulates molecular expression and noise levels.

Abstract

Noise plays a crucial role in the regulation of cellular and organismal function and behavior. Exploring noise's impact is key to understanding fundamental biological processes, such as gene expression, signal transduction, and the mechanisms of development and evolution. Currently, a comprehensive method to quantify dynamical behavior of cellular noise within these biochemical systems is lacking. In this study, we introduce an optically-controlled perturbation system utilizing the light-sensitive Phytochrome B (PhyB) from \textit{Arabidopsis thaliana}, which enables precise noise modulation with high spatial-temporal resolution. Our system exhibits exceptional sensitivity to light, reacting consistently to pulsed light signals, distinguishing it from other photoreceptor-based promoter systems that respond to a single light wavelength. To characterize our system, we developed a stochastic model for phytochromes that accounts for photoactivation/deactivation, thermal reversion, and the dynamics of the light-activated gene promoter system. To precisely control our system, we determined the rate constants for this model using an omniscient deep neural network that can directly map rate constant combinations to time-dependent state joint distributions. By adjusting the activation rates through light intensity and degradation rates via N-terminal mutagenesis, we illustrate that out optical-controlled perturbation can effectively modulate molecular expression level as well as noise. Our results highlight the potential of employing an optically-controlled gene perturbation system as a noise-controlled stimulus source. This approach, when combined with the analytical capabilities of a sophisticated deep neural network, enables the accurate estimation of rate constants from observational data in a broad range of biochemical reaction networks.