Modeling and Simulation of Genetic Regulatory Systems: A Literature Review

  title={Modeling and Simulation of Genetic Regulatory Systems: A Literature Review},
  author={Hidde de Jong},
  journal={J. Comput. Biol.},
In order to understand the functioning of organisms on the molecular level, we need to know which genes are expressed, when and where in the organism, and to which extent. The regulation of gene expression is achieved through genetic regulatory systems structured by networks of interactions between DNA, RNA, proteins, and small molecules. As most genetic regulatory networks of interest involve many components connected through interlocking positive and negative feedback loops, an intuitive… 

Qualitative Modeling and Simulation of Genetic Regulatory Networks : From Piecewise-Affine Differential Equations to Reporter Gene Data ( and Back )

The functioning and development of living organisms is controlled by large and complex networks of genes, proteins, small molecules, and their interactions, so-called genetic regulatory networks. The

Modeling and Simulation of Genetic Regulatory Networks

This tutorial reviews the two principal approaches used in the analysis of genetic regulatory networks: methods based on differential equation models and stochastic models and indicates some alternative methods that have emerged in response to the difficulties encountered in applying the classical approaches.

Artificial Gene Regulatory Networks—A Review

The concept of gene regulation is discussed, the current state of the art in gene regulatory networks are described, including modeling and simulation, and their use in artificial evolutionary settings is reviewed.

A computational framework for qualitative simulation of nonlinear dynamical models of gene-regulatory networks

The work herein presented establishes the computational groundwork for a sound and a complete algorithm capable to capture the dynamical properties that depend only on the network structure and are invariant for ranges of values of kinetic parameters.

Hybrid Modeling and Simulation of Genetic Regulatory Networks: A Qualitative Approach

A method for the hybrid modeling and simulation of genetic regulatory networks, based on a class of piecewiselinear (PL) differential equations that has been well-studied in mathematical biology, which makes qualitative predictions of the behavior of regulatory systems.

Hybrid modeling and simulation of genetic regulatory networks

A method for the hybrid modeling and simulation of genetic regulatory networks, based on a class of piecewise-linear (PL) differential equations that has been well-studied in mathematical biology, is presented.

Gene Regulatory Networks: A Primer in Biological Processes and Statistical Modelling.

This chapter describes the different interactions controlling each step of the expression process, from transcription to mRNA and protein decay, and provides statistical tools to accurately represent this biological complexity in the form of mathematical models.

Robust dynamics in minimal hybrid models of genetic networks

  • T. PerkinsR. WildsL. Glass
  • Biology
    Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
  • 2010
It is proposed that a class of hybrid systems can be used to relate the structure of these networks to their dynamics and provide insight into the origin of robustness and the methods applied to control of the cell cycle in yeast.



Hybrid Modeling and Simulation of Biomolecular Networks

A hybrid systems approach to modeling the intra-cellular network using continuous differential equations to model the feedback mechanisms and mode-switching to describe the changes in the underlying dynamics.

The engineering of gene regulatory networks.

How networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo are discussed.

Stochastic mechanisms in gene expression.

  • H. McAdamsA. Arkin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
This work has analyzed the chemical reactions controlling transcript initiation and translation termination in a single such "genetically coupled" link as a precursor to modeling networks constructed from many such links.

Modeling the complexity of genetic networks: Understanding multigenic and pleiotropic regulation

An introduction to Boolean networks and their relevance to present-day experimental research is provided, bringing us closer to an understanding of complex molecular physiological processes like brain development and intractable medical problems of immediate importance.

Modeling transcriptional control in gene networks—methods, recent results, and future directions

The dynamic behaviors expected from model gene networks incorporating common biochemical motifs are reviewed, and current methods for modeling genetic networks areCompared, and qualitative modeling will need to be supplanted by quantitative models for specific systems.

From Boolean to probabilistic Boolean networks as models of genetic regulatory networks

The central theme in this paper is the Boolean formalism as a building block for modeling complex, large-scale, and dynamical networks of genetic interactions and its relationships to nonlinear digital filters.

Engineering stability in gene networks by autoregulation

Simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli are designed and constructed and the gain of stability produced by negative feedback is shown.

From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli.

This paper presents a global characterization of the transcriptional regulation in Escherichia coli on the basis of the current data, with special emphasis given to circular sequences of interactions ("circuits") because of their critical dynamical properties.

Simulation of prokaryotic genetic circuits.

Simulations using realistic, molecular-level models of genetic mechanisms and of signal transduction networks are needed to analyze dynamic behavior of multigene systems, to predict behavior of mutant circuits, and to identify the design principles applicable to design of genetic regulatory circuits.

On the relationship between genomic regulatory element organization and gene regulatory dynamics.

The paper ends with an analysis of a two-gene regulation system, the results of which point to the existence of a "soft-switching" mechanism that may account for the "on-off" hypothesized behavior of some gene networks.