Reducing complexity and unidentifiability when modelling human atrial cells
File(s)
Published version
Author(s)
Houston, C
Marchand, B
Engelbert, L
Cantwell, CD
Type
Journal Article
Abstract
Mathematical models of a cellular action potential in cardiac modelling have become increasingly complex, particularly in gating kinetics which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalised medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the action potential. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed.
Date Issued
2020-05-25
Date Acceptance
2020-02-20
Citation
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 2020, 378 (2173), pp.1-17
ISSN
1364-503X
Publisher
Royal Society, The
Start Page
1
End Page
17
Journal / Book Title
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
Volume
378
Issue
2173
Copyright Statement
© 2020 The Authors.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Sponsor
British Heart Foundation
Identifier
http://arxiv.org/abs/2001.10954v1
Grant Number
PG/15/59/31621
Subjects
q-bio.QM
q-bio.QM
stat.AP
stat.CO
stat.ML
Notes
15 pages, 6 figures, submitted to Philosophical Transactions A
Publication Status
Published
Date Publish Online
2020-05-25