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Model-driven optimal experimental design for calibrating cardiac electrophysiology models
Lei,Chon Lok1,2; Clerx,Michael3; Gavaghan,David J.4,5; Mirams,Gary R.3
2023-07-06
Source PublicationComputer Methods and Programs in Biomedicine
ISSN0169-2607
Volume240Pages:107690
Abstract

Background and Objective: Models of the cardiomyocyte action potential have contributed immensely to the understanding of heart function, pathophysiology, and the origin of heart rhythm disturbances. However, action potential models are highly nonlinear, making them difficult to parameterise and limiting to describing ‘average cell’ dynamics, when cell-specific models would be ideal to uncover inter-cell variability but are too experimentally challenging to be achieved. Here, we focus on automatically designing experimental protocols that allow us to better identify cell-specific maximum conductance values for each major current type. Methods and Results: We developed an approach that applies optimal experimental designs to patch-clamp experiments, including both voltage-clamp and current-clamp experiments. We assessed the models calibrated to these new optimal designs by comparing them to the models calibrated to some of the commonly used designs in the literature. We showed that optimal designs are not only overall shorter in duration but also able to perform better than many of the existing experiment designs in terms of identifying model parameters and hence model predictive power. Conclusions: For cardiac cellular electrophysiology, this approach will allow researchers to define their hypothesis of the dynamics of the system and automatically design experimental protocols that will result in theoretically optimal designs.

KeywordAction Potential Electrophysiology Mathematical Modelling Model Calibration Optimal Experimental Design Patch Clamp
DOI10.1016/j.cmpb.2023.107690
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaComputer Science ; Engineering ; Medical Informatics
WOS SubjectComputer Science, Interdisciplinary Applications ; Computer Science, Theory & Methods ; Engineering, Biomedical ; Medical Informatics
WOS IDWOS:001046095600001
PublisherELSEVIER IRELAND LTD, ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE 00000, IRELAND
Scopus ID2-s2.0-85165226163
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Document TypeJournal article
CollectionInstitute of Translational Medicine
DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorMirams,Gary R.
Affiliation1.Institute of Translational Medicine,Faculty of Health Sciences,University of Macau,Macau,China
2.Department of Biomedical Sciences,Faculty of Health Sciences,University of Macau,Macau,China
3.Centre for Mathematical Medicine & Biology,School of Mathematical Sciences,University of Nottingham,Nottingham,United Kingdom
4.Department of Computer Science,University of Oxford,Oxford,United Kingdom
5.Doctoral Training Centre,University of Oxford,Oxford,United Kingdom
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Lei,Chon Lok,Clerx,Michael,Gavaghan,David J.,et al. Model-driven optimal experimental design for calibrating cardiac electrophysiology models[J]. Computer Methods and Programs in Biomedicine, 2023, 240, 107690.
APA Lei,Chon Lok., Clerx,Michael., Gavaghan,David J.., & Mirams,Gary R. (2023). Model-driven optimal experimental design for calibrating cardiac electrophysiology models. Computer Methods and Programs in Biomedicine, 240, 107690.
MLA Lei,Chon Lok,et al."Model-driven optimal experimental design for calibrating cardiac electrophysiology models".Computer Methods and Programs in Biomedicine 240(2023):107690.
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