////////////////////////////////////////////////////////////////////////////////////////////////
This is a Chaste (www.cs.ox.ac.uk/chaste) Bolt-on Project that can be used to 
recreate the results of the paper

KA Beattie, C Luscombe, G Williams, J Munoz-Muriedas, DJ Gavaghan, Y Cui, GR Mirams
"Evaluation of an In Silico Cardiac Safety Assay: Using Ion Channel Screening Data to Predict 
QT Interval Changes in the Rabbit Ventricular Wedge."
Journal of Pharmacological and Toxicological Methods, 2013
http://dx.doi.org/10.1016/j.vascn.2013.04.004

It works with revision 18049 of Chaste - not a particular release version.
Please see
https://chaste.cs.ox.ac.uk/trac/wiki/ChasteGuides/ExternalDeveloperGuide
for details of checking out a particular revision.
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pIC50_Values.dat Contains all IC50 values for all the compounds from the three different assays 
       used in the evaluation where just the IC50 value was fitted from the available 
       dose-response data (and the Hill Coefficient was assumed to be 1).

pIC50_Values_And_Hill_Coefficients.dat Contains all IC50 values and Hill Coefficient for all 
       the compounds from the three different assays used in the evaluation where both the 
       IC50 value and Hill Coefficient have been fitted from the available dose-response data.
 
Rabbit_Wedge_Data.dat Contains all the data recorded in the rabbit wedge experiments. 
       This comprises the QT Percent Change at each concentration tested for each compound.

preparinginputdata.m is used with the input files pIC50_Values.dat and pIC50_Values_And_Hill_Coefficients.dat 
       to create the separate data files with compounds for which there is ion channel and rabbit 
       wedge data available for each assay, with one where just IC50 values and been fitted 
       (and the Hill Coefficient assumed to be 1) and one where both the IC50 value and 
       Hill Coefficient have been fitted. The files created are:-
		     - IonWorks_Data_Matrix.dat
		     - IonWorks_2Parameter_Data_Matrix.dat
		     - IonWorks_With_Iks_2Parameter_Data_Matrix.dat
		     - IonWorks_With_Iks_Data_Matrix.dat
		     - PatchXpress_2Parameter_Data_Matrix.dat
		     - PatchXpress_Data_Matrix.dat
		     - QSAR_Data_Matrix.dat

shannon_wang_puglisi_weber_bers_2004.cellml is the cellml file of the Shannon et al. 2004 model 
       used in the simulations.

The single cell and one dimensional simulations were run within Chaste, at revision number 18049. 

TestSingleCellWithOptions.hpp This runs the single cell simulations. 
      Code should first be compiled then run from the command line with
      options to specify which assay, which ion channels are assumed to be able to be blocked and how many
      parameters the ion channel data has been fit for. Options include:
          assay -assay_name (PatchXpress/IonWorks/QSAR)
          block -block_type (multiple/hERG)
          number_of_parameters -number_of_parameters_drug_block_model_is_fitted_for (1/2) 
              (IC50 Only or IC50 and Hill)
              include_KCNQ1 -whether_to_include_KCNQ1_interactions_when_using_IonWorks/FLIPR_data 
              (yes/no) (option only included when using IonWorks/FLIPR data)
      
      This file uses GeneralIonChannelDataReadIn.cpp and GeneralIonChannelDataReadIn.hpp to read in the ion
      channel data from the input data files. It continues simulation until steady state is reached, which is 				      
      controlled by SteadyState.cpp and SteadyState.hpp.
	
      A results folder for each compound is output with the % Change in APD90 at each concentration as 
      compared to that measured under control conditions recorded.

      The ode time step used for the results within the paper was 0.001. 
      Increasing the time step to 0.01 will maintain the level of accuracy needed for performing 
      these simulations and will increase the speed with which the simulations run.


Test1DSimulationWithDifferentTimeSteps.hpp This runs the one-dimensional simulations. 
    Code should first be compiled then run from the command line with options to specify 
    how many parameters the ion channel data has been fit for. This is specified using:
	    number_of_parameters -number_of_parameters_drug_block_model_is_fitted_for (1/2) (IC50 Only or IC50 and Hill)
	        	   
    This file uses GeneralIonChannelDataReadIn.cpp and GeneralIonChannelDataReadIn.hpp to 
    read in the ion channel data from the input data files. 
    PseudoECGReadIn.cpp and PseudoECGReadIn.hpp are used during post-processing in order to read in 
    the data for the pseudo ecg calculated so that the QT interval can be estimated.

    A results folder for each compound is output with the % Change in QT Interval at each concentration 
    as compared to that measured under control conditions recorded.

    The model equations are solved with different time steps over different portions of the propagating wave, 
    adjusted accordingly to the expected shape in each region so that only the necessary precision is used so
    to increase computational efficiency. Details of which time steps were used in which region can be 
    found within the comments in the code.    

calculatingmetricvalues.m is used to calculated the metric values from the output results files 
    from the single cell simulations when considering all the compounds for which there is data for each assay. 
    The name of the results file just needs to be input at the top of the file.

calculatingmetricvaluesforcommoncompounds.m is used to calculated the metric values from the output 
results files from the single cell simulations when considering only the 44 compounds for which there 
is data available for all assays. The name of the results file just needs to be input at the top of the file.

Common_PatchXpress_Data_Matrix.dat, Common_IonWorks_Data_Matrix.dat and Common_QSAR_Data_Matrix.dat 
    contain the names and ion channel data for these 44 compounds.

calculating1dmetricvalues.m is used to calculated the metric values from the output results files 
    from the one-dimensional simulations when considering all the compounds for which there is data for each assay. 
    The name of the results file just needs to be input at the top of the file.

calculating1dmetricvaluesforcommoncompounds.m is used to calculated the metric values from 
    the output results files from the one-dimensional simulations when considering only the 44 
    compounds for which there is data available for all assays. The name of the results file 
    just needs to be input at the top of the file. 
    Common_PatchXpress_Data_Matrix.dat, Common_IonWorks_Data_Matrix.dat and Common_QSAR_Data_Matrix.dat 
    contain the names and ion channel data for these 44 compounds.

plottingEC10plot.m is used to plot the four quadrant plot in Figure 2 for the quantitative 
    assessment of the predictivity of the model.