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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.


Sensitivity indices in APD90 emulator.Sensitivity index of each of the inputs on APD90, showing the proportion of total variance that can be attributed to variance in each input.
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pone.0130252.g006: Sensitivity indices in APD90 emulator.Sensitivity index of each of the inputs on APD90, showing the proportion of total variance that can be attributed to variance in each input.

Mentions: Figs 5 and 6 show the result of sensitivity analysis using the APD90 emulator. Fig 5 shows the mean effects, which are the conditional expectation of the output, as each input in turn was fixed and varied from 0 to 1, while all other inputs were assigned a mean of 0.5 and a variance of 0.04. Increasing GK, Gb, and GK1 above their mean value of 0.5 acted to decrease mean APD90 in the emulator, whereas increasing Gsi above 0.5 acted to increase mean APD90. These observations are consistent with the operation of the LR1991 model, where GK, Gb, and GK1 control outward depolarising currents, and Gsi controls an inward depolarising current. The trends shown in Fig 5 can also be seen in the scatter plots of the design data in Fig 2.


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

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

Sensitivity indices in APD90 emulator.Sensitivity index of each of the inputs on APD90, showing the proportion of total variance that can be attributed to variance in each input.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130252.g006: Sensitivity indices in APD90 emulator.Sensitivity index of each of the inputs on APD90, showing the proportion of total variance that can be attributed to variance in each input.
Mentions: Figs 5 and 6 show the result of sensitivity analysis using the APD90 emulator. Fig 5 shows the mean effects, which are the conditional expectation of the output, as each input in turn was fixed and varied from 0 to 1, while all other inputs were assigned a mean of 0.5 and a variance of 0.04. Increasing GK, Gb, and GK1 above their mean value of 0.5 acted to decrease mean APD90 in the emulator, whereas increasing Gsi above 0.5 acted to increase mean APD90. These observations are consistent with the operation of the LR1991 model, where GK, Gb, and GK1 control outward depolarising currents, and Gsi controls an inward depolarising current. The trends shown in Fig 5 can also be seen in the scatter plots of the design data in Fig 2.

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.