fda / cipa Goto Github PK

View Code? Open in Web Editor NEW

32.0 12.0 19.0 148.41 MB

License: GNU General Public License v3.0

R 67.18% C 25.16% Shell 7.66%

cipa's Introduction

Comprehensive in vitro Proarrhythmia Assay (CiPA)
in silico model

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

Authors

Kelly Chang, Zhihua Li

Requirements

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)

Uncertainty characterization

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).

Uncertainty propagation

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).

DISCLAIMER

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.

cipa's People

Contributors

Stargazers

Watchers

Forkers

bridder kimmingul konkuk-univ pipetcpt mutaz94 pyncx mishalashraf imansamiee xiaomei-han huang961372045 frodofine jmm-123 zhouzhoutong rnaimehaom cyto-lars chamaeleon

cipa's Issues

Difference in model equations

It seems that the github hergmod.c file contains different equations, than those published in Li et al 2018 (https://doi.org/10.1161/CIRCEP.116.004628), please see attached slides for details. Could the authors please clarify the exact equations that should be used in model fitting.

Many Thanks

github code vs Li et al 2018.pptx

No newordherg_qNet.so files in hERG_fitting/models folder

Error in sprintf("%s not found! Interpreting dose as nanomolar concentrations.") issue

I have the problem associated with sprint error in R 3.6.3(using Rstudio terminal tab).
Let me know how to solve below error.

-Command used in Rstudio terminal tab-

   Rscript AP_simulation.R -d drug1 -x "1-10,15,20,25" --cmaxfile="my_cmax_table.csv" --hergpath="path/to/herg/results/" --hillpath="path/to/hill/results/"-

-Error result example-

   loaded via a namespace (and not attached):
   [1] compiler_3.6.3 getopt_1.20.3
   Error in sprintf("%s not found! Interpreting dose as nanomolar concentrations.") :

   Calls: print -> sprintf

-Rcode part(AP_simulation.R) that may occur error-

  #--- get therapeutic concentration (Cmax)
      if(drug=="control"){
        cmax<-0
      }else{
      if(!file.exists(cmaxfile)){
        cmax<-1
       print(sprintf("%s not found! Interpreting dose as nanomolar concentrations."))
      }else{
      drugtable<-read.csv(cmaxfile)
      cmax<-drugtable[as.character(drugtable$drug)==drug,"therapeutic"] # should be in nanomolar
      if(length(cmax)==0){
       cmax<-1
       print(sprintf("Cmax undefined, interpreting dose as nanomolar concentrations."))
      }else if(length(cmax)==1){
       print(sprintf("Cmax set to %g nM, interpreting dose as multiples of Cmax.",cmax))
      }else{
        stop("Multiple entries for %s therapeutic concentration!",drug)
      }
    }
   }

dyn.load error issue.

extension<-ifelse(isWindows, ".dll", ".so")
dyn.load(paste0("D:/platanus/CiPA_Rocde/CiPA-master/AP_simulation/models/newordherg_qNet",extension))

Error in inDL(x, as.logical(local), as.logical(now), ...) :
unable to load shared object 'D:/platanus/CiPA_Rocde/CiPA-master/AP_simulation/models/newordherg_qNet.dll'
LoadLibrary failure: The specified module could not be found.

May be..... Does it occur error because of Rtool version?

I'm using R 3.6.3 version and Rtool35 version based on window10.

Run Rscript compute_TdP_error.R issue

I'm running the compute_TdP_error.R script and the following error occurs.

This error message appears 25 times, I guess it happens in a ‘for’
I debugged the code and found that the problem occurred in # for outdir

What is the cause of this?

Issue loading newordherg_qNet model

Could you please help resolve the issue or post .dll file?
Thank you!