Journal of Computational Physics
Bio-PEPA: An Extension of the Process Algebra PEPA for Biochemical Networks
Electronic Notes in Theoretical Computer Science (ENTCS)
Bio-PEPA: A framework for the modelling and analysis of biological systems
Theoretical Computer Science
Transactions on Computational Systems Biology XI
Sensitivity analysis of stochastic models of bistable biochemical reactions
SFM'08 Proceedings of the Formal methods for the design of computer, communication, and software systems 8th international conference on Formal methods for computational systems biology
Equivalence and Discretisation in Bio-PEPA
CMSB '09 Proceedings of the 7th International Conference on Computational Methods in Systems Biology
A semantic equivalence for Bio-PEPA based on discretisation of continuous values
Theoretical Computer Science
Modelling non-linear crowd dynamics in bio-PEPA
FASE'11/ETAPS'11 Proceedings of the 14th international conference on Fundamental approaches to software engineering: part of the joint European conferences on theory and practice of software
Design and development of software tools for Bio-PEPA
Winter Simulation Conference
Equivalences for a biological process algebra
Theoretical Computer Science
Stochastic Modelling of the Kai-based Circadian Clock
Electronic Notes in Theoretical Computer Science (ENTCS)
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Circadian clocks are biochemical networks, present in nearly all living organisms, whose function is to regulate the expression of specific mRNAs and proteins to synchronise rhythms of metabolism, physiology and behaviour to the 24 hour day/night cycle. Because of their experimental tractability and biological significance, circadian clocks have been the subject of a number of computational modelling studies. In this study we focus on the simple circadian clock of the fungus Neurospora crassa . We use the Bio-PEPA process algebra to develop both a stochastic and a deterministic model of the system. The light on/off mechanism responsible for entrainment to the day/night cycle is expressed using discrete time-dependent events in Bio-PEPA. In order to validate our model, we compare it against the results of previous work which demonstrated that the deterministic model is in agreement with experimental data. Here we investigate the effect of stochasticity on the robustness of the clock's function in biological timing. In particular, we focus on the variations in the phase and amplitude of oscillations in circadian proteins with respect to different factors such as the presence/absence of a positive feedback loop, and the presence/absence of light. The time-dependent sensitivity of the model with respect to some key kinetic parameters is also investigated.