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A Model Checking Approach to the Parameter Estimation of Biochemical Pathways

  • Robin Donaldson
  • David Gilbert
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5307)

Abstract

Model checking has historically been an important tool to verify models of a wide variety of systems. Typically a model has to exhibit certain properties to be classed ‘acceptable’. In this work we use model checking in a new setting; parameter estimation. We characterise the desired behaviour of a model in a temporal logic property and alter the model to make it conform to the property (determined through model checking). We have implemented a computational system called MC2(GA) which pairs a model checker with a genetic algorithm. To drive parameter estimation, the fitness of set of parameters in a model is the inverse of the distance between its actual behaviour and the desired behaviour. The model checker used is the simulation-based Monte Carlo Model Checker for Probabilistic Linear-time Temporal Logic with numerical constraints, MC2(PLTLc). Numerical constraints as well as the overall probability of the behaviour expressed in temporal logic are used to minimise the behavioural distance. We define the theory underlying our parameter estimation approach in both the stochastic and continuous worlds. We apply our approach to biochemical systems and present an illustrative example where we estimate the kinetic rate constants in a continuous model of a signalling pathway.

Keywords

Nerve Growth Factor Model Check Temporal Logic Free Variable Kinetic Rate Constant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Robin Donaldson
    • 1
  • David Gilbert
    • 1
  1. 1.Bioinformatics Research CentreUniversity of GlasgowGlasgowScotland, UK

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