Abstract

BackgroundIdentifying 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.ResultsWe 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.ConclusionsThe 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.

Highlights

  • Identifying a proper model structure, using methods that address both structural and parameter uncertainty, is a crucial problem within the systems approach to biology

  • Considering a dynamical biological system to be a well-stirred mixture of its constituents, the most commonly used mathematical model of its dynamics takes the form of a system of coupled ordinary differential equations, treating the entity properties as continuous and assuming they evolve deterministically through time

  • Process-based modeling Scientists often describe dynamical systems in terms of processes that govern the system dynamics and the entities involved in the processes1

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Summary

Introduction

Identifying a proper model structure, using methods that address both structural and parameter uncertainty, is a crucial problem within the systems approach to biology. It has a marginal presence in the recent literature. Stochastic fluctuations are responsible for the divergence in phenotype and genetic activities [3,4,5] In such cases, models based on stochastic kinetics are more suitable, as they allow for treating of the modeled systems as either discrete or continuous in terms of the properties of the observed entities and stochastic in terms of the reactions between them

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