Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Role of noise and parametric variation in the dynamics of gene regulatory circuits

Preprint

Read this article at

ScienceOpenPublisher
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Stochasticity in gene expression impacts the dynamics and functions of gene regulatory circuits. Intrinsic noises, including those that are caused by low copy number of molecules and transcriptional bursting, are usually studied by stochastic analysis methods, such as Gillespie algorithm and Langevin simulation. However, the role of extrinsic factors, such as cell-to-cell variability and heterogeneity in the microenvironment, is still elusive. To evaluate the effects of both intrinsic and extrinsic noises, we develop a new method, named sRACIPE, by integrating stochastic analysis with random circuit perturbation (RACIPE) method. Unlike traditional methods, RACIPE generates and analyzes an ensemble of mathematical models with random kinetic parameters. Previously, we have shown that the gene expression from random models form robust and functionally related clusters. Under the framework of this randomization-based approach, here we develop two stochastic simulation schemes, aiming to reduce the computational cost without sacrificing the convergence of statistics. One scheme uses constant noise to capture the basins of attraction, and the other one uses simulated annealing to detect the stability of states. By testing the methods on several gene regulatory circuits, we found that high noise, but not large parameter variation, merges clusters together. Our approach quantifies the robustness of a gene circuit in the presence of noise and sheds light on a new mechanism of noise-induced hybrid states. We have implemented sRACIPE into a freely available R package.

      Related collections

      Author and article information

      Journal
      bioRxiv
      March 28 2018
      10.1101/291153
      © 2018
      Product

      Quantitative & Systems biology

      Comments

      Comment on this article