createExampleSBML.cs

Lengthy example of creating SBML models presented in the SBML specification.

/**
 * @file    createExampleSBML.cpp
 * @brief   Creates example SBML models presented in the SBML specification.
 * @author  Akiya Jouraku
 * @author  Michael Hucka
 * @author  Sarah Keating
 *
 * <!--------------------------------------------------------------------------
 * This sample program is distributed under a different license than the rest
 * of libSBML.  This program uses the open-source MIT license, as follows:
 *
 * Copyright (c) 2013-2018 by the California Institute of Technology
 * (California, USA), the European Bioinformatics Institute (EMBL-EBI, UK)
 * and the University of Heidelberg (Germany), with support from the National
 * Institutes of Health (USA) under grant R01GM070923.  All rights reserved.
 *
 * Permission is hereby granted, free of charge, to any person obtaining a
 * copy of this software and associated documentation files (the "Software"),
 * to deal in the Software without restriction, including without limitation
 * the rights to use, copy, modify, merge, publish, distribute, sublicense,
 * and/or sell copies of the Software, and to permit persons to whom the
 * Software is furnished to do so, subject to the following conditions:
 *
 * The above copyright notice and this permission notice shall be included in
 * all copies or substantial portions of the Software.
 *
 * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
 * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
 * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL
 * THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
 * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING
 * FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER
 * DEALINGS IN THE SOFTWARE.
 *
 * Neither the name of the California Institute of Technology (Caltech), nor
 * of the European Bioinformatics Institute (EMBL-EBI), nor of the University
 * of Heidelberg, nor the names of any contributors, may be used to endorse
 * or promote products derived from this software without specific prior
 * written permission.
 * ------------------------------------------------------------------------ -->
 */

using System;
using System.Collections.Generic;
using System.IO;
using System.Text;
using libsbmlcs;

public class CreateExampleSBML
{

    //
    // The SBML Level and Version of the example SBML models.
    //
    private static int Level = 2;
    private static int Version = 4;


    //===============================================================================
    //
    // Main routine
    //
    //  Creates SBML models represented in "Example models expressed in XML using
    //  SBML" in Section 7 of the SBML Level 2 Version 4 specification(*). 
    //
    //   (*) The specification document is available at the following URL:
    //       http://sbml.org/Documents/Specifications
    //
    //===============================================================================
    //
    public static int Main(string[] args)
    {
        SBMLDocument sbmlDoc = null;
        bool SBMLok = false;

        try
        {
            //-------------------------------------------------
            // 7.1 A Simple example application of SBML
            //-------------------------------------------------

            sbmlDoc = createExampleEnzymaticReaction();
            SBMLok = validateExampleSBML(sbmlDoc);
            if (SBMLok) writeExampleSBML(sbmlDoc, "enzymaticreaction.xml");
            if (!SBMLok) return 1;

            //-------------------------------------------------
            // 7.2 Example involving units
            //-------------------------------------------------

            sbmlDoc = createExampleInvolvingUnits();
            SBMLok = validateExampleSBML(sbmlDoc);
            if (SBMLok) writeExampleSBML(sbmlDoc, "units.xml");
            if (!SBMLok) return 1;

            //-------------------------------------------------
            // 7.8 Example involving function definitions
            //-------------------------------------------------

            sbmlDoc = createExampleInvolvingFunctionDefinitions();
            SBMLok = validateExampleSBML(sbmlDoc);
            if (SBMLok) writeExampleSBML(sbmlDoc, "functiondef.xml");
            if (!SBMLok) return 1;

        }
        catch
        {
            Console.Error.WriteLine("Unexpected exceptional condition encountered.");
            return 1;
        }

        // A 0 return status is the standard Unix/Linux way to say "all ok".
        return 0;

    }


    //===============================================================================
    //
    //
    // Functions for creating the Example SBML documents.
    //
    //
    //===============================================================================


    /**
     *
     * Creates an SBML model represented in "7.1 A Simple example application of SBML"
     * in the SBML Level 2 Version 4 Specification.
     *
     */

    private static SBMLDocument createExampleEnzymaticReaction()
    {
        int level = Level;
        int version = Version;

        //---------------------------------------------------------------------------
        //
        // Creates an SBMLDocument object 
        //
        //---------------------------------------------------------------------------

        SBMLDocument sbmlDoc = new SBMLDocument(level, version);

        //---------------------------------------------------------------------------
        //
        // Creates a Model object inside the SBMLDocument object. 
        //
        //---------------------------------------------------------------------------

        Model model = sbmlDoc.createModel();
        model.setId("EnzymaticReaction");

        //---------------------------------------------------------------------------
        //
        // Creates UnitDefinition objects inside the Model object.
        //
        //---------------------------------------------------------------------------

        // Temporary pointers (reused more than once below).

        UnitDefinition unitdef;
        Unit unit;

        //---------------------------------------------------------------------------  
        // (UnitDefinition1) Creates an UnitDefinition object ("per_second")
        //---------------------------------------------------------------------------

        unitdef = model.createUnitDefinition();
        unitdef.setId("per_second");

        //  Creates an Unit inside the UnitDefinition object 

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_SECOND);
        unit.setExponent(-1);

        //--------------------------------------------------------------------------------
        // (UnitDefinition2) Creates an UnitDefinition object ("litre_per_mole_per_second") 
        //--------------------------------------------------------------------------------

        // Note that we can reuse the pointers 'unitdef' and 'unit' because the
        // actual UnitDefinition object (along with the Unit objects within it)
        // is already attached to the Model object.

        unitdef = model.createUnitDefinition();
        unitdef.setId("litre_per_mole_per_second");

        //  Creates an Unit inside the UnitDefinition object ("litre_per_mole_per_second")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_MOLE);
        unit.setExponent(-1);

        //  Creates an Unit inside the UnitDefinition object ("litre_per_mole_per_second")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_LITRE);
        unit.setExponent(1);

        //  Creates an Unit inside the UnitDefinition object ("litre_per_mole_per_second")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_SECOND);
        unit.setExponent(-1);


        //---------------------------------------------------------------------------
        //
        // Creates a Compartment object inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Compartment comp;
        string compName = "cytosol";

        // Creates a Compartment object ("cytosol")

        comp = model.createCompartment();
        comp.setId(compName);

        // Sets the "size" attribute of the Compartment object.
        //
        // We are not setting the units on the compartment size explicitly, so
        // the units of this Compartment object will be the default SBML units of
        // volume, which are liters.
        //
        comp.setSize(1e-14);


        //---------------------------------------------------------------------------
        //
        // Creates Species objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        // Temporary pointer (reused more than once below).

        Species sp;

        //---------------------------------------------------------------------------
        // (Species1) Creates a Species object ("ES")
        //---------------------------------------------------------------------------

        // Create the Species objects inside the Model object. 

        sp = model.createSpecies();
        sp.setId("ES");
        sp.setName("ES");

        // Sets the "compartment" attribute of the Species object to identify the 
        // compartment in which the Species object is located.

        sp.setCompartment(compName);

        // Sets the "initialAmount" attribute of the Species object.
        //
        //  In SBML, the units of a Species object's initial quantity are
        //  determined by two attributes, "substanceUnits" and
        //  "hasOnlySubstanceUnits", and the "spatialDimensions" attribute
        //  of the Compartment object ("cytosol") in which the species
        //  object is located.  Here, we are using the default values for
        //  "substanceUnits" (which is "mole") and "hasOnlySubstanceUnits"
        //  (which is "false").  The compartment in which the species is
        //  located uses volume units of liters, so the units of these
        //  species (when the species appear in numerical formulas in the
        //  model) will be moles/liters.  
        //
        sp.setInitialAmount(0);

        //---------------------------------------------------------------------------
        // (Species2) Creates a Species object ("P")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setCompartment(compName);
        sp.setId("P");
        sp.setName("P");
        sp.setInitialAmount(0);

        //---------------------------------------------------------------------------
        // (Species3) Creates a Species object ("S")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setCompartment(compName);
        sp.setId("S");
        sp.setName("S");
        sp.setInitialAmount(1e-20);

        //---------------------------------------------------------------------------
        // (Species4) Creates a Species object ("E")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setCompartment(compName);
        sp.setId("E");
        sp.setName("E");
        sp.setInitialAmount(5e-21);


        //---------------------------------------------------------------------------
        //
        // Creates Reaction objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        // Temporary pointers.

        Reaction reaction;
        SpeciesReference spr;
        KineticLaw kl;

        //---------------------------------------------------------------------------
        // (Reaction1) Creates a Reaction object ("veq").
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("veq");

        // (Reactant1) Creates a Reactant object that references Species "E"
        // in the model.  The object will be created within the reaction in the
        // SBML <listOfReactants>.

        spr = reaction.createReactant();
        spr.setSpecies("E");

        // (Reactant2) Creates a Reactant object that references Species "S"
        // in the model.

        spr = reaction.createReactant();
        spr.setSpecies("S");

        //---------------------------------------------------------------------------
        // (Product1) Creates a Product object that references Species "ES" in
        // the model.
        //---------------------------------------------------------------------------

        spr = reaction.createProduct();
        spr.setSpecies("ES");

        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("veq"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        //---------------------------------------------------------------------------
        // Creates an ASTNode object which represents the following math of the
        // KineticLaw.
        //
        //      <math xmlns="http://www.w3.org/1998/Math/MathML">
        //        <apply>
        //          <times/>
        //          <ci> cytosol </ci>
        //          <apply>
        //            <minus/>
        //            <apply>
        //              <times/>
        //              <ci> kon </ci>
        //              <ci> E </ci>
        //              <ci> S </ci>
        //            </apply>
        //            <apply>
        //              <times/>
        //              <ci> koff </ci>
        //              <ci> ES </ci>
        //            </apply>
        //          </apply>
        //        </apply>
        //      </math>
        //
        //---------------------------------------------------------------------------

        //------------------------------------------
        //
        // create nodes representing the variables
        //
        //------------------------------------------

        ASTNode astCytosol = new ASTNode(libsbml.AST_NAME);
        astCytosol.setName("cytosol");

        ASTNode astKon = new ASTNode(libsbml.AST_NAME);
        astKon.setName("kon");

        ASTNode astKoff = new ASTNode(libsbml.AST_NAME);
        astKoff.setName("koff");

        ASTNode astE = new ASTNode(libsbml.AST_NAME);
        astE.setName("E");

        ASTNode astS = new ASTNode(libsbml.AST_NAME);
        astS.setName("S");

        ASTNode astES = new ASTNode(libsbml.AST_NAME);
        astES.setName("ES");


        //--------------------------------------------
        //
        // create node representing
        //            <apply>
        //              <times/>
        //              <ci> koff </ci>
        //              <ci> ES </ci>
        //            </apply>
        //
        //--------------------------------------------

        ASTNode astTimes1 = new ASTNode(libsbml.AST_TIMES);
        astTimes1.addChild(astKoff);
        astTimes1.addChild(astES);

        //--------------------------------------------
        //
        // create node representing
        //            <apply>
        //              <times/>
        //              <ci> kon </ci>
        //              <ci> E </ci>
        //              <ci> S </ci>
        //            </apply>
        //
        //
        // (NOTES)
        //
        //  Since there is a restriction with an ASTNode of "<times/>" operation
        //  such that the ASTNode is a binary class and thus only two operands can
        //  be directly added, the following code in this comment block is invalid
        //  because the code directly adds three <ci> ASTNodes to <times/> ASTNode.
        //
        //    ASTNode *astTimes = new ASTNode(libsbml.AST_TIMES);
        //    astTimes.addChild(astKon);
        //    astTimes.addChild(astE);
        //    astTimes.addChild(astS);
        //
        // The following valid code after this comment block creates the ASTNode
        // as a binary tree.
        //
        // Please see "Converting between ASTs and text strings" described
        // at http://sbml.org/Software/libSBML/docs/cpp-api/class_a_s_t_node.html
        // for the detailed information.
        //
        //--------------------------------------------

        ASTNode astTimes2 = new ASTNode(libsbml.AST_TIMES);
        astTimes2.addChild(astE);
        astTimes2.addChild(astS);

        ASTNode astTimes = new ASTNode(libsbml.AST_TIMES);
        astTimes.addChild(astKon);
        astTimes.addChild(astTimes2);

        //--------------------------------------------
        //
        // create node representing
        //          <apply>
        //            <minus/>
        //            <apply>
        //              <times/>
        //              <ci> kon </ci>
        //              <ci> E </ci>
        //              <ci> S </ci>
        //            </apply>
        //            <apply>
        //              <times/>
        //              <ci> koff </ci>
        //              <ci> ES </ci>
        //            </apply>
        //          </apply>
        //
        //--------------------------------------------

        ASTNode astMinus = new ASTNode(libsbml.AST_MINUS);
        astMinus.addChild(astTimes);
        astMinus.addChild(astTimes1);


        //--------------------------------------------
        //
        // create node representing
        //        <apply>
        //          <times/>
        //          <ci> cytosol </ci>
        //          <apply>
        //            <minus/>
        //            <apply>
        //              <times/>
        //              <ci> kon </ci>
        //              <ci> E </ci>
        //              <ci> S </ci>
        //            </apply>
        //            <apply>
        //              <times/>
        //              <ci> koff </ci>
        //              <ci> ES </ci>
        //            </apply>
        //          </apply>
        //        </apply>
        //
        //--------------------------------------------

        ASTNode astMath = new ASTNode(libsbml.AST_TIMES);
        astMath.addChild(astCytosol);
        astMath.addChild(astMinus);

        //---------------------------------------------
        //
        // set the Math element
        //
        //------------------------------------------------

        kl.setMath(astMath);


        //---------------------------------------------------------------------------
        // Creates local Parameter objects inside the KineticLaw object.
        //---------------------------------------------------------------------------

        // Creates a Parameter ("kon")

        Parameter para = kl.createParameter();
        para.setId("kon");
        para.setValue(1000000);
        para.setUnits("litre_per_mole_per_second");

        // Creates a Parameter ("koff")

        para = kl.createParameter();
        para.setId("koff");
        para.setValue(0.2);
        para.setUnits("per_second");


        //---------------------------------------------------------------------------
        // (Reaction2) Creates a Reaction object ("vcat") .
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("vcat");
        reaction.setReversible(false);

        //---------------------------------------------------------------------------
        // Creates Reactant objects inside the Reaction object ("vcat"). 
        //---------------------------------------------------------------------------

        // (Reactant1) Creates a Reactant object that references Species "ES" in the
        // model.

        spr = reaction.createReactant();
        spr.setSpecies("ES");

        //---------------------------------------------------------------------------
        // Creates a Product object inside the Reaction object ("vcat"). 
        //---------------------------------------------------------------------------

        // (Product1) Creates a Product object that references Species "E" in the model.

        spr = reaction.createProduct();
        spr.setSpecies("E");

        // (Product2) Creates a Product object that references Species "P" in the model.

        spr = reaction.createProduct();
        spr.setSpecies("P");

        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("vcat"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        //---------------------------------------------------------------------------
        // Sets a math (ASTNode object) to the KineticLaw object.
        //---------------------------------------------------------------------------

        // To create mathematical expressions, one would typically construct
        // an ASTNode tree as the above example code which creates a math of another
        // KineticLaw object.  Here, to save some space and illustrate another approach 
        // of doing it, we will write out the formula in MathML form and then use a 
        // libSBML convenience function to create the ASTNode tree for us.  
        // (This is a bit dangerous; it's very easy to make mistakes when writing MathML 
        // by hand, so in a real program, we would not really want to do it this way.)

        string mathXMLString = "<math xmlns=\"http://www.w3.org/1998/Math/MathML\">"
        + "  <apply>"
        + "    <times/>"
        + "    <ci> cytosol </ci>"
        + "    <ci> kcat </ci>"
        + "    <ci> ES </ci>"
        + "  </apply>"
        + "</math>";

        astMath = libsbml.readMathMLFromString(mathXMLString);
        kl.setMath(astMath);


        //---------------------------------------------------------------------------
        // Creates local Parameter objects inside the KineticLaw object.
        //---------------------------------------------------------------------------

        // Creates a Parameter ("kcat")

        para = kl.createParameter();
        para.setId("kcat");
        para.setValue(0.1);
        para.setUnits("per_second");


        // Returns the created SBMLDocument object.
        // The returned object must be explicitly deleted by the caller,
        // otherwise a memory leak will happen.

        return sbmlDoc;

    }


    /**
     *
     * Creates an SBML model represented in "7.2 Example involving units"
     * in the SBML Level 2 Version 4 Specification.
     *
     */

    private static SBMLDocument createExampleInvolvingUnits()
    {
        int level = Level;
        int version = Version;

        //---------------------------------------------------------------------------
        //
        // Creates an SBMLDocument object 
        //
        //---------------------------------------------------------------------------

        SBMLDocument sbmlDoc = new SBMLDocument(level, version);

        // Adds the namespace for XHTML to the SBMLDocument object.  We need this
        // because we will add notes to the model.  (By default, the SBML document
        // created by SBMLDocument only declares the SBML XML namespace.)

        sbmlDoc.getNamespaces().add("http://www.w3.org/1999/xhtml", "xhtml");

        //---------------------------------------------------------------------------
        //
        // Creates a Model object inside the SBMLDocument object. 
        //
        //---------------------------------------------------------------------------

        Model model = sbmlDoc.createModel();
        model.setId("unitsExample");

        //---------------------------------------------------------------------------
        //
        // Creates UnitDefinition objects inside the Model object.
        //
        //---------------------------------------------------------------------------

        // Temporary pointers (reused more than once below).

        UnitDefinition unitdef;
        Unit unit;

        //---------------------------------------------------------------------------  
        // (UnitDefinition1) Creates an UnitDefinition object ("substance").
        //
        // This has the effect of redefining the default unit of subtance for the
        // whole model.
        //---------------------------------------------------------------------------

        unitdef = model.createUnitDefinition();
        unitdef.setId("substance");

        //  Creates an Unit inside the UnitDefinition object 

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_MOLE);
        unit.setScale(-3);

        //--------------------------------------------------------------------------------
        // (UnitDefinition2) Creates an UnitDefinition object ("mmls") 
        //--------------------------------------------------------------------------------

        // Note that we can reuse the pointers 'unitdef' and 'unit' because the
        // actual UnitDefinition object (along with the Unit objects within it)
        // is already attached to the Model object.

        unitdef = model.createUnitDefinition();
        unitdef.setId("mmls");

        //  Creates an Unit inside the UnitDefinition object ("mmls")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_MOLE);
        unit.setScale(-3);

        //  Creates an Unit inside the UnitDefinition object ("mmls")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_LITRE);
        unit.setExponent(-1);

        //  Creates an Unit inside the UnitDefinition object ("mmls")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_SECOND);
        unit.setExponent(-1);

        //--------------------------------------------------------------------------------
        // (UnitDefinition3) Creates an UnitDefinition object ("mml") 
        //--------------------------------------------------------------------------------

        unitdef = model.createUnitDefinition();
        unitdef.setId("mml");

        //  Creates an Unit inside the UnitDefinition object ("mml")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_MOLE);
        unit.setScale(-3);

        //  Creates an Unit inside the UnitDefinition object ("mml")

        unit = unitdef.createUnit();
        unit.setKind(libsbml.UNIT_KIND_LITRE);
        unit.setExponent(-1);


        //---------------------------------------------------------------------------
        //
        // Creates a Compartment object inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Compartment comp;
        string compName = "cell";

        // Creates a Compartment object ("cell")

        comp = model.createCompartment();
        comp.setId(compName);

        // Sets the "size" attribute of the Compartment object.
        //
        //   The units of this Compartment object is the default SBML 
        //   units of volume (litre), and thus we don't have to explicitly invoke 
        //   setUnits("litre") function to set the default units.
        //
        comp.setSize(1);


        //---------------------------------------------------------------------------
        //
        // Creates Species objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        // Temporary pointer (reused more than once below).

        Species sp;

        //---------------------------------------------------------------------------
        // (Species1) Creates a Species object ("x0")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setId("x0");

        // Sets the "compartment" attribute of the Species object to identify the 
        // compartnet in which the Species object located.

        sp.setCompartment(compName);

        // Sets the "initialConcentration" attribute of the Species object.
        //
        //  The units of this Species object is determined by two attributes of this 
        //  Species object ("substanceUnits" and "hasOnlySubstanceUnits") and the
        //  "spatialDimensions" attribute of the Compartment object ("cytosol") in which 
        //  this species object is located.
        //  Since the default values are used for "substanceUnits" (substance (mole)) 
        //  and "hasOnlySubstanceUnits" (false) and the value of "spatialDimension" (3) 
        //  is greater than 0, the units of this Species object is  moles/liters . 
        //
        sp.setInitialConcentration(1);

        //---------------------------------------------------------------------------
        // (Species2) Creates a Species object ("x1")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setId("x1");
        sp.setCompartment(compName);
        sp.setInitialConcentration(1);

        //---------------------------------------------------------------------------
        // (Species3) Creates a Species object ("s1")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setCompartment(compName);
        sp.setId("s1");
        sp.setInitialConcentration(1);

        //---------------------------------------------------------------------------
        // (Species4) Creates a Species object ("s2")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setCompartment(compName);
        sp.setId("s2");
        sp.setInitialConcentration(1);

        //---------------------------------------------------------------------------
        //
        // Creates global Parameter objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Parameter para;

        // Creates a Parameter ("vm")  

        para = model.createParameter();
        para.setId("vm");
        para.setValue(2);
        para.setUnits("mmls");

        // Creates a Parameter ("km")  

        para = model.createParameter();
        para.setId("km");
        para.setValue(2);
        para.setUnits("mml");


        //---------------------------------------------------------------------------
        //
        // Creates Reaction objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        // Temporary pointers.

        Reaction reaction;
        SpeciesReference spr;
        KineticLaw kl;

        //---------------------------------------------------------------------------
        // (Reaction1) Creates a Reaction object ("v1").
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("v1");

        //---------------------------------------------------------------------------
        // Creates Reactant objects inside the Reaction object ("v1"). 
        //---------------------------------------------------------------------------

        // (Reactant1) Creates a Reactant object that references Species "x0"
        // in the model.

        spr = reaction.createReactant();
        spr.setSpecies("x0");

        //---------------------------------------------------------------------------
        // Creates a Product object inside the Reaction object ("v1"). 
        //---------------------------------------------------------------------------

        // Creates a Product object that references Species "s1" in the model. 

        spr = reaction.createProduct();
        spr.setSpecies("s1");

        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("v1"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        // Creates a <notes> element in the KineticLaw object.
        // Here we illustrate how to do it using a literal string.  This requires
        // known the required syntax of XHTML and the requirements for SBML <notes>
        // elements.  Later below, we show how to create notes using objects instead
        // of strings.

        string notesString = "<xhtml:p> ((vm * s1)/(km + s1)) * cell </xhtml:p>";
        kl.setNotes(notesString);

        //---------------------------------------------------------------------------
        // Creates an ASTNode object which represents the following KineticLaw object.
        //
        //  <math xmlns=\"http://www.w3.org/1998/Math/MathML\">
        //   <apply>
        //     <times/>
        //     <apply>
        //       <divide/>
        //       <apply>
        //         <times/>
        //           <ci> vm </ci>
        //           <ci> s1 </ci>
        //       </apply>
        //       <apply>
        //         <plus/>
        //           <ci> km </ci>
        //           <ci> s1 </ci>
        //       </apply>
        //     </apply>
        //     <ci> cell </ci>
        //    </apply>
        //  </math>
        //---------------------------------------------------------------------------

        //
        // In the following code, ASTNode objects, which construct an ASTNode tree 
        // of the above math, are created and added in the order of preorder traversal 
        // of the tree (i.e. the order corresponds to the nested structure of the above 
        // MathML elements), and thus the following code maybe a bit more efficient but 
        // maybe a bit difficult to read.
        //

        ASTNode astMath = new ASTNode(libsbml.AST_TIMES);

        astMath.addChild(new ASTNode(libsbml.AST_DIVIDE));
        ASTNode astDivide = astMath.getLeftChild();

        astDivide.addChild(new ASTNode(libsbml.AST_TIMES));
        ASTNode astTimes = astDivide.getLeftChild();

        astTimes.addChild(new ASTNode(libsbml.AST_NAME));
        astTimes.getLeftChild().setName("vm");

        astTimes.addChild(new ASTNode(libsbml.AST_NAME));
        astTimes.getRightChild().setName("s1");

        astDivide.addChild(new ASTNode(libsbml.AST_PLUS));
        ASTNode astPlus = astDivide.getRightChild();

        astPlus.addChild(new ASTNode(libsbml.AST_NAME));
        astPlus.getLeftChild().setName("km");

        astPlus.addChild(new ASTNode(libsbml.AST_NAME));
        astPlus.getRightChild().setName("s1");


        astMath.addChild(new ASTNode(libsbml.AST_NAME));
        astMath.getRightChild().setName("cell");

        //---------------------------------------------
        //
        // set the Math element
        //
        //------------------------------------------------

        kl.setMath(astMath);

        //---------------------------------------------------------------------------
        // (Reaction2) Creates a Reaction object ("v2").
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("v2");

        //---------------------------------------------------------------------------
        // Creates Reactant objects inside the Reaction object ("v2"). 
        //---------------------------------------------------------------------------

        // (Reactant2) Creates a Reactant object that references Species "s1"
        // in the model.

        spr = reaction.createReactant();
        spr.setSpecies("s1");

        //---------------------------------------------------------------------------
        // Creates a Product object inside the Reaction object ("v2"). 
        //---------------------------------------------------------------------------

        // Creates a Product object that references Species "s2" in the model. 

        spr = reaction.createProduct();
        spr.setSpecies("s2");

        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("v2"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        // Sets a notes (by XMLNode) to the KineticLaw object.
        //
        // The following code is an alternative to using setNotes(const string&).
        // The equivalent code would be like this:
        //   
        //     notesString = "<xhtml:p>((vm * s2)/(km + s2))*cell</xhtml:p>";
        //     kl.setNotes(notesString);

        // Creates an XMLNode of start element (<xhtml:p>) without attributes.

        XMLNode notesXMLNode = new XMLNode(
            new XMLTriple("p", "", "xhtml"),
            new XMLAttributes());

        // Adds a text element to the start element.

        notesXMLNode.addChild(new XMLNode(" ((vm * s2)/(km + s2)) * cell "));

        // Adds it to the kineticLaw object.

        kl.setNotes(notesXMLNode);

        //---------------------------------------------------------------------------
        // Sets a math (ASTNode object) to the KineticLaw object.
        //---------------------------------------------------------------------------

        // To create mathematical expressions, one would typically construct
        // an ASTNode tree as the above example code which creates a math of another
        // KineticLaw object.  Here, to save some space and illustrate another approach 
        // of doing it, we will write out the formula in MathML form and then use a 
        // libSBML convenience function to create the ASTNode tree for us.  
        // (This is a bit dangerous; it's very easy to make mistakes when writing MathML 
        // by hand, so in a real program, we would not really want to do it this way.)

        string mathXMLString = "<math xmlns=\"http://www.w3.org/1998/Math/MathML\">"
        + "  <apply>"
        + "    <times/>"
        + "    <apply>"
        + "      <divide/>"
        + "      <apply>"
        + "        <times/>"
        + "        <ci> vm </ci>"
        + "        <ci> s2 </ci>"
        + "      </apply>"
        + "      <apply>"
        + "        <plus/>"
        + "          <ci> km </ci>"
        + "          <ci> s2 </ci>"
        + "      </apply>"
        + "    </apply>"
        + "    <ci> cell </ci>"
        + "  </apply>"
        + "</math>";

        astMath = libsbml.readMathMLFromString(mathXMLString);
        kl.setMath(astMath);



        //---------------------------------------------------------------------------
        // (Reaction3) Creates a Reaction object ("v3").
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("v3");

        //---------------------------------------------------------------------------
        // Creates Reactant objects inside the Reaction object ("v3"). 
        //---------------------------------------------------------------------------

        // (Reactant2) Creates a Reactant object that references Species "s2"
        // in the model.

        spr = reaction.createReactant();
        spr.setSpecies("s2");

        //---------------------------------------------------------------------------
        // Creates a Product object inside the Reaction object ("v3"). 
        //---------------------------------------------------------------------------

        // Creates a Product object that references Species "x1" in the model. 

        spr = reaction.createProduct();
        spr.setSpecies("x1");


        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("v3"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        // Sets a notes (by string) to the KineticLaw object.

        notesString = "<xhtml:p> ((vm * x1)/(km + x1)) * cell </xhtml:p>";
        kl.setNotes(notesString);

        //---------------------------------------------------------------------------
        // Sets a math (ASTNode object) to the KineticLaw object.
        //---------------------------------------------------------------------------

        mathXMLString = "<math xmlns=\"http://www.w3.org/1998/Math/MathML\">"
        + "  <apply>"
        + "    <times/>"
        + "    <apply>"
        + "      <divide/>"
        + "      <apply>"
        + "        <times/>"
        + "        <ci> vm </ci>"
        + "        <ci> x1 </ci>"
        + "      </apply>"
        + "      <apply>"
        + "        <plus/>"
        + "          <ci> km </ci>"
        + "          <ci> x1 </ci>"
        + "      </apply>"
        + "    </apply>"
        + "    <ci> cell </ci>"
        + "  </apply>"
        + "</math>";

        astMath = libsbml.readMathMLFromString(mathXMLString);
        kl.setMath(astMath);

        // Returns the created SBMLDocument object.
        // The returned object must be explicitly deleted by the caller,
        // otherwise memory leak will happen.

        return sbmlDoc;

    }



    /**
     *
     * Creates an SBML model represented in "7.8 Example involving function definitions"
     * in the SBML Level 2 Version 4 Specification.
     *
     */

    private static SBMLDocument createExampleInvolvingFunctionDefinitions()
    {
        int level = Level;
        int version = Version;

        //---------------------------------------------------------------------------
        //
        // Creates an SBMLDocument object 
        //
        //---------------------------------------------------------------------------

        SBMLDocument sbmlDoc = new SBMLDocument(level, version);

        //---------------------------------------------------------------------------
        //
        // Creates a Model object inside the SBMLDocument object. 
        //
        //---------------------------------------------------------------------------

        Model model = sbmlDoc.createModel();
        model.setId("functionExample");

        //---------------------------------------------------------------------------
        //
        // Creates a FunctionDefinition object inside the Model object. 
        //
        //---------------------------------------------------------------------------

        FunctionDefinition fdef = model.createFunctionDefinition();
        fdef.setId("f");

        // Sets a math (ASTNode object) to the FunctionDefinition object.

        string mathXMLString = "<math xmlns=\"http://www.w3.org/1998/Math/MathML\">"
        + "  <lambda>"
        + "    <bvar>"
        + "      <ci> x </ci>"
        + "    </bvar>"
        + "    <apply>"
        + "      <times/>"
        + "      <ci> x </ci>"
        + "      <cn> 2 </cn>"
        + "    </apply>"
        + "  </lambda>"
        + "</math>";

        ASTNode astMath = libsbml.readMathMLFromString(mathXMLString);
        fdef.setMath(astMath);

        //---------------------------------------------------------------------------
        //
        // Creates a Compartment object inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Compartment comp;
        const string compName = "compartmentOne";

        // Creates a Compartment object ("compartmentOne")

        comp = model.createCompartment();
        comp.setId(compName);

        // Sets the "size" attribute of the Compartment object.
        //
        //   The units of this Compartment object is the default SBML 
        //   units of volume (litre), and thus we don't have to explicitly invoke 
        //   setUnits("litre") function to set the default units.
        //
        comp.setSize(1);


        //---------------------------------------------------------------------------
        //
        // Creates Species objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Species sp;

        //---------------------------------------------------------------------------
        // (Species1) Creates a Species object ("S1")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setId("S1");

        // Sets the "compartment" attribute of the Species object to identify the 
        // compartnet in which the Species object located.

        sp.setCompartment(compName);

        // Sets the "initialConcentration" attribute of the Species object.
        //
        //  The units of this Species object is determined by two attributes of this 
        //  Species object ("substanceUnits" and "hasOnlySubstanceUnits") and the
        //  "spatialDimension" attribute of the Compartment object ("cytosol") in which 
        //  this species object located.
        //  Since the default values are used for "substanceUnits" (substance (mole)) 
        //  and "hasOnlySubstanceUnits" (false) and the value of "spatialDimension" (3) 
        //  is greater than 0, the units of this Species object is  mole/litre . 
        //

        sp.setInitialConcentration(1);

        //---------------------------------------------------------------------------
        // (Species2) Creates a Species object ("S2")
        //---------------------------------------------------------------------------

        sp = model.createSpecies();
        sp.setId("S2");
        sp.setCompartment(compName);
        sp.setInitialConcentration(0);


        //---------------------------------------------------------------------------
        //
        // Creates a global Parameter object inside the Model object. 
        //
        //---------------------------------------------------------------------------

        Parameter para;

        // Creates a Parameter ("t")  

        para = model.createParameter();
        para.setId("t");
        para.setValue(1);
        para.setUnits("second");


        //---------------------------------------------------------------------------
        //
        // Creates Reaction objects inside the Model object. 
        //
        //---------------------------------------------------------------------------

        // Temporary pointers.

        Reaction reaction;
        SpeciesReference spr;
        KineticLaw kl;

        //---------------------------------------------------------------------------
        // (Reaction1) Creates a Reaction object ("reaction_1").
        //---------------------------------------------------------------------------

        reaction = model.createReaction();
        reaction.setId("reaction_1");
        reaction.setReversible(false);

        //---------------------------------------------------------------------------
        // Creates Reactant objects inside the Reaction object ("reaction_1"). 
        //---------------------------------------------------------------------------

        // (Reactant1) Creates a Reactant object that references Species "S1"
        // in the model.

        spr = reaction.createReactant();
        spr.setSpecies("S1");

        //---------------------------------------------------------------------------
        // Creates a Product object inside the Reaction object ("reaction_1"). 
        //---------------------------------------------------------------------------

        // Creates a Product object that references Species "S2" in the model. 

        spr = reaction.createProduct();
        spr.setSpecies("S2");


        //---------------------------------------------------------------------------
        // Creates a KineticLaw object inside the Reaction object ("reaction_1"). 
        //---------------------------------------------------------------------------

        kl = reaction.createKineticLaw();

        //---------------------------------------------------------------------------
        // Sets a math (ASTNode object) to the KineticLaw object.
        //---------------------------------------------------------------------------

        mathXMLString = "<math xmlns=\"http://www.w3.org/1998/Math/MathML\">"
        + "  <apply>"
        + "  <divide/>"
        + "    <apply>"
        + "      <times/>"
        + "      <apply>"
        + "        <ci> f </ci>"
        + "        <ci> S1 </ci>"
        + "      </apply>"
        + "      <ci> compartmentOne </ci>"
        + "    </apply>"
        + "    <ci> t </ci>"
        + "  </apply>"
        + "</math>";

        astMath = libsbml.readMathMLFromString(mathXMLString);
        kl.setMath(astMath);

        // Returns the created SBMLDocument object.
        // The returned object must be explicitly deleted by the caller,
        // otherwise memory leak will happen.

        return sbmlDoc;
    }


    //===============================================================================
    //
    //
    // Helper functions for writing/validating the given SBML documents.
    // 
    //
    //===============================================================================

    /**
     *  
     *  Validates the given SBMLDocument.
     *
     *   This function is based on validateSBML.cpp implemented by
     *   Sarah Keating, Ben Bornstein, and Michael Hucka.
     *
     */

    private static bool validateExampleSBML(SBMLDocument sbmlDoc)
    {
        if (sbmlDoc == null)
        {
            Console.Error.WriteLine("validateExampleSBML: given a null SBML Document");
            return false;
        }

        string consistencyMessages = "";
        string validationMessages = "";
        bool noProblems = true;
        int numCheckFailures = 0;
        int numConsistencyErrors = 0;
        int numConsistencyWarnings = 0;
        int numValidationErrors = 0;
        int numValidationWarnings = 0;

        // LibSBML 3.3 is lenient when generating models from scratch using the
        // API for creating objects.  Once the whole model is done and before it
        // gets written out, it's important to check that the whole model is in
        // fact complete, consistent and valid.

        numCheckFailures = (int)sbmlDoc.checkInternalConsistency();
        if (numCheckFailures > 0)
        {
            noProblems = false;
            for (int i = 0;
            i < numCheckFailures;
            i++)
            {
                SBMLError sbmlErr = sbmlDoc.getError(i);
                if (sbmlErr.isFatal() || sbmlErr.isError())
                {
                    ++numConsistencyErrors;
                }
                else
                {
                    ++numConsistencyWarnings;
                }
            }
            consistencyMessages = sbmlDoc.getErrorLog().toString();
        }

        // If the internal checks fail, it makes little sense to attempt
        // further validation, because the model may be too compromised to
        // be properly interpreted.

        if (numConsistencyErrors > 0)
        {
            consistencyMessages += "Further validation aborted.";
        }
        else
        {
            numCheckFailures = (int)sbmlDoc.checkConsistency();
            if (numCheckFailures > 0)
            {
                noProblems = false;
                for (int i = 0;
                i < numCheckFailures;
                i++)
                {
                    SBMLError sbmlErr = sbmlDoc.getError(i);
                    if (sbmlErr.isFatal() || sbmlErr.isError())
                    {
                        ++numValidationErrors;
                    }
                    else
                    {
                        ++numValidationWarnings;
                    }
                }
                
                validationMessages = sbmlDoc.getErrorLog().toString();
            }
        }

        if (noProblems)
            return true;
        else
        {
            if (numConsistencyErrors > 0)
            {
                Console.WriteLine("ERROR: encountered " + numConsistencyErrors
                + " consistency error" + (numConsistencyErrors == 1 ? "" : "s")
                + " in model '" + sbmlDoc.getModel().getId() + "'.");
            }
            if (numConsistencyWarnings > 0)
            {
                Console.WriteLine("Notice: encountered " + numConsistencyWarnings
                + " consistency warning" + (numConsistencyWarnings == 1 ? "" : "s")
                + " in model '" + sbmlDoc.getModel().getId() + "'.");
            }
            Console.WriteLine();
            Console.WriteLine(consistencyMessages);

            if (numValidationErrors > 0)
            {
                Console.WriteLine("ERROR: encountered " + numValidationErrors
                + " validation error" + (numValidationErrors == 1 ? "" : "s")
                + " in model '" + sbmlDoc.getModel().getId() + "'.");
            }
            if (numValidationWarnings > 0)
            {
                Console.WriteLine("Notice: encountered " + numValidationWarnings
                + " validation warning" + (numValidationWarnings == 1 ? "" : "s")
                + " in model '" + sbmlDoc.getModel().getId() + "'.");
            }
            Console.WriteLine();
            Console.WriteLine(validationMessages);

            return (numConsistencyErrors == 0 && numValidationErrors == 0);
        }
    }


    /**
     *
     * Writes the given SBMLDocument to the given file.
     *
     */
    private static bool writeExampleSBML(SBMLDocument sbmlDoc, string filename)
    {
        int result = libsbml.writeSBML(sbmlDoc, filename);

        if (result == 1)
        {
            Console.WriteLine("Wrote file \"" + filename + "\"");
            return true;
        }
        else
        {
            Console.WriteLine("Failed to write \"" + filename + "\"");
            return false;
        }
    }
}