A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

Pedro T Monteiro,Michel Page,Ana T Freitas,Estelle Dumas,Radu Mateescu,Hidde De Jong,Bruno Besson

doi:10.1186/1471-2105-10-450

Abstract

BackgroundThe study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level.ResultsWe have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool GNA and the model checkers NUSMV and CADP. GNA has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results.ConclusionsThe practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in E. coli. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks.

Highlights

The study of biological networks has led to the development of increasingly large and detailed models
We focus on the model checking approach
In order to address these issues, we propose a service-oriented architecture (SOA) [22] for the integrated modeling and formal verification of genetic regulatory networks, which reuses existing technology as much as possible

Summary

Introduction

The study of biological networks has led to the development of increasingly large and detailed models. As the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. As the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in dozens of simulation traces This calls for the use of automated and scalable methods that help the modeler with the identification and verification of interesting dynamical properties of the network. The field of formal verification provides promising methods to prove or disprove specified properties of a system These methods proceed by an exploration of all possible behaviors of the system, following two main approaches: logic inference, based on the use of axioms and proof rules [8], and model checking, based on an automatic and exhaustive search of the state space [9]. Several examples of the application of model checking to the analysis of biological regulatory networks have been published in the literature (e.g., [10,11,12,13,14,15,16,17,18,19,20,21])

Results

Discussion

Conclusion