Main topics:

1. Introduction
2. System requirements
3. Installation
	3.1 Linux installation
4. Usage
	4.1 Data preparation for machine learning with VEGA ZZ
	4.2 Model generation with Weka
	4.3 Decision tree conversion
		4.3.1 Command line examples
	4.4 Graphic user interface
	4.5 Tree input file
5. C code description
	5.1 Constants
	5.2 Data types
	5.3 Shared global variables
	5.4 Functions
		5.4.1 Run information section
		5.4.2 Classifier model section
6. C++ code description
	6.1 Constants
	6.2 Model class
		6.2.1 Properties/Attributes
		6.2.2 Methods
	6.3 Usage
7. Fortran 90 code description
	7.1 Model module
		7.1.1 Constants
		7.1.2 Properties/attributes
		7.1.3 Methods
	7.2 Usage
8. Java code description
	8.1 Model class
		8.1.1 Constants
		8.1.2 Properties/attributes
		8.1.3 Methods
	8.2 Usage
9. JavaScript code description
	9.1 Model class
		9.1.1 Constants
		9.1.2 Properties/attributes
		9.1.3 Methods
	9.2 Usage
10. JScript code description
	10.1 Model pseudo-class
		10.1.1 Constants
		10.1.2 Properties/attributes
		10.1.3 Functions
	10.2 Usage
11. Lua code description
	11.1 Model class
		11.1.1 Constants
		11.1.2 Properties/attributes
		11.1.3 Methods
	11.2 Usage
12. PHP code description
	12.1 Model class
		12.1.1 Constants
		12.1.2 Properties/attributes
		12.1.3 Methods
	12.2 Usage
13. Python code description
	13.1 Model class
		13.1.1 Constants
		13.1.2 Properties/attributes
		13.1.3 Methods
	13.2 Usage
14. REBOL code description
	14.1 Model class
		14.1.1 Constants
		14.1.2 Properties/attributes
		14.1.3 Methods
	14.2 Usage
15. VBScript code description
	15.1 Constants
	15.2 Model class
		15.2.1 Properties/attributes
		15.2.2 Methods
	15.3 Usage
16. Examples & applications
	16.1 Prediction of blood-brain barrier permeation
		16.1.1 Usage
		16.1.2 About the decision tree model
	16.2 Prediction of mutagenicy
		16.2.1 Usage
		16.2.2 About the decision tree model
17. History
18. Copyright and disclaimers

 

1. Introduction

This program converts the machine learning models, in particular the classification trees, generated by Weka program mainly to C source code but it supports also other programming languages (e.g. C++, Fortran 90, Java, JavaScript, JScript, Lua, PHP, Python, REBOL and VBScript). The resulting code requires no or very limited modifications to be used. The program can recognize several molecular attributes/descriptors (especially those that are calculated by VEGA ZZ and MOPAC 2016) and it can add automatically the code to calculate them. Moreover, Tree2C can generate code also for the domain property check, which is a very useful feature to evaluate the confidence of the classification results. In addition, the program can build the code for different targets to be integrated in a pre-existing program:

• as generic C file with separated header;
• as monolithic header file;
• as C source code to build a dynamic link library for Windows (DLL), exporting the functions to call;
• as C-script to be used in VEGA ZZ program. When you run the resulting script, if the VEGA ZZ workspace is showing a structure, the classification is performed for the current molecule, otherwise a file requester is opened to select an input database of molecules. In this second case, the classification is performed for all molecules of the database.
• as C++ class with separated header;
• as Fortran 90 module;
• as Java class;
• as JavaScript class;
• as JScript pseudo-class;
• as Lua class;
• as PHP class in a single file;
• as Python 3 class module;
• as REBOL class;
• as VBScript class.

The code generated by Tree2C was successfully tested by different language compilers and interpreters as shown in the following table:

2. System requirements

Tree2C supports both Linux (x86 or x64) and Windows (2000/XP/Vista/7/8/8.1/10 x86 or x64) operating systems and requires the HyperDrive runtime library, which is the same used for VEGA ZZ software. Since the program is written in standard C code, it can be ported to other operating systems without modifications.

Tree2C is provided in two different versions:

• command line version (stand-alone);
• GUI version with graphic user interface integrated in VEGA ZZ environment.

Both versions shares the several features, but the GUI-based version supports only the C language as target.

3. Installation

Tree2C is provided in three different packages:

• Tree2C_X.X.X.zip
  This archive includes the command-line version of the program for Linux (x86 and x64) built by gcc and Windows (x86 and x64) built by Mingw32/64 and RAD Studio 10.2 Tokyo. Moreover, examples and scripts are provided only in this package and the GUI version of the program is not included.
   

• Vega_ZZ_X.X.X.X_Setup.exe
  This setup includes both command-line and GUI versions of Tree2C and the applicative examples (Prediction of blood-brain barrier permeation and Prediction of mutagenicy) ready to use.
   

• Vega_X.X.X.X_Linux_x86-x64-ARM.tar.gz
  This archive includes the command-line version of the program for Linux (x86 and x64) built by gcc. Windows and GUI versions are not provided as well as examples and scripts. 

The stand-alone version of Tree2C doesn't require the installation, while the GUI version is integrated in VEGA ZZ package and is installed automatically when you run the VEGA ZZ setup. Moreover, the same package includes the command line version (for both 32 and 64 bit Windows versions).

3.1 Linux installation

Linux systems require to set LD_LIBRARY_PATH environment variable to find the hdrive.so dynamic library. You can do it by editing your shell start-up script (e.g. .cshrc for csh or tcsh, .bashrc for GNU bash). For csh/tcsh shell, you must add these lines at the end of the script:

setenv LD_LIBRARY_PATH "<INSTALLATION_PATH> $LD_LIBRARY_PATH"
setenv PATH "<INSTALLATION_PATH>:$PATH"

where <INSTALLATION_PATH> is the directory in which Tree2C executable is present.

For sh/bash:

export LD_LIBRARY_PATH="<INSTALLATION_PATH> $LD_LIBRARY_PATH"
export PATH="<INSTALLATION_PATH>:$PATH"

For example, if you installed Tree2C for Linux in /usr/local/tree2c directory, you must set the environment variables (csh/tcsh):

setenv LD_LIBRARY_PATH "$/usr/local/tree2c $LD_LIBRARY_PATH"
setenv PATH "/usr/local/tree2c:$PATH"

or (sh/bash):

export VEGADIR="/usr/local/vega"
export LD_LIBRARY_PATH="/usr/local/vega $LD_LIBRARY_PATH"
export PATH="/usr/local/vega:$PATH"

Finally, you must change the file permissions:

chmod 755 tree2c

4. Usage

Before to use this utility, you must follow these steps in order obtain the code to perform the classification:

• preparation of the dataset to teach the learning algorithm;

• calculation of the attributes/descriptors;

• generation of the classification model by Weka;

• generation of the code by Tree2C.

This workflow is especially thought for the classification of molecules, but Tree2C can be used with success also with non-chemical datasets and models.

4.1 Data preparation for machine learning with VEGA ZZ

When you want to build a model to classify molecules, a training dataset of examples for each class is required in order to teach the learning algorithm. The so obtained model can be used to predict the belonging class of an unknown molecule as shown in the following scheme:

Obviously, to perform the classification, you must know the features/attributes of the query molecule and have the right tool to calculate them.
VEGA ZZ can help you in the first phase of this workflow and, in particular, it can be used not only to prepare the training set of molecules, but also to calculate several attributes. Its flexible database engine can help you in organizing and processing molecules from different data sources and formats (e.g. IUPAC name, use name, SMILES notation, InChI notation, 2D and 3D structures in different format, etc.) in order to obtain homogenous data ready to use for the calculation of the attributes as shown in the following scheme:

VEGA ZZ supports different types of databases, but when you have to perform the machine learning, it is very important the use of relational databases (e.g. Microsoft Access, MySQL, SQLite)  because 1) they can include not only the molecules structures but also their attributes and the belonging class; 2) you can manage the data not only with VEGA ZZ but also with other programs; 3) you can use the WarpEngine technology to calculate the descriptors (e.g. semi-empirical ones).
The generic procedure, which you can use to build a training set with VEGA ZZ, could be:

• Create and empty relational database (e.g. in Access format) by selecting the File Database Open item of main menu or clicking the Open button in the Database explorer window.

• Open the empty database in the Database explorer.

• Put the molecules into the database as explained here. When you add molecules to a relational database, VEGA ZZ calculates several properties that can be used as attributes for machine learning (look here for a complete list of the properties).

• If you want to calculate the Kier-Hall e-state descriptors, select File Run script in VEGA ZZ main menu, expand the tree at the Database level, choose Count functional groups.c script, and click the Run button. Select the database to process, in the message box, click No to store the descriptors in the same database and not a separated CSV file.

• If you want to calculate semi-empirical descriptors, you can use the MOPAC module of WarpEngine. The descriptors are saved into a CSV file and must be merged manually with the other ones by using a spreadsheet program.

• You can add other property columns from other data sources (e.g. Microsoft Excel) to the database by the clipboard: for example, copy a column of Excel and paste it to Edit tab of Database explorer clicking the Paste cols. button. During this operation, you must pay particular attention because 1) the column must have the label in the first row; 2) the number of items to paste must be the same of the molecules in the database; 3) the items must be in the same order of the molecules in the database to avoid misalignment errors. To overcome this last issue, you must remember that the molecules are alphabetically sorted in ascending order using the same algorithm implemented in Excel. So, if you sort the molecules in the same manner in Excel, you overcome this potential problem.

• Finally, you can extract the properties/attributes from the database in three different ways: 1) exporting them directly to Microsoft Excel clicking on the molecule list in Database explorer with the right mouse button and selecting Export to Excel, 2) exporting them to a file clicking as above, but selecting Export to file in the context menu; 3) making a query and exporting the data in your preferred front-end program for the database (e.g. Microsoft Access for mdb and accdb files).

4.2 Model generation with Weka

This part of the manual don't want to be exhaustive (this is only a "mini how-to" guide) and more information can be found in Weka manual and tutorials.

• Start Weka and choose Explorer as application.

• In Process tab, click Open file... and select the ARFF input file if you have it. This file can be prepared saving the data in CSV format from your preferred spreadsheet program (e.g. Microsoft Excel) and import it to Weka. In some cases, the imported file needs to be pre-processed (use the Edit button). More information on ARFF format (Attribute-Relation File Format) is available in Weka manual.

• Go to Classify tab and choose the classifier (press Choose button in Classifier box). For example, select RandomForrest in trees.

• In the options of the classifier (click on the classifier parameters of Classifier box), set printClassifiers option to True to generate the right output including the trees.

• Press Start button to generate the model.

• If the model is acceptable, save it by clicking with the right mouse button on Result list and choose Save result buffer. Put the file name adding .txt extension and press Save.

4.3 Decision tree conversion

If you run this utility by command prompt without arguments, the program options are shown as here below:

Tree2C V1.0.0 - (c) 2017-2023, Alessandro Pedretti

Usage: Tree2C INPUT_FILE -o[OUTPUT_FILE] -a[DATA_FILE] -i[SCRIPT_DIR]
              -l[CLASS_LABELS] -n[MODEL_NAME] -s[LANGUAGE]
              -t[TEMPLATE_DIR] -dfhmv

 a -> ARFF file to generate the domain check code
 d -> Add DLL code (define T2C_DLL to enable compiling the code)
 f -> Force to write the code also for the unused attributes
 h -> Save all code in the header file
 i -> Install the C-script in the specified directory
 l -> Class labels (comma separated)
 m -> Multi-language support (VEGA ZZ C-script only)
 n -> Name of the model (default input file name)
 o -> Output file name (default input file)
 s -> Target programming language:
      C (default), C++, Fortran90, Java, JavaScript, JScript, Lua,
      PHP, Python, REBOL, VBScript
 t -> VEGA template directory (usually autodetected)
 v -> Code compatible with VEGA ZZ C-script

Examples:
Tree2C weka_tree.txt
Tree2C weka_tree.txt -s Python
Tree2C weka_tree.txt -l "No,Yes"
Tree2C weka_tree.txt -o prediction.c -a weka_input.arff -v

All parameters are optional with the exception of the the input file (INPUT_FILE), which includes the decision tree model generated as explained in the previous section. The meaning of the other parameters is summarized in the following table:

*All options are case-insensitive.

4.3.1 Command line examples

Here are some examples to clarify the use of Tree2C:

• tree2c weka_tree.txt
  This command generates both weka_tree.c and weka_tree.h files.
   
• tree2c weka_tree.txt -s python
  This example generates the code for Python 3.
   
• tree2c weka_tree.txt -l "No,Yes"
  As above, but in this case uses No and Yes as labels of the two classes instead of 0 and 1.
   
• tree2c weka_tree.txt -o prediction.c -a weka_input.arff -v
  In this example, a C-script for VEGA ZZ is generated including the code for the domain check.

Here, the typical Tree2C output of a generic run is shown:

tree2c "random tree.txt"

* Loading the model

  Target programming language..: C
  Original model name..........: RANDOM_TREE
  Model name for the code......: RANDOM_TREE
  Number of attributes.........: 58
  Number of unused attributes..: 31
  Unused attributes............: Surface Charge FG_Br FG_CHO FG_CN3 FG_CNH FG_CNR
  Number of trees..............: 1
  Number of output values......: 2
  Class values.................: FALSE TRUE
  Class labels.................: None

* Saving the C code
* Done

4.4 Graphic user interface

To use the GUI version of Tree2C, you must start VEGA ZZ and select File Run script in the main menu. Hence, you must find Development tools Decision tree to C converter.vll in the script tree and finally you must double click on it. Although the program is managed as a VEGA ZZ C-script, you cannot edit the source code because it was built as VEGA Link Library (VLL), which is in binary format. As for the standard C-scripts, you can show the help clicking the > symbol on the right side of the Select the script ... window.

The features of this Tree2C version are the same of the command line version but are accessible through a nice graphic user interface. To build the C code (the only language supported by this version), you must:

• Select the input text file with the tree in Weka tree model.
• Optionally, you can choose also the ARFF (ARFF file field) file used to generate the model to generate the code to check if the calculated attributes are included in the classification domain defined as range of the properties used to build the model.
• Set the output file name (Output C file).
• You can specify the name of the model if the proposed one is not satisfactory (see Model name field).
• Optionally, you can specify the labels printed as output for each class (Class labels field). The labels must be comma separated and their number must be the same of number of classes detected by the model.
• Select the source code type to generate. More in detail you can choose:
  - VEGA ZZ C-script
  - C source + header
  - Header only
• If you are building a VEGA ZZ C-script and you want to install it into VEGA ZZ environment, you can check Install VEGA ZZ C-Script and put the installation directory in Script directory field. If you leave this field empty, the C-Script will be installed in home directory of the scripts. You can use the disk button to explore the directory tree and you must remember you cannot install scripts outside the directory tree of the scripts.
• Finally, click the Convert button.

4.5 Tree input file

As explained above, the input file required by Tree2C is the output generated by Weka when you run a tree-based classifier (random tree, random forest, etc.), but since is a text file, you can generate it in easy way by other programs. This paragraph doesn't want to be an exhaustive guide on the Weka output format, but shows only the most important topics aimed to build a file compatible with Tree2C.
The file includes three parts: 1) a header with the information on the attributes and the learning approach (Run information section); 2) one or more decision trees (Classifier model section); 3) a footer with the statistical data (Summary section). Tree2C requires only the first two sections of the file.

4.5.1 Run information section

Not all tags of this section are needed by Tree2C and, in particular, only the first two must be always present: Scheme and Attributes.

• Scheme
  It is used by the program to recognize the file and to detect the type of the model. At this time, only classification trees are supported and so this tag must assume weka.classifiers.trees value. Weka reports also the type of the tree and the parameters used for its generation, but since Tree2C ignores this information, you can omit them. So the typical value of Scheme can be:

Scheme:       weka.classifiers.trees.RandomTree -K 0 -M 1.0 -V 0.001 -S 1

and the minimal value of Scheme for Tree2C is:

Scheme:       weka.classifiers.trees

• Attributes
  This tag reports the number of attributes and optionally their list. Here it is shown a typical example generated by Weka with the list of the attributes when the number of attributes is less than 100:

Attributes:   5
              Angles
              Atoms
              Dipole
              HbAcc
              HbDon

Since Tree2C can find the attributes directly from the trees, you cannot specify their list as shown below:

Attributes:   5
              [list of attributes omitted]

The Run information label cannot be present because Tree2C assumes by default that the first section found in the file is just this one.

4.5.2 Classifier model section

The Classifier model label marks the section in which one ore more decision trees are reported. This label is optional for Tree2C because it searches directly for the RandomTree label, which denotes the beginning of each tree. The tree is drawn from left to right and the splitting nodes are not indicated but are placed virtually in the middle of the segment built by multiple pipe characters ( | ). At the end of two branches of the fork there is a leaf represented by an attribute and a condition (respectively the true and false conditions for each leaf pair) as shown below:

Attribute1 < Value1
|
| Other branches
|
Attribute1 >= Value1
|
| Other branches

The previous example shows the comparison of an attribute (Attribute1) with a threshold value (Value1) through a pair of operators (less than and equal or greater than) for both true and false conditions. Just for an exemplification, the corresponding pseudo-code is:

if Attribute1 < Value1 then
    True condition
else
    False condition

If you have to insert a branch with a Boolean attribute, you must use a different representation as shown below:

Attribute2 = yes
|
| Other branches
|
Attribute2 = no
|
| Other branches

and the corresponding pseudo code is:

 if Attribute2 is true then
    True condition
else
    False condition

When a leaf must return the class and you don't have to continue the tree with other branches, you can indicate the class after the condition as shown in the following example:

Attribute3 < Value3 : 1
Attribute3 >= Value3 : 0

where 0 and 1 are the class IDs. Translating the node to pseudo-code:

 if Attribute3 > Value3 then
    return 1
else
    return 0

Weka adds statistical data (two integer numbers separated by a slash) to this kind of leaf, which is however ignored by Tree2C:

Attribute3 < Value3 : 1 (TotInst/MissClassInst)
Attribute3 >= Value3 : 0 (TotInst/MissClassInst)

In particular, the first number is the total number of instances (TotInst, weight of instances) reaching the leaf and the second number is the number (weight) of those instances that are misclassified (MIssClassInst).

5. C code description

All constants, data structures and functions are named according to the rule in which each object has T2C_MODEL_NAME_ prefix, where MODEL_NAME is obtained automatically from the Weka file name capitalizing it and replacing the spaces with underscores characters ("_") or is specified by the user with -n option.

5.1 Constants

The constants are defined in the header file or in the C file if you have selected an output without header file.

• Output classes
  They are the values for each class returned by the classification function T2C_MODEL_NAME_Classify(). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

/**** Output values ****/

#define T2C_RANDOM_TREE_FALSE                   0
#define T2C_RANDOM_TREE_TRUE                    1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants whose prefix is T2C_MODEL_NAME_ATTRIBUTE_NAME_ followed respectively by NO and YES for a better readability of the source code.
  
  Example:

/**** Values of the attributes ****/

#define T2C_RANDOM_TREE_FG_CON2_NO              0
#define T2C_RANDOM_TREE_FG_CON2_YES             1

• MOPAC constants
  If Tree2C detects attributes/properties whose calculation requires MOPAC, additional constants are added in the code. In particular, T2C_MOPAC_KEYS specifies the parameters required for the calculation of the parameters and, by default, includes PM7 GEO-OK MMOK 1SCF keywords. If the program detects parameters that need the calculation of the superdelocalizability, the SUPER keyword is automatically added. These default keyword implies that the molecule structures for which you want to perform the classification, are already optimized, but if this condition is not true, you can remove the 1SCF keyword. For more information, you can consult the MOPAC manual. Constants to enumerate MOPAC properties are also added as T2C_MOPAC_PROPERTY_NAME as well as the T2C_MOPAC_NUM_OF_PROPERTIES constants to indicate the total number of MOPAC properties, which is used to give the right dimension of MopacProp global vector.
  
  Example:

/**** MOPAC keywords ****/

#define T2C_MOPAC_KEYS                          "PM7 GEO-OK MMOK 1SCF SUPER"

/**** MOPAC properties ****/

#define T2C_MOPAC_CORE_CORE_REPULSION           0
#define T2C_MOPAC_COSMO_AREA                    1
#define T2C_MOPAC_COSMO_VOLUME                  2
#define T2C_MOPAC_DE_TOTAL                      3
#define T2C_MOPAC_DN_TOTAL                      4
#define T2C_MOPAC_DIPOLE                        5
#define T2C_MOPAC_ELECTRONIC_ENERGY             6
#define T2C_MOPAC_HEAT_OF_FORMATION             7
#define T2C_MOPAC_HOMO_ENERGY                   8
#define T2C_MOPAC_IONIZATION_POTENTIAL          9
#define T2C_MOPAC_LUMO_ENERGY                   10
#define T2C_MOPAC_MULLIKEN_ELECTRONEGATIVITY    11
#define T2C_MOPAC_NO_OF_FILLED_LEVELS           12
#define T2C_MOPAC_PARR_POPLE_ABSOLUTE_HARDNESS  13
#define T2C_MOPAC_PIS_TOTAL                     14
#define T2C_MOPAC_SCHUURMANN_MO_SHIFT_ALPHA     15
#define T2C_MOPAC_TOTAL_ENERGY                  16

#define T2C_MOPAC_NUM_OF_PROPERTIES             17

• C-script related constants
  Some constants are added to the source code only if you are building a C-script (see -v option) to set graphical parameters of the window shown to abort the calculation when you are managing a library of molecules:
   

  Constant	Description
  T2C_ABWWIDTH	Width of the abort window.
  T2C_ABWHEIGHT	Height of the abort window.
  T2C_BTWIDTH	Width of the abort button.
  T2C_BTHEIGHT	Height of the abort button.

  Example:

/**** Window parameters ****/

#define T2C_ABWWIDTH     300    /* Abort window width  */
#define T2C_ABWHEIGHT    104    /* Abort window height */
#define T2C_BTWIDTH       89    /* Button width        */
#define T2C_BTHEIGHT      25    /* Button height       */

5.2 Data types

The only data type defined in the source code is that is used as input for both T2C_MODEL_NAME_Classify() and T2C_MODEL_NAME_DomCheck() functions. It is named T2C_MODEL_NAME_INPUT and in its structure, the Boolean and discrete attributes/parameters are defined respectively as integer numbers (int type) and the other ones as single precision floating point numbers (float type).

Example:

/**** Data types ****/

typedef struct {
  float    Angles;
  float    Atoms;
  float    Bonds;
  float    ChiralAtms;
  float    Dipole;
  float    EzBnds;
  int      FG_CON2;
  int      FG_COOH;
  int      FG_COOR;
  int      FG_F;
  int      FG_PhOH;
  float    FlexTorsions;
  float    Gyrrad;
  float    HbAcc;
  float    HbDon;
  float    HeavyAtoms;
  float    Lipole;
  float    Mass;
  float    Ovality;
  float    Psa;
  float    Rings;
  float    Sas;
  float    Sav;
  float    Sdiam;
  float    Torsions;
  float    Vdiam;
  float    VirtualLogP;
} T2C_RANDOM_TREE_INPUT;

5.3 Shared global variables

Tree2C declares several shared global variables for the C-scripts as shown in the following table:

5.4 Functions

Here you can find the description of each C function generated by Tree2C.

• int T2C_MODEL_NAME_Classify(T2C_MODEL_NAME_INPUT *Input)
  This function is always present in the code generated by Tree2C and performs the classification according to the attributes included in T2C_MODEL_NAME_INPUT structure.
   

  Parameters:
  Input		Attributes/descriptors needed for the classification that must be pre-calculated.

  Return values:
  This function returns the class as integer number (usually 0 and 1) according to the given input data.

• int T2C_MODEL_NAME_DomCheck(T2C_SUPER_INPUT *Input)
  The code of this function is generated only If you used the -a option to specify the ARFF by which the classification model was created. Calling this function, you can check if the attributes used for the prediction are in the same domain of those used to build the model.
   

  Parameters:
  Input		Attributes/descriptors needed for the classification that must be pre-calculated.

  Return values:
  This function returns the number of domain violations, which is a measure of the reliability of data: the higher number of violations, the lower the reliability of the prediction. It ranges from 0 (= no violations) to the total number of the attributes included in the classification model (= lowest reliability of data).

Here is the list of the specific function for C-scripts. Some of them uses GraphAppZ and HyperDrive data types that are defined respectively in graphappz.h and hdtype.h header files that are stored in ...\VEGA ZZ\Tcc\include\vega and ...\VEGA ZZ\Tcc\include\hyperdrive directory. If you installed the 64 bit version of VEGA ZZ, the Tcc directory is renamed to Tcc64.

• HD_VOID BT_AbortClick(GAZ_BUTTON b)
  This is the function used to manage the event (click on abort button) to stop the classification the molecules included in a library.
   

  Parameters:
  b		Handle of the button generating the event.

  Return values:
  This function doesn't return any value.

• HD_LONG HD_CALLBACK CalcThread(HD_VOID *Arg)
  This function is called to run the classification in asynchronous non-blocking way by HD_MthCreateThread() implemented in HyperDrive library.
   

  Parameters:
  Arg		Pointer to user data used by the thread that, in this case, is set to NULL.

  Return values:
  This function returns a non-zero value if an error occurs.

• HD_VOID Error(const HD_CHAR *Err)
  It shows an error message.
   

  Parameters:
  Err		Pointer to the C string with the error message.

  Return values:
  This function doesn't return any value.

  
   

• HD_BOOL MopacRun(HD_PROC hProc, const HD_CHAR *MopacKeys)
  This function runs MOPAC and fills the MopacProp vector with semi-empirical descriptors derived from the calculation.
   

  Parameters:
  hProc		Handle of the process created with HD_ProcNew() of HyperDrive library.
  MopacKeys		MOPAC keywords to control the calculation (see T2C_MOPAC_KEYS constants).

  Return values:
  Return values can be 1 if no error occurs, or 0 if the function fails.

• HD_BOOL T2C_MODEL_NAME_ClassifyMol(HD_LONG *Class, HD_LONG *Violations, HD_ATOM *Atm, HD_ULONG TotAtm)
  This function is present in the source code if you built a C-script and performs the classification of a molecule calculating all needed attributes. From the point of view of the implementation, it calls T2C_MODEL_NAME_DomCheck() and T2C_MODEL_NAME_Classify() before the attribute calculation, which is performed calling in turn functions of VEGA and HyperDrive library as well as performing a MOPAC calculation. You don't need to call manually this function, because the C-script includes all code to to prepare the required input for both CalcThread() (for the classification of a library of molecules) and VllMain() (for the classification of a single molecule) functions.
   

  Parameters:
  Class		Pointer to the integer in which the function returns the predicted class.
  Violations		Pointer to the integer in which the function returns the number of the domain violations.
  Atm		Pointer of the first element of the atom list according to the VEGA convention.
  TotAtm		Total number of the atoms of the molecule to which you want to perform the classification.

  Return values:
  Return values can be 1 if no error occurs, or 0 if the function fails.

• float VegaGetAtt(const HD_CHAR *Att)
  VegaGetAtt() retrieve/calculate an attribute through VEGA ZZ interface by Get command.
   

  Parameters:
  Att		Attribute/descriptor name.

  Return values:
  This function returns the calculated value as floating point number.

6. C++ code description

When you select C++ as output, Tree2C generates two files: the header and the code files. The former includes the definition of the class which is named according to T2CPP_MODEL_NAME rule and the latter includes the code of the methods. Tree2C is unable to generate the C++ code to calculate the attributes/parameters when you specify the -v option.
 

6.1 Constants

The constants are defined in the header file as for the C output.

6.2 Model class

The model class includes properties and methods to perform the classification in easy way and is defined as in the following example:

/**** Class definition ****/

class T2CPP_RANDOM_TREE
{
  public:

6.2.1 Properties/attributes

The properties are defined in the header file as shown in the following example:

/**** Properties ****/

float    Angles;
float    Atoms;
int      FG_CON2;

6.2.2 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them.

• Classify()
  It performs the prediction and return the belonging class.
   
• DomCheck()
  It checks if the attributes used for the prediction are in the same domain of those used to build the model. It returns the number of domain violations, which is a measure of the reliability of data: the higher number of violations, the lower the reliability of the prediction. It ranges from 0 (= no violations) to the total number of the attributes included in the classification model (= lowest reliability of data).

6.3 Usage

Before to use the class, you must create the related object:

T2CPP_RANDOM_TREE     Model;

then, you must set the properties:

Model.Angles       = 325.0f;
Model.Atoms        = 176.0f;
Model.FG_CON2      = 0;

finally, you must call the methods:

printf("Domain violations: %d\n", Model.DomCheck());
printf("Predicted class: %d\n", Model.Classify());

The resources of Model object are automatically freed exiting by the function and/or the compound. The object can be also created dynamically by new command:

T2CPP_RANDOM_TREE *   Model = new T2CPP_RANDOM_TREE();

but since new returns the pointer to the object, the syntax required to address properties and methods is different and, in particular, for the properties:

Model -> Angles       = 325.0f;
Model -> Atoms        = 176.0f;
Model -> FG_CON2      = 0;

and for the methods:

printf("Domain violations: %d\n", Model -> DomCheck());
printf("Predicted class: %d\n", Model -> Classify());

The resources of the objects created by new aren't not automatically released and, therefore, you must free them by delete command:

delete Model;

7. Fortran 90 code description

When you select Fortran90 as output, the class/module is named according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the Fortran 90 code to calculate the attributes/parameters when you specify the -v option.

7.1 Model module

The model module includes constants, properties and methods to perform the classification in easy way and is defined as in the following example:

!**** Classification module ****/

module random_tree
  implicit none

7.1.1 Constants

The constants have T2F90_MODEL_NAME_ prefix and are defined inside the module as parameters:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

  !**** Output values ****

  integer, parameter :: T2F90_RANDOM_TREE_FALSE = 0
  integer, parameter :: T2F90_RANDOM_TREE_TRUE = 1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

  !**** Values of the attributes ****

  integer, parameter :: T2F90_RANDOM_TREE_FG_CON2_NO = 0
  integer, parameter :: T2F90_RANDOM_TREE_FG_CON2_YES = 1

7.1.2 Properties/attributes

The properties are declared inside a type definition whose name is T2F90_MODEL_NAME_Input as shown in the following example:

  type :: T2F90_RANDOM_TREE_Input

    !**** Properties ****

    real :: Angles
    real :: Atoms
    integer :: FG_CON2

The type definition is closed by the declaration of the methods to perform the classification (Classify) and the domain check (DomCheck):

  contains
    procedure, pass(this) :: Classify
    procedure, pass(this) :: DomCheck
  end type T2F90_RANDOM_TREE_Input

7.1.3 Methods

Tree2C generates the code for two methods Classify and, optionally when you specify the ARFF file with -a option, DomCheck. Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

7.2 Usage

First of all, after the program declaration, you must include the module code:

program random_tree_test
  use random_tree
  implicit none

before to use the class, you must create the related object:

  type(T2F90_RANDOM_TREE_Input) :: Model

then, you must set the properties:

  Model%Angles = 325
  Model%Atoms = 176
  Model%FG_CON2 = 0

and now you can call the methods:

  print *, " Domain violations: ", Model%DomCheck()
  print *, " Predicted class: ", Model%Classify()

finally, you must remember to add the following line to end the program:

  end program random_tree_test

8. Java code description

When you select Java as output, the class is named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the Java code to calculate the attributes/parameters when you specify the -v option.

8.1 Model class

The model class includes constants, properties and methods to perform the classification in easy way and is defined as in the following example:

/**** Model class ****/

class random_tree {

8.1.1 Constants

The constants have C_ prefix and are defined inside the class as static final properties (constants):

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

  /**** Output values ****/

  static final int C_FALSE = 0;
  static final int C_TRUE = 1;

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

  /**** Values of the attributes ****/

  static final int C_FG_CON2_NO = 0;
  static final int C_FG_CON2_YES = 1;

8.1.2 Properties/attributes

The properties are declared inside the class as shown in the following example:

  /**** Attributes ****/

  float Angles;
  float Atoms;
  int FG_CON2;

8.1.3 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

8.2 Usage

First of all, after the program and main class declaration, you create the object of the class:

public class random_tree_test
{
  public static void main(String[] args)
  {
    random_tree Model = new random_tree();

then, you must set the properties:

  Model.Angles = 325.0f;
  Model.Atoms = 176.0f;
  Model.FG_CON2 = 0;

and now you can call the methods:

  System.out.printf(" Domain violations: %d\n", Model.DomCheck());
  System.out.printf(" Predicted class: %d\n", Model.Classify());

finally, you must remember to add the following lines to end the program:

  }
}

9. JavaScript code description

When you select JavaScript as output, the class is named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the JavaScript code to calculate the attributes/parameters when you specify the -v option.

9.1 Model class

The model class includes constants, properties and methods to perform the classification in easy way and is defined as in the following example:

/**** Model class ****/

class random_tree {

9.1.1 Constants

The constants (this is an improper term, because in JavaScript the constant type doesn't exist) have C_ prefix and are defined inside the constructor of the class:

  /**** Constructor ****/

  constructor() {

There are two type of constants:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

    /**** Output values ****/

    this.C_FALSE = 0;
    this.C_TRUE = 1;

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

    /**** Values of the attributes ****/

    this.C_FG_CON2_NO = 0;
    this.C_FG_CON2_YES = 1;

9.1.2 Properties/attributes

The properties are declared inside the class constructor and are initialized to zero as shown in the following example:

    /**** Attributes ****/

    this.Angles = 0.0;
    this.Atoms = 0.0;
    this.FG_CON2 = 0;

9.1.3 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

9.2 Usage

First of all, you must include the code of the classification class. The following example is based on Node.js but the syntax can differ on the basis of the JavaScript interpreter:

const random_tree = require('./random_tree.js');

before to use the class, you must create the related object:

  const Model = new random_tree();

and now you must set the properties:

  Model.Angles = 325.0;
  Model.Atoms = 176.0;
  Model.FG_CON2 = 0;

finally, you can call the methods:

  console.log(" Domain violations: %d", Model.DomCheck());
  console.log(" Predicted class: %d", Model.Classify());

10. JScript code description

JScript is Microsoft's dialect of ECMAScript standard and although shares some programming and syntax paradigms with JavaScript, it must not confused with JavaScript. JScript doesn't support class programming, but it is possible to implement pseudo-classes through functions.
When you select JScript as output, a pseudo-class is created as a function named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the JScript code to calculate the attributes/parameters when you specify the -v option.

10.1 Model pseudo-class

The model class includes constants, properties and methods to perform the classification in easy way and is defined as in the following example:

/**** Model pseudo-class ****/

function random_tree() {

10.1.1 Constants

As for JavaScript, the constants are not supported by JScript, but Tree2C creates the code declaring and initializing variables according to the rule in which each variable is preceded by the C_ prefix. They are defined at the beginning of the main function and there are two type of constants:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

    /**** Output values ****/

    this.C_FALSE = 0;
    this.C_TRUE = 1;

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

    /**** Values of the attributes ****/

    this.C_FG_CON2_NO = 0;
    this.C_FG_CON2_YES = 1;

10.1.2 Properties/attributes

The properties are declared inside the main function and are initialized to zero as shown in the following example:

    /**** Attributes ****/

    this.Angles = 0.0;
    this.Atoms = 0.0;
    this.FG_CON2 = 0;

10.1.3 Functions

Tree2C generates the code for two functions inside the main function, namely Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both functions can be managed as methods and don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two functions, click here.

10.2 Usage

As first step, you must include the code of the classification function.

<job>
  <script language="JScript" src="random_tree_jscript.js"/>
  <script language="JScript">

before to use the external function, you must create the related object:

    var Model = new random_tree();

then, you must set the properties:

    Model.Angles = 325.0;
    Model.Atoms = 176.0;
    Model.FG_CON2 = 0;

finally, you can call the methods:

    WSH.echo("Domain violations:", Model.DomCheck(),
             "Predicted class:  ", Model.Classify());

finally, you must remember to add the following lines to end the script:

  </script>
</job>

11. Lua code description

When you select Lua as output, Tree2C generates the the class code for you, which is a little bit tricky if you want to write it by yourself. As usual, the class is named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the Lua code to calculate the attributes/parameters when you specify the -v option.

11.1 Model class

As explained above, all code to declare the class is automatically generated by Tree2C as shown in the following example:

---- Model class ----

random_tree = {}
random_tree.__index = random_tree

11.1.1 Constants

Also for Lua, the constants are not supported and are replaced by standard properties which, however, are not write-protected as the constants. This kind of properties, have C_ prefix and are defined inside the constructor of the class:

function random_tree:New()
  local Acnt = {}
  setmetatable(Acnt, random_tree)

There are two type of constants:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

  ---- Output values ----

  self.C_FALSE = 0
  self.C_TRUE = 1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

    /**** Values of the attributes ****/

    this.C_FG_CON2_NO = 0;
    this.C_FG_CON2_YES = 1;

11.1.2 Properties/attributes

The properties are declared inside the class constructor and are initialized to zero as shown in the following example:

  ---- Properties ----

  self.Angles = 0.0
  self.Atoms = 0.0
  self.FG_CON2 = 0

11.1.3 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

11.2 Usage

First of all, you must include the code of the classification class:

require 'random_tree'

before to use the class, you must create the related object:

Model = random_tree:New()

then, you must set the properties:

Model.Angles = 325
Model.Atoms = 176
Model.FG_CON2 = 0

finally, you can call the methods:

print(" Domain violations: " .. Model:DomCheck())
print(" Predicted class: " .. Model:Classify())

12. PHP code description

When you select PHP as output, the class is named (in upper case) according to the name of the model in Weka file or by -n option preceded by T2PHP_ prefix. Tree2C is unable to generate the PHP code to calculate the attributes/parameters when you specify the -v option.

12.1 Model class

The model class includes constants, properties and methods to perform the classification in easy way and is defined as in the following example::

/**** Model class ****/

class T2PHP_RANDOM_TREE {

12.1.1 Constants

There are two type of constants, which are declared inside the class and  have C_ prefix:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

  /**** Output values ****/

  const C_FALSE = 0;
  const C_TRUE = 1;

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

  /**** Values of the attributes ****/

  const C_FG_CON2_NO = 0;
  const C_FG_CON2_YES = 1;

12.1.2 Properties/attributes

The properties are declared inside the class constructor and are initialized to zero as shown in the following example:

  /**** Properties ****/

  public $Angles = 0.0;
  public $Atoms = 0.0;
  public $FG_CON2 = 0;

12.1.3 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

12.2 Usage

First of all, you must include the code of the classification class:

<?php
  require 'random_tree.php';

before to use the class, you must create the related object:

  $Model = new T2PHP_RANDOM_TREE();

then, you must set the properties:

  $Model -> Angles = 325;
  $Model -> Atoms = 176;
  $Model -> FG_CON2 = 0;

and now you can call the methods:

echo " Domain violations: " . $Model -> DomCheck() . "\n";
echo " Predicted class: " . $Model -> Classify() . "\n";

finally, you must remember to add the following line to end the script:

?>

13. Python code description

The code generated by Tree2C is compatible only with Python 3 and Python 2.7 is not currently supported. More in detail, as for the C code, the class is named as T2PY_MODEL_NAME. Although VEGA ZZ supports Python for scripting, at this time, Tree2C is unable to generate the code to calculate the attributes/parameters when you use the -v option.

13.1 Model class

The model class includes the properties/attributes and the methods to perform the classification and the domain check in easy way and is defined as in the following example:

#**** Model class ****

class T2PY_RANDOM_TREE:

13.1.1 Constants

Unlike the C language, which supports constants values through the macro pre-processor, Python doesn't have this feature and hence the constants are defined as standard properties inside the class of the classifier.

• Output classes
  They are the values for each class returned by the classification method (Classify()). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

#**** Output values ****

C_FALSE = 0
C_TRUE = 1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with variables whose prefix is C_ATTRIBUTE_NAME_ followed respectively by NO and YES for a better readability of the source code.
  
  Example:

#**** Values of the attributes ****

C_FG_CON2_NO = 0
C_FG_CON2_YES = 1

13.1.2 Properties/attributes

Although Python doesn't require to declare the properties, it was preferred initialize all attributes to 0 in order to provide a list of those that are effectively used in the model, making easier the code writing to pass the values. Example:

#**** Properties ****

Angles = 0.0
Atoms = 0.0
FG_CON2 = 0

13.1.3 Methods

Tree2C generates the code for two methods Classify() and, optionally when you specify the ARFF file with -a option, DomCheck(). For more information, see the C++ version.

13.2 Usage

First of all, you must include the code of the classification class:

import random_tree

before to use the class, you must create the related object:

Model = random_tree.T2PY_RANDOM_TREE()

then, you must set the properties:

Model.Angles = 325
Model.Atoms = 176
Model.FG_CON2 = 0

finally, you can call the methods:

print(" Domain violations:", Model.DomCheck())
print(" Predicted class: ", Model.Classify())

14. REBOL code description

When you select REBOL as output, the class is named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the REBOL code to calculate the attributes/parameters when you specify the -v option.

14.1 Model class

The model class includes constants, properties and methods to perform the classification in easy way and is defined as in the following example::

REBOL [
  Title: "random_tree"
  File: %random_tree.r
]


;**** Model class ****

random_tree: make object! [

14.1.1 Constants

REBOL doesn't support constants, which therefore are implemented as normal class properties. There are two type of constants, which are declared inside the class and  have C_ prefix:

• Output classes
  They are the values of each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

  ;**** Output values ****

  C_FALSE: 0
  C_TRUE: 1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

;**** Values of the attributes ****

C_FG_CON2_NO: 0
C_FG_CON2_YES: 1

14.1.2 Properties/attributes

The properties are declared inside the class and are initialized to zero as shown in the following example:

  ;**** Properties ****

  Angles: 0.0
  Atoms: 0.0
  FG_CON2: 0

14.1.3 Methods

Tree2C generates the code for two methods Classify and, optionally when you specify the ARFF file with -a option, DomCheck. Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

14.2 Usage

First of all, you must include the code of the classification class:

REBOL [
  Title: "random_tree_test"
  File: %random_tree_test.r
]

do %random_tree.r

the object don't need to be created and you can set directly the properties:

random_tree/Angles: 325.0
random_tree/Atoms: 176.0
random_tree/FG_CON2: 0

and now you can call the methods:

print [" Domain violations: " random_tree/DomCheck]
print [" Predicted class: " random_tree/Classify "]

15. VBScript code description

When you select VBScript as output, the class is named (in lower case) according to the name of the model in Weka file or by -n option. Tree2C is unable to generate the VBScript code to calculate the attributes/parameters when you specify the -v option.

15.1 Constants

There are two type of constants, which are declared with T2VBS_MODEL_NAME_ prefix:

• Output classes
  They are the values for each class returned by the classification method (Classify). Their names are defined by -l option, otherwise TRUE and FALSE are used as default.
  
  Example:

'**** Output values ****

const T2VBS_RANDOM_TREE_FALSE = 0
const T2VBS_RANDOM_TREE_TRUE = 1

• Boolean values for the attributes
  For the attributes including only Boolean values, Tree2C replaces 0 and 1 values with constants (parameters) variables whose prefix is the same explained above followed respectively by NO and YES for a better readability of the source code.
  
  Example:

'**** Values of the attributes ****

const T2VBS_RANDOM_TREE_FG_CON2_NO = 0
const T2VBS_RANDOM_TREE_FG_CON2_YES = 1

15.2 Model class

The model class includes properties and methods to perform the classification in easy way and is defined as in the following example::

'**** Model class ****

Class random_tree

15.2.1 Properties/attributes

The properties are declared inside the class and to avoid conflicts with VBS keywords, the Attr suffix is added to the name as shown in the following example:

  '**** Attributes ****

  Public AnglesAttr
  Public AtomsAttr
  Public FG_CON2Attr

15.2.2 Methods

Tree2C generates the code for two methods Classify and, optionally when you specify the ARFF file with -a option, DomCheck. Both methods don't have arguments because the data is taken from the attribute properties that must be set before to call them. For more information on these two methods, click here.

15.3 Usage

As first step, you must include the code of the classification function.

<job>
  <script language="VBScript" src="random_tree.vbs"/>
  <script language="VBScript">

before to use the external function, you must create the related object:

    Dim Model
    Set Model = New random_tree

then, you must set the properties:

    Model.AnglesAttr = 325.0
    Model.AtomsAttr = 176.0
    Model.FG_CON2Attr = 0

finally, you can call the methods:

    WScript.Echo "Domain violations:", Model.DomCheck(), vbNewLine, _
                 "Predicted class: ", Model.Classify()

finally, you must remember to add the following lines to end the script:

  </script>
</job>

16. Examples & applications

16.1 Prediction of blood-brain barrier permeation

This is an example of a C-script generated automatically by Tree2C and performs the classification of molecules between permeants and non-permeants of blood-brain barrier (BBB) through a decision tree. Since the attributes are calculated by VEGA ZZ, no additional code was written manually. This script is included in VEGA ZZ package and you can run it selecting File Run script in VEGA ZZ main menu and double clicking BBB permeation predictor.c in ADMET.

16.1.1 Usage

If a molecule is present in the current workspace, a single classification is performed, otherwise a file requester is shown to select an input database. In this case, the classification is performed for all molecules of the database and the results are saved to a CSV file.
Since the training set used in the learning phase to build the model includes molecules is in neutral form, also the molecules for which you want to predict the BBB permeation must be in this form.

16.1.2 About the decision tree model

To derive the model, the Li's dataset (J. Chem. Inf. Model., 2005, 45, 1376-1384) was used as learning set with Weka 3.8 software. All molecules were converted from SMILES to 3D by VEGA ZZ and optimized by MOPAC 2016 (PM7 PRECISE GEO-OK SUPER keywords), keeping them in neutral form. 129 properties/attributes were calculated by both VEGA ZZ and MOPAC 2016. The most significant attributes were selected according to the BestFirst search algorithm (direction = Forward; lookupCacheSize = 1; searchTermination = 5) and the WrapperSubsetEval attribute evaluator (classifier = RandomForest with default settings; doNotCheckCapabilities = False; evaluationMeasure = accuracy, RMSE; folds = 5; seed = 1; threshold = 0.01) as implemented in Weka. In this way, only 9 attributes were kept, namely:

Charge attribute appears in the list because the learning set includes quaternary ammonic molecules that were not neutralized with a counter ion. All electronic descriptor calculated by MOPAC 2016 with SUPER keyword were considered not meaningful by the selection algorithm to be considered in the next phase.
The final model was obtained by Random Forest machine learning algorithm implemented in Weka with default parameters (bagging with 100 iterations and base learner) and performing a 10 fold cross-validation. The results are summarized below, where class 0 and 1 indicate non-permenat and permeant molecules:

=== Stratified cross-validation ===
=== Summary ===

Correctly Classified Instances         346               83.3735 %
Incorrectly Classified Instances        69               16.6265 %
Kappa statistic                          0.6179
Mean absolute error                      0.2655
Root mean squared error                  0.3647
Relative absolute error                 59.5558 %
Root relative squared error             77.2667 %
Total Number of Instances              415

=== Detailed Accuracy By Class ===

                 TP Rate  FP Rate  Precision  Recall   F-Measure  MCC      ROC Area  PRC Area  Class
                 0.705    0.101    0.778      0.705    0.740      0.620    0.865     0.787     0
                 0.899    0.295    0.858      0.899    0.878      0.620    0.865     0.912     1
Weighted Avg.    0.834    0.230    0.831      0.834    0.832      0.620    0.865     0.870

=== Confusion Matrix ===

   a   b   <-- classified as
  98  41 |   a = 0
  28 248 |   b = 1

The overall accuracy of the model after cross validation is 83.37%, value which is comparable to that of 83.7% obtained by support vector machine (SVM) with recursive feature elimination (RFE) as published by Li et al. Also the Matthews correlation coefficient (MCC) is quite similar for both models (0.620 vs. 0.645), but the Weka model uses only 9 descriptors instead of 35 of the SVM+RFE model and doesn't include QM properties, reducing dramatically the time required to calculate the parameters. Finally, both models are based on Kier-Hall E-state descriptors but for the random forest model, only 3 descriptors are taken into account instead of 17 of the SVM+RFE model. This is a further advantage in reducing the time for the prediction.

16.2 Prediction of mutagenicy

As the previous example, this is a C-script, which was generated automatically by Tree2C with the aim to classy between mutagen and non-mutagen molecules through a decision model obtained by machine learning. Also in this case, all  attributes were calculated by VEGA ZZ and so no additional code was written manually.

16.2.1 Usage

Since this script shares the same base code of the previous example, you can use it in the same way and, in particular, if a molecule is present in the current workspace, a single classification is performed, otherwise a file requester is shown to select an input database and all molecules of the database are classified saving the result to a CSV file.
Since the training set used in the learning phase to build the model includes molecules in neutral form, also the molecules for which you want to predict the mutagenicity must be in this form.

16.2.2 About the model

To derive the model, the Bursi's dataset (J. Med. Chem., 2005, 48, 312-320) was used as learning set with Weka 3.8 software. All molecules were converted from SMILES to 3D by VEGA ZZ and optimized by MOPAC 2016 (PM7 PRECISE GEO-OK SUPER keywords) keeping them in neutral form. 129 properties/attributes were calculated by both VEGA ZZ and MOPAC 2016. The most significant attributes were selected according to the BestFirst search algorithm (direction = Forward; lookupCacheSize = 1; searchTermination = 5) and the WrapperSubsetEval attribute evaluator (classifier = RandomForest with default settings; doNotCheckCapabilities = False; evaluationMeasure = accuracy, RMSE; folds = 5; seed = 1; threshold = 0.01) as implemented in Weka. In this way, 24 attributes were kept, namely:

As in the previous example, CHARGE_ON_SYSTEM attribute appears in the list because the learning set includes quaternary ammonic molecules that were not neutralized with a counter ion. Some MOPAC attributes were kept during the variable selection procedure and therefore this script requires MOPAC 2016 to perform the classification.
The final model was obtained by Random Forest machine learning algorithm implemented in Weka with default parameters (bagging with 100 iterations and base learner) and performing a 10 fold cross-validation. The results are summarized here, where class 0 and 1 indicate respectively non-mutagen and mutagen substances:

=== Stratified cross-validation ===
=== Summary ===

Correctly Classified Instances        3575               82.4303 %
Incorrectly Classified Instances       762               17.5697 %
Kappa statistic                          0.6442
Mean absolute error                      0.2811
Root mean squared error                  0.3615
Relative absolute error                 56.8678 %
Root relative squared error             72.7173 %
Total Number of Instances             4337

=== Detailed Accuracy By Class ===

                 TP Rate  FP Rate  Precision  Recall   F-Measure  MCC      ROC Area  PRC Area  Class
                 0.798    0.155    0.806      0.798    0.802      0.644    0.896     0.867     0
                 0.845    0.202    0.838      0.845    0.842      0.644    0.896     0.910     1
Weighted Avg.    0.824    0.181    0.824      0.824    0.824      0.644    0.896     0.891

=== Confusion Matrix ===

    a    b   <-- classified as
 1545  391 |    a = 0
  371 2030 |    b = 1

The overall accuracy of Weka model is 82.43%, which is in accordance with the results obtained by Bursi et al. and, in particular, they found a mean accuracy of 82.50%.

17. History

• Release 1.0.0 (03/05/2019)
  First public release.

18. Copyright and disclaimers

All trademarks and software directly or indirectly referred in this document, are copyrighted from legal owners. Tree2C is a freeware program and can be spread through Internet, BBS, CD-ROM and other electronic formats. The Author of this program accepts no responsibility for hardware/software damages resulting from the use of this package. No warranty is made about the software or its performance. Use and copying of this software and the preparation of derivative works based on this software are permitted, so long as the following conditions are met:

• The copyright notice and this entire notice are included intact and prominently carried on all copies and supporting documentation.
   

• No fees or compensation are charged for use, copies, or access to this software. You may charge a nominal distribution fee for the physical act of transferring a copy, but you may not charge for the program itself.
   

• Any work distributed or published that in whole or in part contains or is a derivative of this software or any part thereof is subject to the terms of this agreement. The aggregation of another unrelated program with this software or its derivative on a volume of storage or distribution medium does not bring the other program under the scope of these terms.

Tree2C
is a software developed in 2017-2021
by Alessandro Pedretti
All rights reserved.

Alessandro Pedretti
Dipartimento di Scienze Farmaceutiche
Università degli Studi di Milano
Via Luigi Mangiagalli, 25
I-20133 Milano - Italy
Tel. +39 02 503 19332
Fax. +39 02 503 19359
E-Mail: info@vegazz.net
WWW: http://www.vegazz.net