Open Access Green as soon as Postprint is submitted to ZB.
Parameter estimation for dynamical systems with discrete events and logical operations.
Bioinformatics 33, 1049-1056 (2017)
Publ. Version/Full Text Research data DOI
Motivation: Ordinary differential equation (ODE) models are frequently used to describe the dynamic behaviour of biochemical processes. Such ODE models are often extended by events to describe the effect of fast latent processes on the process dynamics. To exploit the predictive power of ODE models, their parameters have to be inferred from experimental data. For models without events, gradient based optimization schemes perform well for parameter estimation, when sensitivity equations are used for gradient computation. Yet, sensitivity equations for models with parameter- and state-dependent events and event-triggered observations are not supported by existing toolboxes. Results: In this manuscript, we describe the sensitivity equations for differential equation models with events and demonstrate how to estimate parameters from event-resolved data using event-triggered observations in parameter estimation. We consider a model for GFP expression after transfection and a model for spiking neurons and demonstrate that we can improve computational efficiency and robustness of parameter estimation by using sensitivity equations for systems with events. Moreover, we demonstrate that, by using event-outputs, it is possible to consider event-resolved data, such as time-to-event data, for parameter estimation with ODE models. By providing a user-friendly, modular implementation in the toolbox AMICI, the developed methods are made publicly available and can be integrated in other systems biology toolboxes. Availability and Implementation: We implement the methods in the open-source toolbox Advanced MATLAB Interface for CVODES and IDAS (AMICI, https://github.com/ICB-DCM/AMICI).
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Profile Likelihood; Cellular-systems; Spike Trains; Biology; Models; Simulation; Networks; Sbml; Identifiability; Optimization
ISSN (print) / ISBN 1367-4803
Quellenangaben Volume: 33, Issue: 7, Pages: 1049-1056
Publisher Oxford University Press
Publishing Place Oxford
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)