Accelerated Biochemical Kinetic Model Fitting via the Asynchronous, Generalized Island Method

Abstract

Mechanistic kinetic models of biological pathways are an important tool for understanding biological systems. Constructing kinetic models requires fitting the parameters to experimental data. However, parameter fitting on these models is a non–convex, non–linear optimization problem. Many algorithms have been proposed to addressing optimization for parameter fitting including globally convergent, population–based algorithms. The computational complexity of the this optimization for even modest models means that parallelization is essential. Past approaches to parameter optimization have focused on parallelizing a particular algorithm. However, this requires re–implementing the algorithm usinga distributed computing framework, which requires a significant investment of time and effort. There are two major drawbacks of this approach: First, the choice of best algorithm may depend on the model. Given the large variety of optimization algorithms available, it is difficult to re–implement every potentially useful algorithm. Second, when new advances are made in a given optimization algorithm, the parallel implementation must be updated to take advantage of these advantages. Thus, there is a continual burden placed on the parallel implementation. The drawbacks of re–implementing algorithms lead us to a different approach to parallelizing parameter optimization. Instead of parallelizing the algorithms themselves, we run many instances of the algorithm on single cores. This provides great flexibility as to the choice of algorithms by allowing us to reuse previous implementations. Also, it does not require the creation and maintenance of parallel versions of optimization algorithms. This approach is known as the island method. To our knowledge, the utility of the island method for parameter fitting in systems biology has not been previously demonstrated. For the parameter fitting problem, we allow islands to exchange information about their “best” solutions so that all islands leverage the discoveries of the few. This turns out to be avery effective in practice, leading to super–linear speedups. That is, if a single processor finds the optimal value of parameters in time t, then N processors exchanging information in this way find the optimal value much faster than t/N. We show that the island method is able to consistently provide good speedups for these problems. We also benchmark the island method against a variety of large, challenging kinetic models and show that it is able to consistently improve the quality of fit in less time than a single–threaded implementation.Our software is available at https://github.com/sys-bio/sabaody under a Apache 2.0 license.Contactmailto:medjk@comcast.net