Background: With recent increase in affordability and accessibility of high-performance computing (HPC), the use of large stochastic models has become increasingly popular for its ability to accurately mimic the behavior of the represented biochemical system. One important application of such models is to predict parameter configurations that yield an event of scientific significance. Due to the high computational requirements of Monte Carlo simulations and dimensionality of parameter space, brute force search is computationally infeasible for most large models.
Results: We have developed a novel parameter estimation algorithm-Stochastic Parameter Search for Events (SParSE)-that automatically computes parameter configurations for propagating the system to produce an event of interest at a user-specified success rate and error tolerance. Our method is highly automated and parallelizable. In addition, computational complexity does not scale linearly with the number of unknown parameters; all reaction rate parameters are updated concurrently at the end of each iteration in SParSE. We apply SParSE to three systems of increasing complexity: birth-death, reversible isomerization, and Susceptible-Infectious-Recovered-Susceptible (SIRS) disease transmission. Our results demonstrate that SParSE substantially accelerates computation of the parametric solution hyperplane compared to uniform random search. We also show that the novel heuristic for handling over-perturbing parameter sets enables SParSE to compute biasing parameters for a class of rare events that is not amenable to current algorithms that are based on importance sampling.
Conclusions: SParSE provides a novel, efficient, event-oriented parameter estimation method for computing parametric configurations that can be readily applied to any stochastic systems obeying chemical master equation (CME). Its usability and utility do not diminish with large systems as the algorithmic complexity for a given system is independent of the number of unknown reaction rate parameters.