int main() {
  TreeTemplate<Node>* tree = TreeTemplateTools::parenthesisToTree("(((A:0.01, B:0.01):0.02,C:0.03):0.01,D:0.04);");
  vector<string> seqNames = tree->getLeavesNames();
  vector<int> ids = tree->getNodesId();
  //-------------

  const NucleicAlphabet* alphabet = &AlphabetTools::DNA_ALPHABET;
  SubstitutionModel* model = new T92(alphabet, 3.);
  DiscreteDistribution* rdist = new GammaDiscreteDistribution(4, 1.0);
  rdist->aliasParameters("alpha", "beta");

  VectorSiteContainer sites(alphabet);
  sites.addSequence(BasicSequence("A", "AAATGGCTGTGCACGTC", alphabet));
  sites.addSequence(BasicSequence("B", "AACTGGATCTGCATGTC", alphabet));
  sites.addSequence(BasicSequence("C", "ATCTGGACGTGCACGTG", alphabet));
  sites.addSequence(BasicSequence("D", "CAACGGGAGTGCGCCTA", alphabet));

  try {
    fitModelH(model, rdist, *tree, sites, 93.017264552603336369, 71.265543199977557265);
  } catch (Exception& ex) {
    cerr << ex.what() << endl;
    return 1;
  }
  try {
    fitModelHClock(model, rdist, *tree, sites, 92.27912072473920090943, 71.26554020984087856050);
  } catch (Exception& ex) {
    cerr << ex.what() << endl;
    return 1;
  }

  //-------------
  delete tree;
  delete model;
  delete rdist;

  return 0;
}
Exemplo n.º 2
0
int main() {
  TreeTemplate<Node>* tree = TreeTemplateTools::parenthesisToTree("((A:0.01, B:0.02):0.03,C:0.01,D:0.1);");
  vector<string> seqNames= tree->getLeavesNames();
  vector<int> ids = tree->getNodesId();
  //-------------

  NucleicAlphabet* alphabet = new DNA();
  SubstitutionModel* model = new T92(alphabet, 3.);
  FrequenciesSet* rootFreqs = new GCFrequenciesSet(alphabet);
  std::vector<std::string> globalParameterNames;
  globalParameterNames.push_back("T92.kappa");
  map<string, string> alias;

  SubstitutionModelSet* modelSet = SubstitutionModelSetTools::createNonHomogeneousModelSet(model, rootFreqs, tree, alias, globalParameterNames);
  DiscreteDistribution* rdist = new ConstantRateDistribution();
  vector<double> thetas;
  for (unsigned int i = 0; i < modelSet->getNumberOfModels(); ++i) {
    double theta = RandomTools::giveRandomNumberBetweenZeroAndEntry(0.99) + 0.005;
    cout << "Theta" << i << " set to " << theta << endl; 
    modelSet->setParameterValue("T92.theta_" + TextTools::toString(i + 1), theta);
    thetas.push_back(theta);
  }
  NonHomogeneousSequenceSimulator simulator(modelSet, rdist, tree);

  unsigned int n = 100000;
  OutputStream* profiler  = new StlOutputStream(new ofstream("profile.txt", ios::out));
  OutputStream* messenger = new StlOutputStream(new ofstream("messages.txt", ios::out));

  //Check fast simulation first:
 
  cout << "Fast check:" << endl;
 
  //Generate data set:
  VectorSiteContainer sites(seqNames, alphabet);
  for (unsigned int i = 0; i < n; ++i) {
    auto_ptr<Site> site(simulator.simulateSite());
    site->setPosition(static_cast<int>(i));
    sites.addSite(*site, false);
  }

  //Now fit model:
  SubstitutionModelSet* modelSet2 = modelSet->clone();
  RNonHomogeneousTreeLikelihood tl(*tree, sites, modelSet2, rdist);
  tl.initialize();

  OptimizationTools::optimizeNumericalParameters2(
      &tl, tl.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

  //Now compare estimated values to real ones:
  for (size_t i = 0; i < thetas.size(); ++i) {
    cout << thetas[i] << "\t" << modelSet2->getModel(i)->getParameter("theta").getValue() << endl;
    double diff = abs(thetas[i] - modelSet2->getModel(i)->getParameter("theta").getValue());
    if (diff > 0.1)
      return 1;
  }
  delete modelSet2;

  //Now try detailed simulations:

  cout << "Detailed check:" << endl;
  
  //Generate data set:
  VectorSiteContainer sites2(seqNames, alphabet);
  for (unsigned int i = 0; i < n; ++i) {
    RASiteSimulationResult* result = simulator.dSimulateSite();
    auto_ptr<Site> site(result->getSite(*simulator.getSubstitutionModelSet()->getModel(0)));
    site->setPosition(static_cast<int>(i));
    sites2.addSite(*site, false);
    delete result;
  }

  //Now fit model:
  SubstitutionModelSet* modelSet3 = modelSet->clone();
  RNonHomogeneousTreeLikelihood tl2(*tree, sites2, modelSet3, rdist);
  tl2.initialize();

  OptimizationTools::optimizeNumericalParameters2(
      &tl2, tl2.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

  //Now compare estimated values to real ones:
  for (size_t i = 0; i < thetas.size(); ++i) {
    cout << thetas[i] << "\t" << modelSet3->getModel(i)->getParameter("theta").getValue() << endl;
    double diff = abs(thetas[i] - modelSet3->getModel(i)->getParameter("theta").getValue());
    if (diff > 0.1)
      return 1;
  }
  delete modelSet3;

  //-------------
  delete tree;
  delete alphabet;
  delete modelSet;
  delete rdist;

  return 0;
}
Exemplo n.º 3
0
int main() {
  TreeTemplate<Node>* tree = TreeTemplateTools::parenthesisToTree("((A:0.001, B:0.002):0.008,C:0.01,D:0.1);");
  vector<int> ids = tree->getNodesId();
  ids.pop_back(); //Ignore root

  //-------------

  CodonAlphabet* alphabet = new CodonAlphabet(&AlphabetTools::DNA_ALPHABET);
  GeneticCode* gc = new StandardGeneticCode(&AlphabetTools::DNA_ALPHABET);
  CodonSubstitutionModel* model = new YN98(gc, CodonFrequenciesSet::getFrequenciesSetForCodons(CodonFrequenciesSet::F0, gc));
  //SubstitutionModel* model = new CodonRateSubstitutionModel(
  //      gc,
  //      new JCnuc(dynamic_cast<CodonAlphabet*>(alphabet)->getNucleicAlphabet()));
  cout << model->getNumberOfStates() << endl;
  MatrixTools::printForR(model->getGenerator(), "g");
  DiscreteDistribution* rdist = new ConstantDistribution(1.0);
  HomogeneousSequenceSimulator simulator(model, rdist, tree);
  TotalSubstitutionRegister* totReg = new TotalSubstitutionRegister(model);
  DnDsSubstitutionRegister* dndsReg = new DnDsSubstitutionRegister(model);

  unsigned int n = 20000;
  vector< vector<double> > realMap(n);
  vector< vector< vector<double> > > realMapTotal(n);
  vector< vector< vector<double> > > realMapDnDs(n);
  VectorSiteContainer sites(tree->getLeavesNames(), alphabet);
  for (unsigned int i = 0; i < n; ++i) {
    ApplicationTools::displayGauge(i, n-1, '=');
    RASiteSimulationResult* result = simulator.dSimulateSite();
    realMap[i].resize(ids.size());
    realMapTotal[i].resize(ids.size());
    realMapDnDs[i].resize(ids.size());
    for (size_t j = 0; j < ids.size(); ++j) {
      realMap[i][j] = static_cast<double>(result->getSubstitutionCount(ids[j]));
      realMapTotal[i][j].resize(totReg->getNumberOfSubstitutionTypes());
      realMapDnDs[i][j].resize(dndsReg->getNumberOfSubstitutionTypes());
      result->getSubstitutionCount(ids[j], *totReg, realMapTotal[i][j]);
      result->getSubstitutionCount(ids[j], *dndsReg, realMapDnDs[i][j]);
      if (realMapTotal[i][j][0] != realMap[i][j]) {
        cerr << "Error, total substitution register provides wrong result." << endl;
        return 1;
      }
      //if (abs(VectorTools::sum(realMapDetailed[i][j]) - realMap[i][j]) > 0.000001) {
      //  cerr << "Error, detailed substitution register provides wrong result." << endl;
      //  return 1;
      //}
    }
    auto_ptr<Site> site(result->getSite(*model));
    site->setPosition(static_cast<int>(i));
    sites.addSite(*site, false);
    delete result;
  }
  ApplicationTools::displayTaskDone();
  
  //-------------
  //Now build the substitution vectors with the true model:
  //Fasta fasta;
  //fasta.write("Simulations.fasta", sites);
  DRHomogeneousTreeLikelihood drhtl(*tree, sites, model, rdist);
  drhtl.initialize();
  cout << drhtl.getValue() << endl;
 
  SubstitutionCount* sCountAna = new LaplaceSubstitutionCount(model, 10);
  Matrix<double>* m = sCountAna->getAllNumbersOfSubstitutions(0.001,1);
  cout << "Analytical total count:" << endl;
  MatrixTools::print(*m);
  delete m;
  ProbabilisticSubstitutionMapping* probMapAna = 
    SubstitutionMappingTools::computeSubstitutionVectors(drhtl, ids, *sCountAna);

  SubstitutionCount* sCountTot = new NaiveSubstitutionCount(model, totReg);
  m = sCountTot->getAllNumbersOfSubstitutions(0.001,1);
  cout << "Simple total count:" << endl;
  MatrixTools::print(*m);
  delete m;
  ProbabilisticSubstitutionMapping* probMapTot = 
    SubstitutionMappingTools::computeSubstitutionVectors(drhtl, ids, *sCountTot);

  SubstitutionCount* sCountDnDs = new NaiveSubstitutionCount(model, dndsReg);
  m = sCountDnDs->getAllNumbersOfSubstitutions(0.001,1);
  cout << "Detailed count, type 1:" << endl;
  MatrixTools::print(*m);
  delete m;
  ProbabilisticSubstitutionMapping* probMapDnDs = 
    SubstitutionMappingTools::computeSubstitutionVectors(drhtl, ids, *sCountDnDs);

  SubstitutionCount* sCountUniTot = new UniformizationSubstitutionCount(model, totReg);
  m = sCountUniTot->getAllNumbersOfSubstitutions(0.001,1);
  cout << "Total count, uniformization method:" << endl;
  MatrixTools::print(*m);
  delete m;
  ProbabilisticSubstitutionMapping* probMapUniTot = 
    SubstitutionMappingTools::computeSubstitutionVectors(drhtl, ids, *sCountUniTot);

  SubstitutionCount* sCountUniDnDs = new UniformizationSubstitutionCount(model, dndsReg);
  m = sCountUniDnDs->getAllNumbersOfSubstitutions(0.001,2);
  cout << "Detailed count, uniformization method, type 2:" << endl;
  MatrixTools::print(*m);
  delete m;
  ProbabilisticSubstitutionMapping* probMapUniDnDs = 
    SubstitutionMappingTools::computeSubstitutionVectors(drhtl, ids, *sCountUniDnDs);

  //Check per branch:
  
  /*
  //1. Total:
  for (unsigned int j = 0; j < ids.size(); ++j) {
    double totalReal = 0;
    double totalObs1 = 0;
    double totalObs2 = 0;
    double totalObs3 = 0;
    double totalObs4 = 0;
    double totalObs5 = 0;
    for (unsigned int i = 0; i < n; ++i) {
      totalReal += realMap[i][j];
      totalObs1 += probMapAna->getNumberOfSubstitutions(ids[j], i, 0);
      totalObs2 += probMapTot->getNumberOfSubstitutions(ids[j], i, 0);
      //totalObs3 += VectorTools::sum(probMapDet->getNumberOfSubstitutions(ids[j], i));
      totalObs4 += probMapDecTot->getNumberOfSubstitutions(ids[j], i, 0);
      //totalObs5 += VectorTools::sum(probMapDecDet->getNumberOfSubstitutions(ids[j], i));
    }
    if (tree->isLeaf(ids[j])) cout << tree->getNodeName(ids[j]) << "\t";
    cout << tree->getDistanceToFather(ids[j]) << "\t" << totalReal << "\t" << totalObs1 << "\t" << totalObs2 << "\t" << totalObs3 << "\t" << totalObs4 << "\t" << totalObs5 << endl;
    if (abs(totalReal - totalObs1) / totalReal > 0.1) return 1;
    if (abs(totalReal - totalObs2) / totalReal > 0.1) return 1;
    if (abs(totalReal - totalObs3) / totalReal > 0.1) return 1;
    if (abs(totalReal - totalObs4) / totalReal > 0.1) return 1;
  }
  //2. Detail:
  for (unsigned int j = 0; j < ids.size(); ++j) {
    vector<double> real(4, 0);
    vector<double> obs1(4, 0);
    vector<double> obs2(4, 0);
    for (unsigned int i = 0; i < n; ++i) {
      real += realMapDetailed[i][j];
      //VectorTools::print(real);
      //vector<double> c = probMapDet->getNumberOfSubstitutions(ids[j], i);
      //VectorTools::print(c);
      //obs1 += probMapDet->getNumberOfSubstitutions(ids[j], i);
      //obs2 += probMapDecDet->getNumberOfSubstitutions(ids[j], i);
    }
    if (tree->isLeaf(ids[j])) cout << tree->getNodeName(ids[j]) << "\t";
    cout << tree->getDistanceToFather(ids[j]) << "\t";
    for (unsigned int t = 0; t < 4; ++t) {
      cout << obs1[t] << "/" << real[t] << "\t";
      cout << obs2[t] << "/" << real[t] << "\t";
    }
    cout << endl;
    //if (abs(totalReal - totalObs) / totalReal > 0.1) return 1;
  }
  */

  //-------------
  delete tree;
  delete alphabet;
  delete model;
  delete rdist;
  delete sCountTot;
  delete sCountDnDs;
  delete probMapAna;
  delete probMapTot;
  delete probMapDnDs;
  delete probMapUniTot;
  delete probMapUniDnDs;
  //return (abs(obs - 0.001) < 0.001 ? 0 : 1);
  return 0;
}
Exemplo n.º 4
0
int main() {
  TreeTemplate<Node>* tree = TreeTemplateTools::parenthesisToTree("(((A:0.1, B:0.2):0.3,C:0.1):0.2,(D:0.3,(E:0.2,F:0.05):0.1):0.1);");
  vector<string> seqNames= tree->getLeavesNames();
  vector<int> ids = tree->getNodesId();
  //-------------

  const NucleicAlphabet* alphabet = &AlphabetTools::DNA_ALPHABET;
  FrequenciesSet* rootFreqs = new GCFrequenciesSet(alphabet);
  SubstitutionModel* model = new T92(alphabet, 3.);
  std::vector<std::string> globalParameterNames;
  globalParameterNames.push_back("T92.kappa");
  map<string, string> alias;

  SubstitutionModelSet* modelSet = SubstitutionModelSetTools::createNonHomogeneousModelSet(model, rootFreqs, tree, alias, globalParameterNames);
  //DiscreteDistribution* rdist = new ConstantDistribution(1.0, true);
  //Very difficult to optimize on small datasets:
  DiscreteDistribution* rdist = new GammaDiscreteRateDistribution(4, 1.0);

  size_t nsites = 1000;
  unsigned int nrep = 20;
  size_t nmodels = modelSet->getNumberOfModels();
  vector<double> thetas(nmodels);
  vector<double> thetasEst1(nmodels);
  vector<double> thetasEst2(nmodels);

  for (size_t i = 0; i < nmodels; ++i) {
    double theta = RandomTools::giveRandomNumberBetweenZeroAndEntry(0.99) + 0.005;
    cout << "Theta" << i << " set to " << theta << endl; 
    modelSet->setParameterValue("T92.theta_" + TextTools::toString(i + 1), theta);
    thetas[i] = theta;
  }
  NonHomogeneousSequenceSimulator simulator(modelSet, rdist, tree);
 
  for (unsigned int j = 0; j < nrep; j++) {

    OutputStream* profiler  = new StlOutputStream(new ofstream("profile.txt", ios::out));
    OutputStream* messenger = new StlOutputStream(new ofstream("messages.txt", ios::out));

    //Simulate data:
    auto_ptr<SiteContainer> sites(simulator.simulate(nsites));
    //Now fit model:
    auto_ptr<SubstitutionModelSet> modelSet2(modelSet->clone());
    auto_ptr<SubstitutionModelSet> modelSet3(modelSet->clone());
    RNonHomogeneousTreeLikelihood tl(*tree, *sites.get(), modelSet2.get(), rdist, true, true, false);
    tl.initialize();
    RNonHomogeneousTreeLikelihood tl2(*tree, *sites.get(), modelSet3.get(), rdist, true, true, true);
    tl2.initialize();
   
    unsigned int c1 = OptimizationTools::optimizeNumericalParameters2(
        &tl, tl.getParameters(), 0,
        0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

    unsigned int c2 = OptimizationTools::optimizeNumericalParameters2(
        &tl2, tl2.getParameters(), 0,
        0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

    cout << c1 << ": " << tl.getValue() << "\t" << c2 << ": " << tl2.getValue() << endl;
      
    for (size_t i = 0; i < nmodels; ++i) {
      cout << modelSet2->getModel(i)->getParameter("theta").getValue() << "\t" << modelSet3->getModel(i)->getParameter("theta").getValue() << endl;
      //if (abs(modelSet2->getModel(i)->getParameter("theta").getValue() - modelSet3->getModel(i)->getParameter("theta").getValue()) > 0.1)
      //  return 1;
      thetasEst1[i] +=  modelSet2->getModel(i)->getParameter("theta").getValue();
      thetasEst2[i] +=  modelSet3->getModel(i)->getParameter("theta").getValue();
    }
  }
  thetasEst1 /= static_cast<double>(nrep);
  thetasEst2 /= static_cast<double>(nrep);

  //Now compare estimated values to real ones:
  for (size_t i = 0; i < thetas.size(); ++i) {
     cout << thetas[i] << "\t" << thetasEst1[i] << "\t" << thetasEst2[i] << endl;
     double diff1 = abs(thetas[i] - thetasEst1[i]);
     double diff2 = abs(thetas[i] - thetasEst2[i]);
     if (diff1 > 0.2 || diff2 > 0.2)
        return 1;
  }

  //-------------
  delete tree;
  delete modelSet;
  delete rdist;

  return 0;
}
Exemplo n.º 5
0
int main() {

  TreeTemplate<Node>* tree = TreeTemplateTools::parenthesisToTree("(((A:0.1, B:0.2):0.3,C:0.1):0.2,(D:0.3,(E:0.2,F:0.05):0.1):0.1);");

  vector<string> seqNames= tree->getLeavesNames();
  vector<int> ids = tree->getNodesId();
  //-------------

  const NucleicAlphabet* alphabet = &AlphabetTools::DNA_ALPHABET;
  FrequenciesSet* rootFreqs = new GCFrequenciesSet(alphabet);
  
  SubstitutionModel* model = new T92(alphabet, 3.);
  std::vector<std::string> globalParameterNames;
  globalParameterNames.push_back("T92.kappa");

  //Very difficult to optimize on small datasets:
  DiscreteDistribution* rdist = new GammaDiscreteRateDistribution(4, 1.0);
  
  ParametrizableTree* parTree = new ParametrizableTree(*tree);
  FrequenciesSet* rootFreqs2 = rootFreqs->clone();
  DiscreteDistribution* rdist2 = rdist->clone();
  SubstitutionModel* model2=model->clone();

  map<string, string> alias;

  SubstitutionModelSet* modelSet = SubstitutionModelSetTools::createNonHomogeneousModelSet(model, rootFreqs, tree, alias, globalParameterNames);
  unique_ptr<SubstitutionModelSet> modelSetSim(modelSet->clone());

  NonHomogeneousSubstitutionProcess* subPro= NonHomogeneousSubstitutionProcess::createNonHomogeneousSubstitutionProcess(model2, rdist2, rootFreqs2, parTree, globalParameterNames);

  // Simulation
    
  size_t nsites = 1000;
  unsigned int nrep = 20;
  size_t nmodels = modelSet->getNumberOfModels();
  vector<double> thetas(nmodels);
  vector<double> thetasEst1(nmodels);
  vector<double> thetasEst2(nmodels);
  vector<double> thetasEst1n(nmodels);
  vector<double> thetasEst2n(nmodels);

  for (size_t i = 0; i < nmodels; ++i) {
    double theta = RandomTools::giveRandomNumberBetweenZeroAndEntry(0.99) + 0.005;
    cout << "Theta" << i << " set to " << theta << endl; 
    modelSetSim->setParameterValue("T92.theta_" + TextTools::toString(i + 1), theta);
    //subPro->setParameterValue("T92.theta_" + TextTools::toString(i + 1), theta);
    thetas[i] = theta;
  }

  NonHomogeneousSequenceSimulator simulator(modelSetSim.get(), rdist, tree);

  NonHomogeneousSubstitutionProcess* subPro2 = subPro->clone();

  for (unsigned int j = 0; j < nrep; j++) {

    OutputStream* profiler  = new StlOutputStream(new ofstream("profile.txt", ios::out));
    OutputStream* messenger = new StlOutputStream(new ofstream("messages.txt", ios::out));

    //Simulate data:
    unique_ptr<SiteContainer> sites(simulator.simulate(nsites));

    //Now fit model:
    unique_ptr<SubstitutionModelSet> modelSet2(modelSet->clone());

    RNonHomogeneousTreeLikelihood tl(*tree, *sites.get(), modelSet, rdist, true, true, false);
    tl.initialize();

    RNonHomogeneousTreeLikelihood tl2(*tree, *sites.get(), modelSet2.get(), rdist, true, true, true);
    tl2.initialize();

    SubstitutionProcess* nsubPro=subPro->clone();
    SubstitutionProcess* nsubPro2=subPro2->clone();
    
    RecursiveLikelihoodTreeCalculation* tlComp = new RecursiveLikelihoodTreeCalculation(*sites->clone(), nsubPro, true, false);
    SingleProcessPhyloLikelihood ntl(nsubPro, tlComp, true);

    RecursiveLikelihoodTreeCalculation* tlComp2 = new RecursiveLikelihoodTreeCalculation(*sites->clone(), nsubPro2, true);
    SingleProcessPhyloLikelihood ntl2(nsubPro2, tlComp2, true);

    for (size_t i = 0; i < nmodels; ++i) {
      ntl.setParameterValue("T92.theta_" + TextTools::toString(i + 1), thetas[i]);
      ntl2.setParameterValue("T92.theta_" + TextTools::toString(i + 1), thetas[i]);
    }

    cout << setprecision(10) << "OldTL init: "  << tl.getValue() << "\t" << tl2.getValue() << endl;
    cout << setprecision(10) << "NewTL init: "  << ntl.getValue() << "\t" << ntl2.getValue() << endl;

    unsigned int c1 = OptimizationTools::optimizeNumericalParameters2(
      &tl, tl.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);
    
    
    unsigned int c2 = OptimizationTools::optimizeNumericalParameters2(
      &tl2, tl2.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

    unsigned int nc1 = OptimizationTools::optimizeNumericalParameters2(
      &ntl, ntl.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

    unsigned int nc2 = OptimizationTools::optimizeNumericalParameters2(
      &ntl2, ntl2.getParameters(), 0,
      0.0001, 10000, messenger, profiler, false, false, 1, OptimizationTools::OPTIMIZATION_NEWTON);

    cout << "OldTL: " << c1 << ": " << tl.getValue() << "\t" << c2 << ": " << tl2.getValue() << endl;
    cout << "NewTL: " << nc1 << ": " << ntl.getValue() << "\t" << nc2 << ": " << ntl2.getValue() << endl;

    cout << "Thetas : " << endl;

    for (size_t i = 0; i < nmodels; ++i) {
      //    cerr << modelSet->getModel(i)->getParameter("theta").getValue() << "\t" << modelSet2->getModel(i)->getParameter("theta").getValue();
      
      //      cerr << "\t"  << subPro->getModel(i)->getParameter("theta").getValue() << "\t" << subPro2->getModel(i)->getParameter("theta").getValue() << endl;
      // if (abs(modelSet2->getModel(i)->getParameter("theta").getValue() - modelSet3->getModel(i)->getParameter("theta").getValue()) > 0.1)
      //   return 1;
      thetasEst1[i] +=  modelSet->getModel(i)->getParameter("theta").getValue();
      thetasEst2[i] +=  modelSet2->getModel(i)->getParameter("theta").getValue();
      thetasEst1n[i] +=  dynamic_cast< NonHomogeneousSubstitutionProcess*>(nsubPro)->getModel(i)->getParameter("theta").getValue();
      thetasEst2n[i] +=  dynamic_cast< NonHomogeneousSubstitutionProcess*>(nsubPro2)->getModel(i)->getParameter("theta").getValue();
    }
  }
  thetasEst1 /= static_cast<double>(nrep);
  thetasEst2 /= static_cast<double>(nrep);
  thetasEst1n /= static_cast<double>(nrep);
  thetasEst2n /= static_cast<double>(nrep);

  //Now compare estimated values to real ones:
  cout << "Real" << "\t" << "Est_Old1" << "\t" << "Est_Old2" << "\t";
  cout << "Est_New1" << "\t" << "Est_New2" << endl;
  for (size_t i = 0; i < thetas.size(); ++i) {
    cout << thetas[i] << "\t" << thetasEst1[i] << "\t" << thetasEst2[i] << "\t";
    cout << thetasEst1n[i] << "\t" << thetasEst2n[i] << endl;
     double diff1 = abs(thetas[i] - thetasEst1[i]);
     double diff2 = abs(thetas[i] - thetasEst2[i]);
     double diffn1 = abs(thetas[i] - thetasEst1n[i]);
     double diffn2 = abs(thetas[i] - thetasEst2n[i]);
     if (diff1 > 0.2 || diff2 > 0.2 || diffn1 > 0.2 || diffn2 > 0.2)
       return 1;
  }

  return 0;
}