content: /*
  * Copyright (c) 1997 - 2016
  * Actelion Pharmaceuticals Ltd.
  * Gewerbestrasse 16
  * CH-4123 Allschwil, Switzerland
  *
  * All rights reserved.
  *
  * Redistribution and use in source and binary forms, with or without
  * modification, are permitted provided that the following conditions are met:
  *
  * 1. Redistributions of source code must retain the above copyright notice, this
  *    list of conditions and the following disclaimer.
  * 2. Redistributions in binary form must reproduce the above copyright notice,
  *    this list of conditions and the following disclaimer in the documentation
  *    and/or other materials provided with the distribution.
  * 3. Neither the name of the the copyright holder nor the
  *    names of its contributors may be used to endorse or promote products
  *    derived from this software without specific prior written permission.
  *
  * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" AND
  * ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED
  * WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE
  * DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT OWNER OR CONTRIBUTORS BE LIABLE FOR
  * ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES
  * (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES;
  * LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND
  * ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT
  * (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS
  * SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
  *
  */
  
  package com.actelion.research.chem.prediction;
  
  import com.actelion.research.calc.ThreadMaster;
  import com.actelion.research.chem.Canonizer;
  import com.actelion.research.chem.IDCodeParser;
  import com.actelion.research.chem.SSSearcher;
  import com.actelion.research.chem.SortedStringList;
  import com.actelion.research.chem.StereoMolecule;
  
  import java.io.BufferedReader;
  import java.io.IOException;
  import java.io.InputStreamReader;
  import java.nio.charset.StandardCharsets;
  import java.util.ArrayList;
  
  public class ToxicityPredictor {
      public static final String[] RISK_NAME = { "unknown", "none", "low", "high" };
      public static final int cUnknownRisk = 0;
  	public static final int cNoRisk = 1;
  	public static final int cLowRisk = 2;
  	public static final int cHighRisk = 3;
  
  	public static final int cRiskTypes = 4;
  	public static final int cRiskTypeMutagenic = 0;
  	public static final int cRiskTypeTumorigenic = 1;
  	public static final int cRiskTypeIrritant = 2;
  	public static final int cRiskTypeReproductiveEffective = 3;
  
  	public static final String[] cRiskNameA = {	"mutagenic",
  												"tumorigenic",
  												"irritant",
  												"reproductive effective" };
  	public static final String[] cRiskNameN = {	"Mutagenicity",
  												"Tumorigenicity",
  												"Irritating effects",
  												"Reproductive effects" };
  
  	private static ArrayList<String>[]	sHighRiskFragments;
  	private static ArrayList<String>[]	sLowRiskFragments;
  	private static SortedStringList[]	sRiskMolecules;
      private static boolean				sInitialized;
  
  	@SuppressWarnings("unchecked")
  	public ToxicityPredictor() {
  		synchronized(ToxicityPredictor.class) {
  			if (!sInitialized) {
  				try {
  					sRiskMolecules = new SortedStringList[cRiskTypes];
  					sHighRiskFragments = new ArrayList[cRiskTypes];
  					sLowRiskFragments = new ArrayList[cRiskTypes];
  					sHighRiskFragments[0] = readIDCodeFile("/resources/toxpredictor/m1.txt");
  					sHighRiskFragments[1] = readIDCodeFile("/resources/toxpredictor/t1.txt");
  					sHighRiskFragments[2] = readIDCodeFile("/resources/toxpredictor/i1.txt");
  					sHighRiskFragments[3] = readIDCodeFile("/resources/toxpredictor/r1.txt");
  					sLowRiskFragments[0] = readIDCodeFile("/resources/toxpredictor/m2.txt");
  					sLowRiskFragments[1] = readIDCodeFile("/resources/toxpredictor/t2.txt");
  					sLowRiskFragments[2] = readIDCodeFile("/resources/toxpredictor/i2.txt");
  					sLowRiskFragments[3] = readIDCodeFile("/resources/toxpredictor/r2.txt");
  					sRiskMolecules[0] = readAndSortIDCodeFile("/resources/toxpredictor/m3.txt");
  					sRiskMolecules[1] = readAndSortIDCodeFile("/resources/toxpredictor/t3.txt");
  					sRiskMolecules[2] = readAndSortIDCodeFile("/resources/toxpredictor/i3.txt");
  					sRiskMolecules[3] = readAndSortIDCodeFile("/resources/toxpredictor/r3.txt");
  					sInitialized = true;
  					}
  				catch (Exception e) {
  					System.out.println("Error ToxicityPredictor::initialize() " + e);
  					}
  				}
  			}
  		}
  
  
  	/**
  	 * Before calculating any kind of property, make sure that the molecule's structure is standardized.
  	 * Typically, molecules created by an IDCodeParser are standardized. Molecules generated from a
  	 * SmilesParser or MolfileParser, or just drawn within an editor, should be standardized using the
  	 * MoleculeStandardizer.
  	 * @param mol
  	 * @param riskType one of the four risk types cRiskType...
  	 * @param threadMaster may be null
  	 * @return toxicity risk class estimated from atom type specific increments
  	 */
  	public int assessRisk(StereoMolecule mol, int riskType, ThreadMaster threadMaster) {
  		if (!sInitialized)
  			return cUnknownRisk;
  
  		if (sRiskMolecules[riskType].contains(new Canonizer(mol).getIDCode()))
  			return cHighRisk;
  
  		SSSearcher sss = new SSSearcher(SSSearcher.cMatchAtomCharge);
  		StereoMolecule fragment = new StereoMolecule();
  		for (int i=0; i<sHighRiskFragments[riskType].size(); i++) {
  			if (threadMaster != null && threadMaster.threadMustDie())
  				return cUnknownRisk;
  
  			Thread.yield();
  
  			new IDCodeParser(false).parse(fragment, sHighRiskFragments[riskType].get(i));
  			sss.setMol(fragment, mol);
  			if (sss.isFragmentInMolecule())
  				return cHighRisk;
  			}
  
  		for (int i=0; i<sLowRiskFragments[riskType].size(); i++) {
  			if (threadMaster != null && threadMaster.threadMustDie())
  				return cUnknownRisk;
  
  			Thread.yield();
  
  			new IDCodeParser(false).parse(fragment, sLowRiskFragments[riskType].get(i));
  			sss.setMol(fragment, mol);
  			if (sss.isFragmentInMolecule())
  				return cLowRisk;
  			}
  
  		return cNoRisk;
  		}
  
  
  	public ParameterizedStringList getDetail(StereoMolecule testMolecule, int riskType) {
  		ParameterizedStringList theDetail = new ParameterizedStringList();
  
  		if (!sInitialized) {
  			theDetail.add("Toxicity predictor not properly initialized.",
  								 ParameterizedStringList.cStringTypeText);
  			return theDetail;
  			}
  
  		String idcode = new Canonizer(testMolecule).getIDCode();
  		if (sRiskMolecules[riskType].contains(idcode)) {
  			theDetail.add("This molecule is known to be "+cRiskNameA[riskType]+":",
  								 ParameterizedStringList.cStringTypeText);
  			theDetail.add(idcode, ParameterizedStringList.cStringTypeIDCode);
  			return theDetail;
  			}
  
  		SSSearcher sss = new SSSearcher(SSSearcher.cMatchAtomCharge);
  		boolean found = false;
  		StereoMolecule fragment = new StereoMolecule();
  		for (int i=0; i<sHighRiskFragments[riskType].size(); i++) {
  			new IDCodeParser(false).parse(fragment, sHighRiskFragments[riskType].get(i));
  			sss.setMol(fragment, testMolecule);
  			if (sss.isFragmentInMolecule()) {
  				if (!found)
  					theDetail.add("High-risk fragments indicating "+cRiskNameN[riskType]+":",
  										 ParameterizedStringList.cStringTypeText);
  
  				found = true;
  				theDetail.add(sHighRiskFragments[riskType].get(i), ParameterizedStringList.cStringTypeIDCode);
  				}
  			}
  
  		found = false;
  		for (int i=0; i<sLowRiskFragments[riskType].size(); i++) {
  			new IDCodeParser(false).parse(fragment, sLowRiskFragments[riskType].get(i));
  			sss.setMol(fragment, testMolecule);
  			if (sss.isFragmentInMolecule()) {
  				if (!found)
  					theDetail.add("Medium-risk fragments indicating "+cRiskNameN[riskType]+":",
  										 ParameterizedStringList.cStringTypeText);
  
  				found = true;
  				theDetail.add(sLowRiskFragments[riskType].get(i), ParameterizedStringList.cStringTypeIDCode);
  				}
  			}
  
  		if (theDetail.getSize() == 0)
  			theDetail.add("No indication for "+cRiskNameN[riskType]+" found.",
  								 ParameterizedStringList.cStringTypeText);
  
  		return theDetail;
  		}
  
  
  	private ArrayList<String> readIDCodeFile(String filename) throws Exception {
  		BufferedReader theReader = new BufferedReader(new InputStreamReader(this.getClass().getResourceAsStream(filename), StandardCharsets.UTF_8));
  		ArrayList<String> fragments = new ArrayList<String>();
  		while (true) {
  			try {
  				String idcode = theReader.readLine();
  				if (idcode != null)
  					fragments.add(idcode);
  				else
  					break;
  				}
  			catch (IOException e) {	break; }
  			}
  		theReader.close();
  
  		return fragments;
  		}
  
  
  	private SortedStringList readAndSortIDCodeFile(String filename) throws Exception {
  		BufferedReader theReader = new BufferedReader(new InputStreamReader(this.getClass().getResourceAsStream(filename), StandardCharsets.UTF_8));
  		SortedStringList molecules = new SortedStringList();
  		while (true) {
  			try {
  				String idcode = theReader.readLine();
  				if (idcode != null)
  					molecules.addString(idcode);
  				else
  					break;
  				}
  			catch (IOException e) {	break; }
  			}
  		theReader.close();
  
  		return molecules;
  		}
  	}
  
  
  