toxtree 0.0.1

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/CramerRules.properties

@@ -0,0 +1,11 @@
+explanation=Predicts the toxicological hazard (when administered orally) from the molecular structure. <ul><li>Low (Class I) : Substances with simple chemical structures and for which efficient modes of metabolism exist,suggesting a low order of oral toxicity.<h6>Fifth percentile NOEL (mg/kg bw/day)  3.0 <br>Human exposure threshold  (mg/person/day)  1.8</h6><li>Intermediate (Class II) :Substances which possess structures that are less innocuous than class I substances, but do not contain structural features suggestive of toxicity like those substances in class III. <h6>Fifth percentile NOEL (mg/kg bw/day)  0.91<br> Human exposure threshold  (mg/person/day)  0.54</h6><li>High (Class III).Substances with chemical structures that permit no strong initial presumption of safety or may even suggest significant toxicity or have reactive functional groups.<h6>Fifth percentile NOEL (mg/kg bw/day)  0.15<br> Human exposure threshold  (mg/person/day)  0.09</h6></ul>
+reference1=Cramer G. M., R. A. Ford, R. L. Hall, Estimation of Toxic Hazard - A Decision Tree Approach, J. Cosmet. Toxicol., Vol.16, pp. 255-276, Pergamon Press, 1978
+reference2=I.C. Munro, R.A. Ford, E. Kennepohl, and J.G. Sprenger, Correlation of structural class with No-Observed-Effect Levels: A proposal for establishing a threshold of concern, Food Chem. Toxicol. 34 (1996), pp. 829-867.
+reference3=Patlewicz G, Jeliazkova N, Safford RJ, Worth AP, Aleksiev B. (2008) An evaluation of the implementation of the Cramer classification scheme in the Toxtree software. SAR QSAR Environ Res. ;19(5-6):495-524.
+uri=http://toxtree.sourceforge.net/cramer.html
+vendor=Ideaconsult Ltd.
+vendoruri=http://ideaconsult.net
+priority=1
+endpoint=Oral toxicity
+trainingdata=https://toxtree.svn.sourceforge.net/svnroot/toxtree/trunk/toxtree/toxtree-plugins/toxtree-cramer/src/test/resources/Cramer/CramerRules.csv
+testdata=https://toxtree.svn.sourceforge.net/svnroot/toxtree/trunk/toxtree/toxtree-plugins/toxtree-cramer/src/test/resources/Munro/munro-all.csv

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/CramerTreeResult.java

@@ -0,0 +1,80 @@
+/*
+Copyright Ideaconsult Ltd. (C) 2005-2013 
+
+Contact: www.ideaconsult.net
+
+This program is free software; you can redistribute it and/or
+modify it under the terms of the GNU General Public License
+as published by the Free Software Foundation; either version 2
+of the License, or (at your option) any later version.
+All we ask is that proper credit is given for our work, which includes
+- but is not limited to - adding the above copyright notice to the beginning
+of your source code files, and to any copyright notice that you may distribute
+with programs based on this work.
+
+This program is distributed in the hope that it will be useful,
+but WITHOUT ANY WARRANTY; without even the implied warranty of
+MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+GNU General Public License for more details.
+
+You should have received a copy of the GNU General Public License
+along with this program; if not, write to the Free Software
+Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.
+
+*/
+package toxTree.tree.cramer;
+
+import org.openscience.cdk.interfaces.IAtomContainer;
+
+import toxTree.core.IDecisionRule;
+import toxTree.exceptions.DecisionResultException;
+import toxTree.tree.ProgressStatus;
+import toxTree.tree.TreeResult;
+
+/**
+ * A descendant ot {@link TreeResult}, to be used by {@link toxTree.tree.cramer.CramerRules}.
+ * 
+ * @author Nina Jeliazkova
+ * <b>Modified</b> 2005-9-3
+ */
+public class CramerTreeResult extends TreeResult {
+
+	/**
+	 * Comment for <code>serialVersionUID</code>
+	 */
+	private static final long serialVersionUID = -7883635712321700678L;
+
+	/**
+	 * 
+	 */
+	public CramerTreeResult() {
+		super();
+	}
+	/* (non-Javadoc)
+	 * @see toxTree.tree.TreeResult#addRuleResult(int, boolean)
+	 */
+	@Override
+	public void addRuleResult(IDecisionRule rule, boolean value, IAtomContainer molecule)
+			throws DecisionResultException {
+		super.addRuleResult(rule, value,molecule);
+		if (rule.getNum() > 33) 
+			setSilent(true);
+	}
+    @Override
+	public void assignResult(IAtomContainer mol) throws DecisionResultException {
+    	if (mol ==null) return;
+    	if (getCategory()!=null)
+        mol.setProperty(
+        		getResultPropertyNames()[0],
+                getCategory().toString());
+        mol.setProperty(
+                getClass().getName(),
+                explain(false).toString());
+        firePropertyChangeEvent(ProgressStatus._pRuleResult, null, status);
+    }
+    @Override
+    public String[] getResultPropertyNames() {
+    	return new String[] {"Cramer rules"};
+    }
+    
+}

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/Rule32.java

@@ -0,0 +1,136 @@
+/*
+Copyright Ideaconsult Ltd. (C) 2005-2007 
+
+Contact: nina@acad.bg
+
+This program is free software; you can redistribute it and/or
+modify it under the terms of the GNU General Public License
+as published by the Free Software Foundation; either version 2
+of the License, or (at your option) any later version.
+All we ask is that proper credit is given for our work, which includes
+- but is not limited to - adding the above copyright notice to the beginning
+of your source code files, and to any copyright notice that you may distribute
+with programs based on this work.
+
+This program is distributed in the hope that it will be useful,
+but WITHOUT ANY WARRANTY; without even the implied warranty of
+MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+GNU General Public License for more details.
+
+You should have received a copy of the GNU General Public License
+along with this program; if not, write to the Free Software
+Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.
+
+*/
+package toxTree.tree.cramer;
+
+import org.openscience.cdk.CDKConstants;
+import org.openscience.cdk.interfaces.IAtomContainer;
+import org.openscience.cdk.interfaces.IRing;
+import org.openscience.cdk.interfaces.IRingSet;
+import org.openscience.cdk.isomorphism.matchers.QueryAtomContainer;
+
+import toxTree.exceptions.DecisionMethodException;
+import toxTree.query.FunctionalGroups;
+import toxTree.query.MolFlags;
+import toxTree.tree.rules.RuleOnlyAllowedSubstructures;
+
+/**
+ * 
+ * Rule 32 of the Cramer scheme (see {@link toxTree.tree.cramer.CramerRules})
+ * @author Nina Jeliazkova
+ * <b>Modified</b> 2005-10-18
+ */
+public class Rule32 extends RuleOnlyAllowedSubstructures {
+	QueryAtomContainer polyoxyethylene5;
+	/**
+	 * 
+	 */
+	private static final long serialVersionUID = 2629244201826413885L;
+
+	public Rule32() {
+		super();
+		id = "32";
+		title = "Contains only the functional groups listed in Q30 or Q31 and those listed below.";
+		explanation.append("<html>");
+		explanation.append("Does the substance contain only the <i>functional groups</i> (E) listed in Q30, or their derivatives listed in Q31, but with any or all of the following:<UL>");
+		explanation.append("<LI>(a)a single fused non-aromatic carbocyclic ring");
+		explanation.append("<LI>(b)<i>aliphatic</i> (A) substituent chains longer than 5 carbon atoms, or");
+		explanation.append("<LI>(c)a polyoxyethylene [(-OCH2CH2-)x, with x <= 4] chain either on the aromatic ring or on an aliphatic side chain?");
+		explanation.append("</UL>");
+		explanation.append("<P>Part (a) is intended to allow simple derivatives of tetralin into class II while putting polyciclic compounds such as steroids ultimately into class III except those that may be normal food components.");
+		
+		explanation.append("<p>Part (b) allows compounds with permitted functional groups but longer side chains into class II instead of sending them eventually into class III.");
+		explanation.append("<p>Part (c) puts short-chain polyoxyethylene derivatives of aryl compounds into class II rather than class III.");
+		explanation.append("</html>");
+		examples[0] = "CSC1=CC=CC=C1";
+		examples[1] = "CC(C)CCC(=O)C1=CC=CC=C1";
+		
+		addSubstructure(FunctionalGroups.hydroxy_ring());
+		addSubstructure(FunctionalGroups.methoxy_ring());
+		addSubstructure(FunctionalGroups.alcohol(false));
+		addSubstructure(FunctionalGroups.ketone());
+		addSubstructure(FunctionalGroups.aldehyde());
+		addSubstructure(FunctionalGroups.carboxylicAcid());
+		addSubstructure(FunctionalGroups.ester());
+		addSubstructure(FunctionalGroups.acyclic_acetal());
+		addSubstructure(FunctionalGroups.polyoxyethylene(1));
+		
+		polyoxyethylene5 = FunctionalGroups.polyoxyethylene(5); 
+		
+		editable = false;
+
+	}
+	@Override
+	public boolean isImplemented() {
+		return true;
+	}
+	/**
+	 * 
+	 * @param mol
+	 * @param rings
+	 * @return
+	 */
+	protected boolean singleFusedNonAromaticCarbocyclicRing(IAtomContainer  mol, IRingSet rings) {
+		final String c = "C";
+		if (FunctionalGroups.singleFusedRing(mol,rings)) {
+			for (int i = 0; i < rings.getAtomContainerCount(); i++) {
+				IRing ring = (IRing) rings.getAtomContainer(i);
+				if (ring.getFlag(CDKConstants.ISAROMATIC)) {
+					logger.finer("Aromatic ring found");
+					return false;
+				}
+				for (int j = 0; j < ring.getAtomCount(); j++) 
+					if (!ring.getAtom(j).getSymbol().equals(c)) {
+						logger.finer("Heteroring found\t"+ring.getAtom(j).getSymbol());								
+						return false;
+					}
+			}
+			//
+			return true;
+		} else return false;
+	}
+	
+	/**
+	 * @see toxTree.core.IDecisionRule#verifyRule(IAtomContainer)
+	 */
+	@Override
+	public boolean verifyRule(IAtomContainer mol) throws DecisionMethodException {
+		logger.finer(toString());
+		if (super.verifyRule(mol)) {
+			logger.finer(toString());
+		    MolFlags mf = (MolFlags) mol.getProperty(MolFlags.MOLFLAGS);
+		    if (mf == null) throw new DecisionMethodException(ERR_STRUCTURENOTPREPROCESSED);
+		    IRingSet rings = mf.getRingset();		
+			if (singleFusedNonAromaticCarbocyclicRing(mol, rings)) {
+				logger.finer("Single Fused NonAromatic CarbocyclicRing\tYES");
+				return true;
+			}			
+			if (FunctionalGroups.hasGroup(mol,polyoxyethylene5)) {
+				logger.finer("Polyoxyethylene (-OCH2CH2-)x, x>4");
+				return false;
+			} else return true;
+		} else return false;
+	}
+
+}

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/Rule3FuncGroups.java

@@ -0,0 +1,95 @@
+/*
+Copyright Ideaconsult Ltd. (C) 2005-2007 
+
+Contact: nina@acad.bg
+
+This program is free software; you can redistribute it and/or
+modify it under the terms of the GNU General Public License
+as published by the Free Software Foundation; either version 2
+of the License, or (at your option) any later version.
+All we ask is that proper credit is given for our work, which includes
+- but is not limited to - adding the above copyright notice to the beginning
+of your source code files, and to any copyright notice that you may distribute
+with programs based on this work.
+
+This program is distributed in the hope that it will be useful,
+but WITHOUT ANY WARRANTY; without even the implied warranty of
+MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+GNU General Public License for more details.
+
+You should have received a copy of the GNU General Public License
+along with this program; if not, write to the Free Software
+Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.
+
+*/
+package toxTree.tree.cramer;
+
+import org.openscience.cdk.interfaces.IAtomContainer;
+
+import toxTree.exceptions.DecisionMethodException;
+import toxTree.query.FunctionalGroups;
+import toxTree.tree.AbstractRuleHilightHits;
+
+/**
+ * Rule 21 of the Cramer scheme (see {@link toxTree.tree.cramer.CramerRules})
+ * @author Nina Jeliazkova <br>
+ * @version 0.1, 2005-5-2
+ */
+public class Rule3FuncGroups extends AbstractRuleHilightHits {
+
+	/**
+     * Comment for <code>serialVersionUID</code>
+     */
+    private static final long serialVersionUID = 300792171250153478L;
+
+    /**
+	 * Constructor
+	 * 
+	 */
+	public Rule3FuncGroups() {
+		super();
+		id = "21";
+		title = "3 or more different functional groups";
+		explanation.append("<html>Does the structure contain >= 3 different types of functional groups (exclude methoxy and consider acids and esters as one functional type)?<p>");
+		explanation.append("<I>Aliphatic</i> (A) compounds containing three or more different functional groups (excluding methoxy) are too complex to permit satisfactory prediction of toxicity. they should go therefore, into class III.");
+		explanation.append("however, we do not wish to put into class III polyesters and similar substances, so these and the methoxy compounds get passed along to Q18.</html>");
+		examples[0] = "CCCCOC(=O)CC(CC(=O)OCCCC)OC(C)=O";
+		examples[1] = "[H]C(N)(CCSCC)C(O)=O";
+		editable = false;
+	}
+	/* (non-Javadoc)
+	 * @see toxTree.tree.AbstractRule#isImplemented()
+	 */
+	@Override
+	public boolean isImplemented() {
+		return true;
+	}
+	/**
+	 * {@link toxTree.core.IDecisionRule#verifyRule(IAtomContainer)}
+	 */
+	public boolean verifyRule(IAtomContainer  mol) throws DecisionMethodException {
+		return verifyRule(mol,null);
+	}
+	
+	@Override
+	public boolean verifyRule(IAtomContainer mol, IAtomContainer selected)
+			throws DecisionMethodException {
+		logger.finer(toString());
+		try {
+			boolean ok = FunctionalGroups.hasManyDifferentFunctionalGroups(mol,3);
+			if (selected != null) {
+				for (int i=0; i < mol.getAtomCount(); i++)
+					if (mol.getAtom(i).getProperty(FunctionalGroups.ALLOCATED)!=null)
+						selected.addAtom(mol.getAtom(i));
+				for (int i=0; i < mol.getBondCount(); i++)
+					if (mol.getBond(i).getProperty(FunctionalGroups.ALLOCATED)!=null)
+						selected.addBond(mol.getBond(i));				
+			}	
+			
+			return ok;
+		} catch (Exception x) {
+			throw new DecisionMethodException(x);
+		}
+	}
+
+}

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/Rule3MemberedHeterocycle.java

@@ -0,0 +1,84 @@
+/*
+Copyright Ideaconsult Ltd. (C) 2005-2007 
+
+Contact: nina@acad.bg
+
+This program is free software; you can redistribute it and/or
+modify it under the terms of the GNU General Public License
+as published by the Free Software Foundation; either version 2
+of the License, or (at your option) any later version.
+All we ask is that proper credit is given for our work, which includes
+- but is not limited to - adding the above copyright notice to the beginning
+of your source code files, and to any copyright notice that you may distribute
+with programs based on this work.
+
+This program is distributed in the hope that it will be useful,
+but WITHOUT ANY WARRANTY; without even the implied warranty of
+MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+GNU General Public License for more details.
+
+You should have received a copy of the GNU General Public License
+along with this program; if not, write to the Free Software
+Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.
+
+*/
+package toxTree.tree.cramer;
+
+import net.idea.modbcum.i.processors.IProcessor;
+
+import org.openscience.cdk.interfaces.IAtomContainer;
+import org.openscience.cdk.renderer.selection.IChemObjectSelection;
+
+import toxTree.exceptions.DecisionMethodException;
+import toxTree.query.MolFlags;
+import toxTree.tree.AbstractRule;
+import toxTree.tree.rules.smarts.RuleSMARTSSubstructureAmbit;
+
+/**
+ * 3-membered heterocycle. Rule 10 of the Cramer scheme (see {@link toxTree.tree.cramer.CramerRules})
+ * @author Nina Jeliazkova <br>
+ * @version 0.1, 2005-5-2
+ */
+public class Rule3MemberedHeterocycle extends AbstractRule {
+
+	/**
+     * Comment for <code>serialVersionUID</code>
+     */
+    private static final long serialVersionUID = 7684875450263940055L;
+    /**
+	 * Constructor
+	 * 
+	 */
+	public Rule3MemberedHeterocycle() {
+		super();
+		id = "10";
+		title = "3-membered heterocycle";
+		explanation.append("<html>Is it a 3-membered heterocycle<p>");
+		explanation.append("This places such substances as epoxides and ethylenamine in class III</html>");
+		examples[0] = "C1CC1C2=COC=C2";
+		examples[1] = "COC(=O)C1OC1(C)C2=CC=CC=C2";
+		editable = false;
+	}
+	/**
+	 * {@link toxTree.core.IDecisionRule#verifyRule(IAtomContainer)}
+	 */
+	public boolean verifyRule(IAtomContainer  mol) throws DecisionMethodException {
+	    //should be set via MolAnalyser
+		logger.finer(toString());
+	    MolFlags mf = (MolFlags) mol.getProperty(MolFlags.MOLFLAGS);
+	    return  mf.isHeterocyclic3();
+	}
+	/* (non-Javadoc)
+     * @see toxTree.tree.AbstractRule#isImplemented()
+     */
+    @Override
+	public boolean isImplemented() {
+        return true;
+    }	
+    @Override
+    public IProcessor<IAtomContainer, IChemObjectSelection> getSelector() {
+    	RuleSMARTSSubstructureAmbit rule = new RuleSMARTSSubstructureAmbit();
+    	try { rule.addSubstructure("C1[!#6]C1"); } catch (Exception x) {x.printStackTrace();};
+    	return rule.getSelector();
+    }    
+}

data/Toxtree-v2.6.13/src/toxTree/tree/cramer/RuleAcyclicAcetalEsterOfQ30.java

@@ -0,0 +1,102 @@
+/*
+Copyright Ideaconsult Ltd. (C) 2005-2007 
+
+Contact: nina@acad.bg
+
+This program is free software; you can redistribute it and/or
+modify it under the terms of the GNU General Public License
+as published by the Free Software Foundation; either version 2
+of the License, or (at your option) any later version.
+All we ask is that proper credit is given for our work, which includes
+- but is not limited to - adding the above copyright notice to the beginning
+of your source code files, and to any copyright notice that you may distribute
+with programs based on this work.
+
+This program is distributed in the hope that it will be useful,
+but WITHOUT ANY WARRANTY; without even the implied warranty of
+MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
+GNU General Public License for more details.
+
+You should have received a copy of the GNU General Public License
+along with this program; if not, write to the Free Software
+Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.
+
+*/
+package toxTree.tree.cramer;
+
+import org.openscience.cdk.interfaces.IAtomContainer;
+import org.openscience.cdk.interfaces.IAtomContainerSet;
+import org.openscience.cdk.isomorphism.matchers.QueryAtomContainer;
+
+import toxTree.exceptions.DecisionMethodException;
+import toxTree.exceptions.ReactionException;
+import toxTree.query.FunctionalGroups;
+import toxTree.query.MolFlags;
+import toxTree.query.SimpleReactions;
+
+/**
+ * Rule 31 of the Cramer scheme (see {@link toxTree.tree.cramer.CramerRules})
+ * @author Nina Jeliazkova <br>
+ * @version 0.1, 2005-5-3
+ */
+public class RuleAcyclicAcetalEsterOfQ30 extends RuleRingComplexSubstituents30 {
+	protected QueryAtomContainer acetal;
+	protected QueryAtomContainer ester;
+	/**
+     * Comment for <code>serialVersionUID</code>
+     */
+    private static final long serialVersionUID = 5048900098470975756L;;
+    /**
+	 * Constructor
+	 * 
+	 */
+	public RuleAcyclicAcetalEsterOfQ30() {
+		super();
+		//this checks only for acyclic acetal and ester, 
+		//assumes that molecule already had successfully passed through Q30 
+		acetal = FunctionalGroups.acyclic_acetal();
+		ester = FunctionalGroups.ester();
+		id = "31";
+		title = "Is the substance an acyclic acetal or ester of substances defined in Q30?";
+		explanation = new StringBuffer();
+		explanation.append("<html>");
+		explanation.append("Is the substance an acyclic acetal, -ketal or -ester of any of the above substances (see Q30)?");
+		explanation.append("(If YES, assume hydrolysis and treat the non-aromatic residues by Q19 and the aromatic residue by Q18.)<p>");
+		explanation.append("This question is simply designed to see whether the substance would fit within the definition of Q30 if it were not an acetal, a ketal or an ester.");
+		explanation.append("In other words, would the substance carry only the groups listed in Q30.");
+		explanation.append("</html>");
+		examples[0] = "NC1=CC=CC=C1";
+		examples[1] = "COC(OC)C1=CC=CC=C1";
+		editable = false;
+	}
+	@Override
+	public boolean verifyRule(IAtomContainer  mol) throws DecisionMethodException {
+		return verifyRule(mol, null);
+	}
+	/* (non-Javadoc)
+	 * @see toxTree.tree.rules.RuleAnySubstructure#verifyRule(org.openscience.cdk.Molecule)
+	 */
+	@Override
+	public boolean verifyRule(IAtomContainer mol, IAtomContainer selected)
+			throws DecisionMethodException {
+		if (!super.verifyRule(mol,selected)) {
+			if (FunctionalGroups.hasGroup(mol,acetal) || FunctionalGroups.hasGroup(mol,ester)) { 
+			
+				SimpleReactions sr = new SimpleReactions();
+				try {
+					IAtomContainerSet residues = sr.isReadilyHydrolised(mol);
+					if (residues != null) {
+					    MolFlags mf = (MolFlags) mol.getProperty(MolFlags.MOLFLAGS);
+					    if (mf == null) throw new DecisionMethodException("Structure should be preprocessed!");
+					    mf.setHydrolysisProducts(residues);
+					    mf.setResidues(residues);
+					}
+					return true;
+				} catch (ReactionException x) {
+					throw new DecisionMethodException(x);
+				}
+			} else return false;	
+			//hydrolysis
+		} else return false;
+	}
+}