Background: Identifying a proper model structure, using methods that address both structural and parameter uncertainty, is a crucial problem within the systems approach to biology. And yet, it has a marginal presence in the recent literature. While many existing approaches integrate methods for simulation and parameter estimation of a single model to address parameter uncertainty, only few of them address structural uncertainty at the same time. The methods for handling structure uncertainty often oversimplify the problem by allowing the human modeler to explicitly enumerate a relatively small number of alternative model structures. On the other hand, process-based modeling methods provide flexible modular formalisms for specifying large classes of plausible model structures, but their scope is limited to deterministic models. Here, we aim at extending the scope of process-based modeling methods to inductively learn stochastic models from knowledge and data.
Results: We combine the flexibility of process-based modeling in terms of addressing structural uncertainty with the benefits of stochastic modeling. The proposed method combines search trough the space of plausible model structures, the parsimony principle and parameter estimation to identify a model with optimal structure and parameters. We illustrate the utility of the proposed method on four stochastic modeling tasks in two domains: gene regulatory networks and epidemiology. Within the first domain, using synthetically generated data, the method successfully recovers the structure and parameters of known regulatory networks from simulations. In the epidemiology domain, the method successfully reconstructs previously established models of epidemic outbreaks from real, sparse and noisy measurement data.
Conclusions: The method represents a unified approach to modeling dynamical systems that allows for flexible formalization of the space of candidate model structures, deterministic and stochastic interpretation of model dynamics, and automated induction of model structure and parameters from data. The method is able to reconstruct models of dynamical systems from synthetic and real data.
Keywords: Compartmental epidemiological models; Dynamical systems; Genetic regulatory networks; Process-based modeling; Stochastic models; Structural uncertainty.