Shuttleworth, Joseph G. and Lei, Chon Lok and Windley, Monique J. and Hill, Adam P. and Preston, Simon P. and Mirams, Gary R. (2025) Evaluating the predictive accuracy of ion-channel models using data from multiple experimental designs. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 383 (2292). ISSN 1364-503X
Full text not available from this repository.Abstract
Mathematical models are increasingly being relied upon to provide quantitatively accurate predictions of cardiac electrophysiology. Many such models concern the behaviour of particular subcellular components (namely, ion channels) which, together, allow the propagation of electrical signals through heart-muscle tissue; that is, the firing of action potentials. In particular, I Kr , a voltage-sensitive potassium ion-channel current, is of interest owing to the central pore of its primary protein having a propensity to blockage by various small molecules. We use newly collected data obtained from an ensemble of voltage-clamp experiment designs (protocols) to validate the predictive accuracy of various dynamical models of I Kr . To do this, we fit models to each protocol individually and quantify the error in the resultant model predictions for other protocols. This allows the comparison of predictive accuracy for I Kr models under a diverse collection of previously unexplored dynamics. Our results highlight heterogeneity between parameter estimates obtained from different cells, suggesting the presence of latent effects not yet accounted for in our models. This heterogeneity has a significant effect on our parameter estimates and suggests routes for model improvement.
This article is part of the theme issue ‘Uncertainty quantification for healthcare and biological systems (Part 1)’.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:53 |
| Last Modified: | 05 May 2025 06:53 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1698 |
Actions (login required)
 |
View Item |