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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.

Background: Given its recent rapid development and the central role that modeling plays in the discipline, systems biology clearly needs methods for automated modeling of dynamical systems. Process-based modeling focuses on explanatory models of dynamical systems; it constructs such models from measured time-course data and formalized modeling knowledge. In this paper, we apply process-based modeling to the practically relevant task of modeling the Rab5-Rab7 conversion switch in endocytosis. The task is difficult due to the limited observability of the system variables and the noisy measurements, which pose serious challenges to the process of model selection. To address these issues, we propose a domain-specific model selection criteria that take into account knowledge about the necessary properties of the simulated model behavior., Results: In a series of modeling experiments, we compare the results of process-based modeling obtained with different model selection criteria. The first is the standard maximum likelihood criterion based solely on least-squares model error. The second one is a parsimony-based criterion that also takes into account model complexity. We also introduce three domain-specific criteria based on domain expert expectations about the simulated behavior of an endocytosis model. According to the first criterion, 90 of the candidate models are indistinguishable. Furthermore, taking into account the complexity of the model does not lead to better model selection. However, the use of domain-specific criteria results in a remarkable improvement over the other two model selection criteria., Conclusions: We demonstrate the applicability of process-based modeling to the task of modeling the Rab5-Rab7 dynamics in endocytosis. Our experiments show that the domain-specific criteria outperform the standard domain-independent criteria for model selection. We also find that some of the model structures discarded as implausible in previous studies lead to the expected Rab5-Rab7 switch behavior.