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Bayesian Sensitivity Analysis of a Cardiac Cell Model Using a Gaussian Process Emulator.

Chang ET, Strong M, Clayton RH - PLoS ONE (2015)

Bottom Line: In this study we show that a surrogate statistical model of a cardiac cell model (the Luo-Rudy 1991 model) can be built using Gaussian process (GP) emulators.We found that the GP emulators could be fitted to a small number of model runs, and behaved as would be expected based on the underlying physiology that the model represents.We have shown that an emulator approach is a powerful tool for uncertainty and sensitivity analysis in cardiac cell models.

View Article: PubMed Central - PubMed

Affiliation: Insigneo Institute for in-silico Medicine, University of Sheffield, Sheffield, United Kingdom; Department of Computer Science University of Sheffield, Sheffield, United Kingdom.

ABSTRACT
Models of electrical activity in cardiac cells have become important research tools as they can provide a quantitative description of detailed and integrative physiology. However, cardiac cell models have many parameters, and how uncertainties in these parameters affect the model output is difficult to assess without undertaking large numbers of model runs. In this study we show that a surrogate statistical model of a cardiac cell model (the Luo-Rudy 1991 model) can be built using Gaussian process (GP) emulators. Using this approach we examined how eight outputs describing the action potential shape and action potential duration restitution depend on six inputs, which we selected to be the maximum conductances in the Luo-Rudy 1991 model. We found that the GP emulators could be fitted to a small number of model runs, and behaved as would be expected based on the underlying physiology that the model represents. We have shown that an emulator approach is a powerful tool for uncertainty and sensitivity analysis in cardiac cell models.

No MeSH data available.


Design data and test data obtained from 220 runs of the LR1991 model for eight outputs and six inputs.Each plot shows combinations of inputs and outputs, with 200 coloured points indicating design data used to fit the emulators, and 20 grey points showing test data used to validate the emulator.
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pone.0130252.g002: Design data and test data obtained from 220 runs of the LR1991 model for eight outputs and six inputs.Each plot shows combinations of inputs and outputs, with 200 coloured points indicating design data used to fit the emulators, and 20 grey points showing test data used to validate the emulator.

Mentions: The design data inputs and outputs are plotted in Fig 2, where each plot shows one of the eight output quantities plotted against one of the six input quantities. Test data are overlaid as dark grey points. Several associations are immediately clear from this figure, for example maximum dVm/dT and peak Vm are both strongly associated with GNa and weakly associated, if at all, with the other inputs. On the other hand, APD90 shows shows some dependence on Gsi, GK, and Gb. Note that the inputs have been normalised such that they to lie in the (0,1) interval. The uniform sampling distribution for the inputs is clear from the even spread of points in the (0,1) interval.


Bayesian Sensitivity Analysis of a Cardiac Cell Model Using a Gaussian Process Emulator.

Chang ET, Strong M, Clayton RH - PLoS ONE (2015)

Design data and test data obtained from 220 runs of the LR1991 model for eight outputs and six inputs.Each plot shows combinations of inputs and outputs, with 200 coloured points indicating design data used to fit the emulators, and 20 grey points showing test data used to validate the emulator.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482712&req=5

pone.0130252.g002: Design data and test data obtained from 220 runs of the LR1991 model for eight outputs and six inputs.Each plot shows combinations of inputs and outputs, with 200 coloured points indicating design data used to fit the emulators, and 20 grey points showing test data used to validate the emulator.
Mentions: The design data inputs and outputs are plotted in Fig 2, where each plot shows one of the eight output quantities plotted against one of the six input quantities. Test data are overlaid as dark grey points. Several associations are immediately clear from this figure, for example maximum dVm/dT and peak Vm are both strongly associated with GNa and weakly associated, if at all, with the other inputs. On the other hand, APD90 shows shows some dependence on Gsi, GK, and Gb. Note that the inputs have been normalised such that they to lie in the (0,1) interval. The uniform sampling distribution for the inputs is clear from the even spread of points in the (0,1) interval.

Bottom Line: In this study we show that a surrogate statistical model of a cardiac cell model (the Luo-Rudy 1991 model) can be built using Gaussian process (GP) emulators.We found that the GP emulators could be fitted to a small number of model runs, and behaved as would be expected based on the underlying physiology that the model represents.We have shown that an emulator approach is a powerful tool for uncertainty and sensitivity analysis in cardiac cell models.

View Article: PubMed Central - PubMed

Affiliation: Insigneo Institute for in-silico Medicine, University of Sheffield, Sheffield, United Kingdom; Department of Computer Science University of Sheffield, Sheffield, United Kingdom.

ABSTRACT
Models of electrical activity in cardiac cells have become important research tools as they can provide a quantitative description of detailed and integrative physiology. However, cardiac cell models have many parameters, and how uncertainties in these parameters affect the model output is difficult to assess without undertaking large numbers of model runs. In this study we show that a surrogate statistical model of a cardiac cell model (the Luo-Rudy 1991 model) can be built using Gaussian process (GP) emulators. Using this approach we examined how eight outputs describing the action potential shape and action potential duration restitution depend on six inputs, which we selected to be the maximum conductances in the Luo-Rudy 1991 model. We found that the GP emulators could be fitted to a small number of model runs, and behaved as would be expected based on the underlying physiology that the model represents. We have shown that an emulator approach is a powerful tool for uncertainty and sensitivity analysis in cardiac cell models.

No MeSH data available.