title: Modelling and analysis of the sugar cataract development process using stochastic hybrid systems.
abstract: Modelling and analysis of biochemical systems such as sugar cataract development (SCD) are critical because they can provide new insights into systems, which cannot be easily tested with experiments; however, they are challenging problems due to the highly coupled chemical reactions that are involved. The authors present a stochastic hybrid system (SHS) framework for modelling biochemical systems and demonstrate the approach for the SCD process. A novel feature of the framework is that it allows modelling the effect of drug treatment on the system dynamics. The authors validate the three sugar cataract models by comparing trajectories computed by two simulation algorithms. Further, the authors present a probabilistic verification method for computing the probability of sugar cataract formation for different chemical concentrations using safety and reachability analysis methods for SHSs. The verification method employs dynamic programming based on a discretisation of the state space and therefore suffers from the curse of dimensionality. To analyse the SCD process, a parallel dynamic programming implementation that can handle large, realistic systems was developed. Although scalability is a limiting factor, this work demonstrates that the proposed method is feasible for realistic biochemical systems.
authors.affiliation: Vanderbilt University, ISIS/EECS, Nashville, USA. derek.riley@vanderbilt.edu
authors.forename: D
authors.initials: D
authors.lastname: Riley
authors.forename: X
authors.initials: X
authors.lastname: Koutsoukos
authors.forename: K
authors.initials: K
authors.lastname: Riley
mesh_terms: D000465:Algorithms; D001669:Biochemical Phenomena; D002386:Cataract / Q000209:etiology / Q000378:metabolism*; D003198:Computer Simulation; D008954:Models, Biological; D008956:Models, Chemical; D013012:Sorbitol / Q000378:metabolism*; D013269:Stochastic Processes; D049490:Systems Biology / Q000379:methods
chemical_list: D013012:Sorbitol