Title
Parameter sensitivity analysis of a human atrial cell model using multivariate regression
Abstract
Atrial cell models form the building blocks of complex multicellular models and contain many input parameters within a large parameter space. A rapid systematic way of quantifying changes in model outputs due to input parameter variability would enhance mechanistic understanding. A parameter sensitivity study on input model conductances within the Courtemanche-Ramirez-Nattel (CRN) human atrial cell model was performed. Input maximal ionic conductances were varied by randomly scaling baseline model values, and used in single cell action potential (AP) simulations. Multivariable regression was performed to find regression matrix B which minimised differences between output Y and predicted Y * = XB. Regression values were mean-centred and normalized to SD, such that a +0.5 value implied parameter input 1SD above mean increased output by 0.5SD. AP determinants were compared (n = 100). dV=dtmax and Vamp showed strong sensitivity only to maximal sodium conductance GNa, whilst APD and tpeak were weakly sensitive to multiple conductances. Predicted outputs showed strong correlation to measured values: 0.880 ≤ R2 ≤ 0.998 for measured AP determinants. Multivariable regression is a novel tool for examining parameter sensitivity of the CRN AP model and offers rapid insight to the relative importance of input parameters to specific outputs.
Year
Venue
Keywords
2014
CinC
bioelectric potentials,biomechanics,cardiology,cellular biophysics,physiological models,regression analysis,ap determinants,crn ap model,courtemanche-ramirez-nattel human atrial cell model,complex multicellular models,human atrial cell model,maximal ionic conductances,multivariable regression,multivariate regression,parameter sensitivity analysis,single cell action potential,mathematical model,computational modeling,predictive models,data models,sensitivity
Field
DocType
Volume
Multivariable calculus,Normalization (statistics),Biological system,Regression,Multivariate statistics,Correlation,Parameter space,Conductance,Statistics,Scaling,Mathematics
Conference
41
ISSN
Citations 
PageRank 
2325-8861
0
0.34
References 
Authors
0
2
Name
Order
Citations
PageRank
Chang, E.T.Y.141.79
Clayton, R.H.200.34