In order to cope with the large amounts of data that have become available in genomics, mathematical tools for the analysis of networks of interactions between genes, proteins, and other molecules are indispensable. We present a method for the qualitative simulation of genetic regulatory networks, based on a class of piecewise-linear (PL) differential equations that has been well-studied in mathematical biology. The simulation method is well-adapted to state-of-the-art measurement techniques in genomics, which often provide qualitative and coarsegrained descriptions of genetic regulatory networks. Given a qualitative model of a genetic regulatory network, consisting of a system of PL differential equations and inequality constraints on the parameter values, the method produces a graph of qualitative states and transitions between qualitative states, summarizing the qualitative dynamics of the system. The qualitative simulation method has been implemented in Java in the computer tool Genetic Network Analyzer.

GNA and the model of the sporulation network are available at http://www-helix.inrialpes.fr/gna.

BackgroundQualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.ResultsWe present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models.ConclusionsSBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

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GNA and the model of the stress response network are available at http://www-helix.inrialpes.fr/gna.

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Under conditions of nutrient deprivation, the Gram positive soil bacterium Bacillus subtilis can abandon vegetative growth and form a dormant, environmentally-resistant spore instead. The decision to either divide or sporulate is controlled by a large and complex genetic regulatory network integrating various environmental, cell-cycle, and metabolic signals. Although sporulation in B. subtilis is one of the best-understood model systems for prokaryotic development, very little quantitative data on kinetic parameters and molecular concentrations are available. A qualitative simulation method is used to model the sporulation network and simulate the response of the cell to nutrient deprivation. Using this method, we have been able to reproduce essential features of the choice between vegetative growth and sporulation, in particular the role played by competing positive and negative feedback loops.