R code used to perform uncertainty quantification for the CiPA in silico model

Kelly Chang, Zhihua Li

This code was developed with R version 3.3 and uses the following packages:

• optparse (version 1.4.4)
• deSolve (version 1.14)
• cmaes (version 1.0-11)
• FME (version 1.3.5)
• rms (4.5-0)
• ggplot2 (version 1.14)

hERG_fitting/ contains code to perform uncertainty characterization for drug binding kinetics of the human Ether-à-go-go-Related Gene (hERG) channel gating model (README.md).

Hill_fitting/ contains code to perform uncertainty characterization of dose-response curves for six ionic currents (ICaL, INaL, INa, Ito, IKs, and IK1) (README.md).

AP_simulation/ contains code to propagate uncertainty in drug effects to action potential (AP) simulations. Results from hERG_fitting/ and Hill_fitting/ are used as model inputs (README.md).

This software and documentation were developed by the authors in their capacities as Oak Ridge Institute for Science and Education (ORISE) research fellows at the U.S. Food and Drug Administration (FDA).

FDA assumes no responsibility whatsoever for use by other parties of the Software, its source code, documentation or compiled executables, and makes no guarantees, expressed or implied, about its quality, reliability, or any other characteristic. Further, FDA makes no representations that the use of the Software will not infringe any patent or proprietary rights of third parties. The use of this code in no way implies endorsement by the FDA or confers any advantage in regulatory decisions.