Genetic Network Analyzer : Modelling and simulation of genetic regulatory networks

Genetic Network Analyzer (GNA) is a computer tool for the modeling and simulation of genetic regulatory networks. The aim of GNA is to assist biologists and bioinformaticians in constructing a model of a genetic regulatory network using knowledge about regulatory interactions in combination with gene expression data.

Genetic Network Analyzer consists of a simulator of qualitative models of genetic regulatory networks in the form of piecewise-linear differential equations. Instead of exact numerical values for the parameters, which are often not available for networks of biological interest, the user of GNA specifies inequality constraints. This information is sufficient to generate a state transition graph that describes the qualitative dynamics of the network. The simulator has been implemented in Java 1.5 and has been applied to the analysis of various regulatory systems, such as the networks controlling the initiation of sporulation in B. subtilis and the carbon starvation response in E. coli. See the website of Genostar for references to these and other examples.

Functionalities of GNA

The current version is GNA 7.0. In comparison with the previously distributed versions, GNA 7.0 has the following additional functionalities :

  The specification of the qualitative dynamics of a network in temporal logic, using high-level query templates ;
  The automated verification of these properties on the state transition graph by means of standard model-checking tools, either locally installed or accessible through a remote web server.

GNA 7.0 preserves all functionalities of previous versions, including :

  The construction of a model using a graphical user interface ;
  The performance of a qualitative simulation of the network dynamics, resulting in predictions adapted to available gene expression data ;
  The location of all steady states of the model, including an indication of their stability ;
  The export and import of models in SBML format.

Obtaining and using Genetic Network Analyzer

Genetic Network Analyzer is freely available for non-profit academic research by making a user licence request. Non-academic users wishing to use GNA - or academic users wishing to use GNA for purposes not covered by the user licence - are invited to contact the Genostar company. Genostar has integrated GNA in its IOGMA environment for exploratory genomics.

More information on how to use GNA can be found in the tutorial and the installation guide.

Developers of Genetic Network Analyzer

The main developers of GNA are Bruno Besson, Estelle Dumas, Hidde de Jong, Pedro Monteiro, and Michel Page.

Literature

H. de Jong, J. Geiselmann, C. Hernandez, M. Page (2003), Genetic Network Analyzer : Qualitative simulation of genetic regulatory networks, Bioinformatics, 19(3):336-344.

G. Batt, D. Ropers, H. de Jong, J. Geiselmann, R. Mateescu, M. Page, D. Schneider (2005), Validation of qualitative models of genetic regulatory networks by model checking : Analysis of the nutritional stress response in Escherichia coli, Bioinformatics, 21(Suppl 1) :i19-i28.

H. de Jong, M. Page (2008), Search for steady states of piecewise-linear differential equation models of genetic regulatory networks, ACM/IEEE Transactions on Computational Biology and Bioinformatics, 5(2):208-222.

P.T. Monteiro, D. Ropers, R. Mateescu, A.T. Freitas, H. de Jong (2008), Temporal logic patterns for querying dynamic models of cellular interaction networks, Bioinformatics, 24(16) :i227-i233.

Acknowledgments

GNA uses the following open-source software : JGraph, SAT4J, and CUP. The model-checker web server at INRIA runs NuSMV.