Stochastic fluctuations can reveal the feedback signs of gene regulatory networks at the single-molecule level

Sci Rep. 2017 Nov 22;7(1):16037. doi: 10.1038/s41598-017-15464-9.

Abstract

Understanding the relationship between spontaneous stochastic fluctuations and the topology of the underlying gene regulatory network is of fundamental importance for the study of single-cell stochastic gene expression. Here by solving the analytical steady-state distribution of the protein copy number in a general kinetic model of stochastic gene expression with nonlinear feedback regulation, we reveal the relationship between stochastic fluctuations and feedback topology at the single-molecule level, which provides novel insights into how and to what extent a feedback loop can enhance or suppress molecular fluctuations. Based on such relationship, we also develop an effective method to extract the topological information of a gene regulatory network from single-cell gene expression data. The theory is demonstrated by numerical simulations and, more importantly, validated quantitatively by single-cell data analysis of a synthetic gene circuit integrated in human kidney cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Regulatory Networks / genetics*
  • Humans
  • Models, Genetic
  • Stochastic Processes