In this paper, a discrete event based mechanistic simulation platform DEMSIM is developed for testing and validating putative regulatory interactions. The proposed framework models the main processes in gene expression, which are transcription, translation and decay processes, as stand-alone modules while superimposing the regulatory circuitry to obtain an accurate time evolution of the system. The stochasticity inherent to gene expression and regulation processes is captured using Monte Carlo based sampling. The proposed framework is applied to the extensively studied lac operon system, the SOS response system and the araBAD operon system of Escherichia coli. The results for the lac gene system demonstrate the simulation framework's ability to capture the dynamics of gene regulation, whereas the results for the SOS response system indicate that the framework is able to make accurate predictions about system behavior in response to perturbations. Finally, simulation studies for the araBAD system suggest that the developed framework is able to distinguish between different plausible regulatory mechanisms postulated to explain observed gene expression profiles. Overall, the obtained results highlight the effectiveness of DEMSIM at describing the underlying biological processes involved in gene regulation for querying alternative regulatory hypotheses.
All Science Journal Classification (ASJC) codes
- Statistics and Probability
- Modeling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Agricultural and Biological Sciences(all)
- Applied Mathematics