Reducing complexity and unidentifiability when modelling human atrial cells

DOI10.1098/RSTA.2019.0339MaRDI QIDQ5154204zbMATH OpenOpenAlexWikidataFDO

Authors

Publication date 4 October 2021

Published in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences (Search for Journal in Brave)

Copyright license Creative Commons Attribution 4.0 International

Full work available at URL https://arxiv.org/abs/2001.10954

zbMATH Keywords

action potentialapproximate Bayesian computationcardiac modellingcomputational biologyuncertaintyunidentifiability

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Cell biology (92C37)

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.

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Cites work

• Detecting undetectables: can conductances of action potential models be changed without appreciable change in the transmembrane potential?
• Mathematical physiology. I: Cellular physiology
• Reducing complexity and unidentifiability when modelling human atrial cells

Cited in

(6)

• Testing the limits of cardiac electrophysiology models through systematic variation of current
• Markov chain models for cardiac rhythm dynamics in patients undergoing catheter ablation of atrial fibrillation
• A method for reduction of human ventricular action potential model
• Reducing complexity and unidentifiability when modelling human atrial cells
• Personalization of electro-mechanical models of the pressure-overloaded left ventricle: fitting of windkessel-type afterload models
• Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments

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