libopenms-dev 1.11.1-5 / usr / include / OpenMS / TRANSFORMATIONS / FEATUREFINDER / ModelFitter.h

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// Copyright The OpenMS Team -- Eberhard Karls University Tuebingen,
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// $Maintainer: Clemens Groepl $
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#ifndef OPENMS_TRANSFORMATIONS_FEATUREFINDER_MODELFITTER_H
#define OPENMS_TRANSFORMATIONS_FEATUREFINDER_MODELFITTER_H

#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/FeaFiModule.h>
#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/ProductModel.h>
#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/IsotopeModel.h>
#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/ExtendedIsotopeModel.h>
#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/LmaIsotopeModel.h>
#include <OpenMS/TRANSFORMATIONS/FEATUREFINDER/Fitter1D.h>
#include <OpenMS/MATH/STATISTICS/AsymmetricStatistics.h>
#include <OpenMS/MATH/STATISTICS/StatisticFunctions.h>
#include <OpenMS/CONCEPT/Factory.h>

#include <boost/math/special_functions/fpclassify.hpp>

#include <iostream>
#include <fstream>
#include <numeric>
#include <cmath>
#include <vector>
#include <set>

namespace OpenMS
{

  /**
  @brief Tests a group of data points in an LC-MS map for goodness-of-fit with a 2D averagine model.

  The ModelFitter class uses a gaussian or isotope model in m/z and bigauss,
  lmagauss (bigauss with Levenberg-Marquardt) or emg (exponentially modified
  Gaussian with lma optimized parameters) in retention time.

  For the isotope model, we test different charge states and peaks widths.

@todo Fix problem with other peak types than Peak1D and enable the respective tests for FeatureFinderAlgorithmSimple, FeatureFinderAlgorithmSimplest, FeatureFinderAlgorithmWavelet (Clemens)

  @htmlinclude OpenMS_ModelFitter.parameters

  @ingroup FeatureFinder
  */
  template <class PeakType, class FeatureType>
  class ModelFitter :
    public FeaFiModule<PeakType, FeatureType>,
    public FeatureFinderDefs
  {
public:

    /// IndexSet iterator
    typedef IndexSet::const_iterator IndexSetIter;
    /// Quality of a feature
    typedef Feature::QualityType QualityType;
    /// Single coordinate
    typedef Feature::CoordinateType CoordinateType;
    /// Single intensity
    typedef Feature::IntensityType IntensityType;
    /// Isotope charge
    typedef Feature::ChargeType ChargeType;
    /// FeaFiModule
    typedef FeaFiModule<PeakType, FeatureType> Base;
    /// Raw data container type using for the temporary storage of the input data
    typedef std::vector<PeakType> RawDataArrayType;

    enum
    {
      RT = Peak2D::RT,
      MZ = Peak2D::MZ
    };

    /// Constructor
    ModelFitter(const MSExperiment<PeakType> * map, FeatureMap<FeatureType> * features, FeatureFinder * ff) :
      Base(map, features, ff),
      model2D_(),
      mz_stat_(),
      rt_stat_(),
      monoisotopic_mz_(0),
#ifdef DEBUG_FEATUREFINDER
      counter_(1),
#endif
      iso_stdev_first_(0),
      iso_stdev_last_(0),
      iso_stdev_stepsize_(0),
      first_mz_model_(0),
      last_mz_model_(0),
      quality_rt_(0),
      quality_mz_(0)
    {
      this->setName("ModelFitter");

      this->defaults_.setValue("fit_algorithm", "simple", "Fitting algorithm type (internal parameter).", StringList::create("advanced"));
      std::vector<String> fit_opts;
      fit_opts.push_back("simple");
      fit_opts.push_back("simplest");
      fit_opts.push_back("wavelet");
      this->defaults_.setValidStrings("fit_algorithm", fit_opts);

      this->defaults_.setValue("max_iteration", 500, "Maximum number of iterations for fitting with Levenberg-Marquardt algorithm.", StringList::create("advanced"));
      this->defaults_.setMinInt("max_iteration", 1);
      this->defaults_.setValue("deltaAbsError", 0.0001, "Absolute error used by the Levenberg-Marquardt algorithm.", StringList::create("advanced"));
      this->defaults_.setMinFloat("deltaAbsError", 0.0);
      this->defaults_.setValue("deltaRelError", 0.0001, "Relative error used by the Levenberg-Marquardt algorithm.", StringList::create("advanced"));
      this->defaults_.setMinFloat("deltaRelError", 0.0);

      this->defaults_.setValue("tolerance_stdev_bounding_box", 3.0f, "Bounding box has range [minimim of data, maximum of data] enlarged by tolerance_stdev_bounding_box times the standard deviation of the data", StringList::create("advanced"));
      this->defaults_.setMinFloat("tolerance_stdev_bounding_box", 0.0);

      this->defaults_.setValue("intensity_cutoff_factor", 0.05f, "Cutoff peaks with a predicted intensity below intensity_cutoff_factor times the maximal intensity of the model");
      this->defaults_.setMinFloat("intensity_cutoff_factor", 0.0);
      this->defaults_.setMaxFloat("intensity_cutoff_factor", 1.0);

      this->defaults_.setValue("feature_intensity_sum", 1, "Determines what is reported as feature intensity.\n1: the sum of peak intensities;\n0: the maximum intensity of all peaks", StringList::create("advanced"));
      this->defaults_.setMinInt("feature_intensity_sum", 0);
      this->defaults_.setMaxInt("feature_intensity_sum", 1);

      this->defaults_.setValue("min_num_peaks:final", 5, "Minimum number of peaks left after cutoff. If smaller, feature will be discarded.");
      this->defaults_.setMinInt("min_num_peaks:final", 1);
      this->defaults_.setValue("min_num_peaks:extended", 10, "Minimum number of peaks after extension. If smaller, feature will be discarded.");
      this->defaults_.setMinInt("min_num_peaks:extended", 1);
      this->defaults_.setSectionDescription("min_num_peaks", "Required number of peaks for a feature.");

      this->defaults_.setValue("rt:interpolation_step", 0.2f, "Step size in seconds used to interpolate model for RT.");
      this->defaults_.setMinFloat("rt:interpolation_step", 0.0);
      this->defaults_.setSectionDescription("rt", "Model settings in RT dimension.");

      this->defaults_.setValue("mz:interpolation_step", 0.03f, "Interpolation step size for m/z.");
      this->defaults_.setMinFloat("mz:interpolation_step", 0.001);
      this->defaults_.setValue("mz:model_type:first", 1, "Numeric id of first m/z model fitted (usually indicating the charge state), 0 = no isotope pattern (fit a single gaussian).");
      this->defaults_.setMinInt("mz:model_type:first", 0);
      this->defaults_.setValue("mz:model_type:last", 4, "Numeric id of last m/z model fitted (usually indicating the charge state), 0 = no isotope pattern (fit a single gaussian).");
      this->defaults_.setMinInt("mz:model_type:last", 0);
      this->defaults_.setSectionDescription("mz", "Model settings in m/z dimension.");

      this->defaults_.setValue("quality:type", "Correlation", "Type of the quality measure used to assess the fit of model vs data.", StringList::create("advanced"));
      std::vector<String> quality_opts;
      quality_opts.push_back("Correlation");
      quality_opts.push_back("RankCorrelation");
      this->defaults_.setValidStrings("quality:type", quality_opts);
      this->defaults_.setValue("quality:minimum", 0.65f, "Minimum quality of fit, features below this threshold are discarded.");
      this->defaults_.setMinFloat("quality:minimum", 0.0);
      this->defaults_.setMaxFloat("quality:minimum", 1.0);
      this->defaults_.setSectionDescription("quality", "Fitting quality settings.");

      this->defaults_.setValue("isotope_model:stdev:first", 0.04f, "First standard deviation to be considered for isotope model.");
      this->defaults_.setMinFloat("isotope_model:stdev:first", 0.0);
      this->defaults_.setValue("isotope_model:stdev:last", 0.12f, "Last standard deviation to be considered for isotope model.");
      this->defaults_.setMinFloat("isotope_model:stdev:last", 0.0);
      this->defaults_.setValue("isotope_model:stdev:step", 0.04f, "Step size for standard deviations considered for isotope model.");
      this->defaults_.setMinFloat("isotope_model:stdev:step", 0.0);
      this->defaults_.setSectionDescription("isotope_model:stdev", "Instrument resolution settings for m/z dimension.");

      this->defaults_.setValue("isotope_model:averagines:C", 0.04443989f, "Number of C atoms per Dalton of the mass.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:averagines:C", 0.0);
      this->defaults_.setValue("isotope_model:averagines:H", 0.06981572f, "Number of H atoms per Dalton of the mass.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:averagines:H", 0.0);
      this->defaults_.setValue("isotope_model:averagines:N", 0.01221773f, "Number of N atoms per Dalton of the mass.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:averagines:N", 0.0);
      this->defaults_.setValue("isotope_model:averagines:O", 0.01329399f, "Number of O atoms per Dalton of the mass.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:averagines:O", 0.0);
      this->defaults_.setValue("isotope_model:averagines:S", 0.00037525f, "Number of S atoms per Dalton of the mass.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:averagines:S", 0.0);
      this->defaults_.setSectionDescription("isotope_model:averagines", "Averagines are used to approximate the number of atoms (C,H,N,O,S) which a peptide of a given mass contains.");

      this->defaults_.setValue("isotope_model:isotope:trim_right_cutoff", 0.001f, "Cutoff for averagine distribution, trailing isotopes below this relative intensity are not considered.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:isotope:trim_right_cutoff", 0.0);
      this->defaults_.setValue("isotope_model:isotope:maximum", 100, "Maximum number of isotopes being used for the IsotopeModel.", StringList::create("advanced"));
      this->defaults_.setMinInt("isotope_model:isotope:maximum", 1);
      this->defaults_.setValue("isotope_model:isotope:distance", 1.000495f, "Distance between consecutive isotopic peaks.", StringList::create("advanced"));
      this->defaults_.setMinFloat("isotope_model:isotope:distance", 0.0);
      this->defaults_.setSectionDescription("isotope_model", "Settings of the isotope model (m/z).");

      this->defaultsToParam_();
    }

    /// Destructor
    virtual ~ModelFitter()
    {
    }

    /** @brief Sets or fixed the monoisotopic m/z at a specific position.
    * @param mz The monoisotopic m/z that occurres in the current data set. */
    void setMonoIsotopicMass(CoordinateType mz)
    {
      monoisotopic_mz_ = mz;
    }

    /**
        @brief Return next feature

        @exception Exception::UnableToFit is thrown if fitting cannot be performed
        @exception Exception::InvalidParameter if first and last charge to test do not define a range (first<=last)
    */
    Feature fit(const ChargedIndexSet & index_set)
    {
      // Test the number of peaks (not enough peaks to fit)
      if (index_set.size() < UInt(this->param_.getValue("min_num_peaks:extended")))
      {
        String mess = String("Skipping feature, IndexSet size too small: ") + index_set.size();
        throw Exception::UnableToFit(__FILE__, __LINE__, __PRETTY_FUNCTION__, "UnableToFit-IndexSet", mess.c_str());
      }

      // Calculate statistics for mz and rt
      mz_stat_.update
      (
        Internal::IntensityIterator<ModelFitter>(index_set.begin(), this),
        Internal::IntensityIterator<ModelFitter>(index_set.end(), this),
        Internal::MzIterator<ModelFitter>(index_set.begin(), this)
      );
      rt_stat_.update
      (
        Internal::IntensityIterator<ModelFitter>(index_set.begin(), this),
        Internal::IntensityIterator<ModelFitter>(index_set.end(), this),
        Internal::RtIterator<ModelFitter>(index_set.begin(), this)
      );

      // set charge
      if (index_set.charge != 0)
      {
        first_mz_model_ = index_set.charge;
        last_mz_model_ = index_set.charge;
      }

      if (first_mz_model_ > last_mz_model_) throw Exception::InvalidParameter(__FILE__, __LINE__, __PRETTY_FUNCTION__, "ModelFitter::fit(): charge range tested is not valid; check \"model_type:first\" and \"model_type:last\" ");

      // Check charge estimate if charge is not specified by user
#ifdef DEBUG_FEATUREFINDER
      std::cout << "Checking charge state from " << first_mz_model_ << " to " << last_mz_model_ << std::endl;
#endif

      // ** Projection
      doProjectionDim_(RT, index_set, rt_input_data_);
      doProjectionDim_(MZ, index_set, mz_input_data_);
      // Fit rt model
      InterpolationModel * model_rt = 0;
      quality_rt_ = fitRT_(model_rt);
      model2D_.setModel(RT, model_rt);          // Set model in 2D-model

      FeatureMap<Feature> feature_collection;

      for (ChargeType charge = first_mz_model_; charge <= last_mz_model_; ++charge)
      {
        Feature f;
        try
        {
          // "reset" model2D!!
          model2D_.setScale(1.);

          // TODO: intensity scaling should use a more robust estimator (rather than comparing max of data vs. model)

          // Compute model with the best correlation
          // result is in model2D_
          QualityType max_quality = fitMZLoop_(index_set, charge);

          // find peak with highest predicted intensity to use as cutoff
          IntensityType model_max = 0;

          for (IndexSetIter it = index_set.begin(); it != index_set.end(); ++it)
          {
            IntensityType model_int = model2D_.getIntensity(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it)));
            if (model_int > model_max) model_max = model_int;
          }
          model2D_.setCutOff(model_max * Real(this->param_.getValue("intensity_cutoff_factor")));

          // Cutoff low intensities wrt to model maximum -> cutoff independent of scaling
          IndexSet model_set;
          for (IndexSetIter it = index_set.begin(); it != index_set.end(); ++it)
          {
            if (model2D_.isContained(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it))))
            {
              model_set.insert(*it);
            }
          }

          // Print number of selected peaks after cutoff
#ifdef DEBUG_FEATUREFINDER
          std::cout << " Selected " << model_set.size() << " from " << index_set.size() << " peaks.\n";
#endif

          // Calculate intensity scaling
          IntensityType model_sum = 0;
          //IntensityType data_sum = 0;
          IntensityType data_max = 0;
          for (IndexSetIter it = model_set.begin(); it != model_set.end(); ++it)
          {
            IntensityType model_int = model2D_.getIntensity(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it)));
            model_sum += model_int;
            //data_sum += this->getPeakIntensity( *it );
            if (this->getPeakIntensity(*it) > data_max) data_max = this->getPeakIntensity(*it);
          }

          if (model_sum == 0)
          {
            throw Exception::UnableToFit(__FILE__, __LINE__, __PRETTY_FUNCTION__, "UnableToFit-ZeroSum", "Skipping feature, model_sum zero.");
          }

          //std::cout << "data_max: " << data_max << " model_max: " <<  model_max << " model2dscale: " << (data_max / model_max) << std::endl;
          model2D_.setScale(data_max / model_max);              // use max quotient instead of sum quotient

          //std::cout << model2D_.getParameters() << std::endl;

          // Build Feature
          // The feature coordinate in rt dimension is given
          // by the centroid of the rt model whereas the coordinate
          // in mz dimension is equal to the monoisotopic peak.
          f.setModelDescription(ModelDescription<2>(&model2D_));
          f.setOverallQuality(max_quality);
          f.setRT(static_cast<InterpolationModel *>(model2D_.getModel(RT))->getCenter());
          f.setMZ(static_cast<InterpolationModel *>(model2D_.getModel(MZ))->getCenter());

          // set and check convex hull whether m/z is contained or not
          this->addConvexHull(model_set, f);
          if (!f.encloses(f.getRT(), f.getMZ())) f.setMZ(f.getConvexHull().getBoundingBox().minY());

          // feature charge ...
          // if we used a simple Gaussian model to fit the feature, we can't say anything about
          // its charge state. The value 0 indicates that charge state is undetermined.
          if (model2D_.getModel(MZ)->getName() == "LmaIsotopeModel")
          {
            f.setCharge(static_cast<LmaIsotopeModel *>(model2D_.getModel(MZ))->getCharge());
          }
          else if (model2D_.getModel(MZ)->getName() == "IsotopeModel")
          {
            f.setCharge(static_cast<IsotopeModel *>(model2D_.getModel(MZ))->getCharge());
          }
          else if (model2D_.getModel(MZ)->getName() == "ExtendedIsotopeModel")
          {
            f.setCharge(static_cast<ExtendedIsotopeModel *>(model2D_.getModel(MZ))->getCharge());
          }
          else
          {
            f.setCharge(0);
          }

          // feature intensity
          Int const intensity_choice = this->param_.getValue("feature_intensity_sum");
          IntensityType feature_intensity = 0.0;
          if (intensity_choice == 1)
          {
            // intensity of the feature is the sum of all included data points
            for (IndexSetIter it = model_set.begin(); it != model_set.end(); ++it)
            {
              feature_intensity += this->getPeakIntensity(*it);
            }
          }
          else
          {
            // feature intensity is the maximum intensity of all peaks
            for (IndexSetIter it = model_set.begin(); it != model_set.end(); ++it)
            {
              if (this->getPeakIntensity(*it) > feature_intensity)
              {
                feature_intensity = this->getPeakIntensity(*it);
              }
            }
          }

          // set intensity
          f.setIntensity(feature_intensity);

          // set quality (1D)
          f.setQuality(RT, quality_rt_);
          f.setQuality(MZ, quality_mz_);

          //std::cout << "QA: " << f.getOverallQuality() << "  qMZ: " << f.getQuality(1) << " charge: " << f.getCharge() << " stdev: " <<  f.getModelDescription().getParam().getValue("MZ:isotope:stdev")<< std::endl;

#ifdef DEBUG_FEATUREFINDER
          // debug output
          if (this->param_.getValue("fit_algorithm") != "wavelet")
          {
            std::cout << "Feature " << counter_ << ": (" << f.getRT()   << "," << f.getMZ() << ") Qual.: "  << max_quality << std::endl;
          }
          // Save meta data in feature for TOPPView
          f.setMetaValue(3, String(counter_));

          std::cout << "Feature charge: " << f.getCharge() << std::endl;
          std::cout << "Feature quality in mz: " << f.getQuality(MZ) << std::endl;

          // write debug output
          CoordinateType rt = f.getRT();
          CoordinateType mz = f.getMZ();

          // write feature model
          String fname = String("model") + counter_ + "_" + rt + "_" + mz;
          std::ofstream file(fname.c_str());
          for (IndexSetIter it = model_set.begin(); it != model_set.end(); ++it)
          {
            DPosition<2> pos = DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it));
            if (model2D_.isContained(pos))
            {
              file << pos[RT] << " " << pos[MZ] << " " << model2D_.getIntensity(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it))) << "\n";
            }
          }
          file.close();

          // wrote peaks remaining after model fit
          fname = String("feature") + counter_ + "_" + rt + "_" + mz;
          std::ofstream file2(fname.c_str());
          for (IndexSetIter it = model_set.begin(); it != model_set.end(); ++it)
          {
            DPosition<2> pos = DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it));
            if (model2D_.isContained(pos))
            {
              file2 << pos[RT] << " " << pos[MZ] << " " << this->getPeakIntensity(*it) << "\n";
            }
          }
          file2.close();

          // Count features
          ++counter_;

#endif

          feature_collection.push_back(f);
        }         // ! try
        catch (Exception::UnableToFit & /*e*/)
        {
          //std::cout << "CAUGHT!! " << e.getName() << "  " << e.getMessage() << std::endl;
        }
      }

      if (feature_collection.empty())
      {
        String mess = String("Skipping feature, nothing in the feature collection.");
        throw Exception::UnableToFit(__FILE__, __LINE__, __PRETTY_FUNCTION__, "UnableToFit-EmptyFeatureCollection", mess.c_str());
      }

      QualityType best_quality = -std::numeric_limits<QualityType>::max();
      // find best feature
      std::size_t best_idx = 0;
      for (std::size_t idx = 0; idx < feature_collection.size(); ++idx)
      {
        if (best_quality < feature_collection[idx].getOverallQuality())
        {
          best_quality = feature_collection[idx].getOverallQuality();
          best_idx = idx;
        }
      }

      Feature best_feature = feature_collection[best_idx];
      // check some more conditions
      // not enough peaks left for feature

      // fit has too low quality or fit was not possible i.e. because of zero stdev
      if (best_feature.getOverallQuality() < (Real) (this->param_.getValue("quality:minimum")))
      {
        String mess = String("Skipping feature, correlation too small: ") + best_feature.getOverallQuality();
        throw Exception::UnableToFit(__FILE__, __LINE__, __PRETTY_FUNCTION__, "UnableToFit-Correlation", mess.c_str());
      }

      // free unused peaks for best feature
      IndexSet model_set;
      ProductModel<2> * best_model = static_cast<ProductModel<2> *>(best_feature.getModelDescription().createModel());
      for (IndexSetIter it = index_set.begin(); it != index_set.end(); ++it)
      {
        if (best_model->isContained(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it))))
        {
          model_set.insert(*it);
        }
        else
        {
          this->ff_->getPeakFlag(*it) = UNUSED;
        }
      }
      delete best_model;
      if (model_set.size() < (UInt) (this->param_.getValue("min_num_peaks:final")))
      {
        throw Exception::UnableToFit(__FILE__, __LINE__, __PRETTY_FUNCTION__, "UnableToFit-FinalSet", String("Skipping feature, IndexSet size after cutoff too small: ") + model_set.size());
      }

      // add all but the best feature to the suboptimal ones
      for (std::size_t idx = 0; idx < feature_collection.size(); ++idx)
      {
        if (idx == best_idx) continue;
        best_feature.getSubordinates().push_back(feature_collection[idx]);
      }

      // return "best" feature
      return best_feature;

    }

protected:

    virtual void updateMembers_()
    {
      algorithm_ = this->param_.getValue("fit_algorithm");

      max_iteration_ = this->param_.getValue("max_iteration");
      deltaAbsError_ = this->param_.getValue("deltaAbsError");
      deltaRelError_ = this->param_.getValue("deltaRelError");

      tolerance_stdev_box_ = this->param_.getValue("tolerance_stdev_bounding_box");
      max_isotope_ = this->param_.getValue("isotope_model:isotope:maximum");

      interpolation_step_mz_ = this->param_.getValue("mz:interpolation_step");
      interpolation_step_rt_ = this->param_.getValue("rt:interpolation_step");

      iso_stdev_first_ = this->param_.getValue("isotope_model:stdev:first");
      iso_stdev_last_ = this->param_.getValue("isotope_model:stdev:last");
      iso_stdev_stepsize_ = this->param_.getValue("isotope_model:stdev:step");

      first_mz_model_ = (Int) this->param_.getValue("mz:model_type:first");
      last_mz_model_ = (Int) this->param_.getValue("mz:model_type:last");
    }

    /// main fit loop
    QualityType fitMZLoop_(const ChargedIndexSet & set, const ChargeType & charge)
    {

      // Fit mz model ... test different charge states and stdevs
      QualityType max_quality_mz = -std::numeric_limits<QualityType>::max();

      InterpolationModel * best_model_mz = 0;
      for (Real stdev = iso_stdev_first_; stdev <= iso_stdev_last_; stdev += iso_stdev_stepsize_)
      {
        isotope_stdev_ = stdev;

        InterpolationModel * model_mz = 0;
        quality_mz_ = fitMZ_(model_mz, charge);


        if (quality_mz_ > max_quality_mz)
        {
          max_quality_mz = quality_mz_;
          if (best_model_mz) delete best_model_mz;
          best_model_mz = model_mz;
        }
        else
        {
          delete model_mz;
        }
      }

      model2D_.setModel(MZ, best_model_mz);                 // Set model in 2D-model

      quality_mz_ = max_quality_mz;

      // return overall quality
      return evaluate_(set);
    }

    /// evaluate 2d-model
    QualityType evaluate_(const IndexSet & set) const
    {
      QualityType quality = 0.0;

      // Calculate the pearson correlation coefficient for the values in [begin_a, end_a) and [begin_b, end_b)
      if (algorithm_ != "")
      {
        std::vector<Real> real_data;
        real_data.reserve(set.size());
        std::vector<Real> model_data;
        model_data.reserve(set.size());

        for (IndexSet::const_iterator it = set.begin(); it != set.end(); ++it)
        {
          real_data.push_back(this->getPeakIntensity(*it));
          model_data.push_back(model2D_.getIntensity(DPosition<2>(this->getPeakRt(*it), this->getPeakMz(*it))));
        }

        if (this->param_.getValue("quality:type") == "RankCorrelation")
        {
          quality = Math::rankCorrelationCoefficient(real_data.begin(), real_data.end(), model_data.begin(), model_data.end());
        }
        else quality = Math::pearsonCorrelationCoefficient(real_data.begin(), real_data.end(), model_data.begin(), model_data.end());
      }

      if (boost::math::isnan(quality)) quality = -1.0;

      return quality;
    }

    /// 1d fit in RT
    QualityType fitRT_(InterpolationModel * & model) const
    {
      QualityType quality;
      Param param;
      Fitter1D * fitter;

      if (algorithm_ == "simplest")     // Fit with BiGauss
      {
        param.setValue("tolerance_stdev_bounding_box", tolerance_stdev_box_);
        param.setValue("statistics:mean", rt_stat_.mean());
        param.setValue("statistics:variance", rt_stat_.variance());
        param.setValue("statistics:variance1", rt_stat_.variance1());
        param.setValue("statistics:variance2", rt_stat_.variance2());
        param.setValue("interpolation_step", interpolation_step_rt_);

        fitter = Factory<Fitter1D>::create("BiGaussFitter1D");
      }
      else       // Fit with EMG (LM optimization)
      {
        param.setValue("tolerance_stdev_bounding_box", tolerance_stdev_box_);
        param.setValue("statistics:mean", rt_stat_.mean());
        param.setValue("statistics:variance", rt_stat_.variance());
        param.setValue("interpolation_step", interpolation_step_rt_);
        param.setValue("max_iteration", max_iteration_);
        param.setValue("deltaAbsError", deltaAbsError_);
        param.setValue("deltaRelError", deltaRelError_);

        fitter = Factory<Fitter1D>::create("EmgFitter1D");
      }

      // Set parameter for fitter
      fitter->setParameters(param);

      // Construct model for rt
      quality = fitter->fit1d(rt_input_data_, model);
      // Check quality
      if (boost::math::isnan(quality)) quality = -1.0;

      delete(fitter);

      return quality;
    }

    /// 1d fit in MZ
    QualityType fitMZ_(InterpolationModel * & model, const ChargeType & charge) const
    {
      QualityType quality;
      Param param;
      Fitter1D * fitter;

      param.setValue("tolerance_stdev_bounding_box", tolerance_stdev_box_);
      param.setValue("statistics:mean", mz_stat_.mean());
      param.setValue("statistics:variance", mz_stat_.variance());
      param.setValue("interpolation_step", interpolation_step_mz_);

      if (monoisotopic_mz_ != 0)         // monoisotopic mz is known
      {
        param.setValue("statistics:mean", monoisotopic_mz_);
      }

      if (charge != 0)       // charge is not zero
      {
        param.setValue("charge", charge);
        param.setValue("isotope:stdev", isotope_stdev_);
        param.setValue("isotope:maximum", max_isotope_);
        fitter = Factory<Fitter1D>::create("IsotopeFitter1D");
      }
      else       // charge is zero
      {
        if (algorithm_ == "simplest")       // Fit with GaussModel
        {
          param.setValue("charge", charge);
          param.setValue("isotope:stdev", isotope_stdev_);
          param.setValue("isotope:maximum", max_isotope_);
          fitter = Factory<Fitter1D>::create("IsotopeFitter1D");
        }
        else         // Fit with LmaGaussModel
        {
          param.setValue("max_iteration", max_iteration_);
          param.setValue("deltaAbsError", deltaAbsError_);
          param.setValue("deltaRelError", deltaRelError_);
          fitter = Factory<Fitter1D>::create("LmaGaussFitter1D");
        }
      }

      // Set parameter for fitter
      fitter->setParameters(param);

      // Construct model for mz
      quality = fitter->fit1d(mz_input_data_, model);

      //std::cout << "model after fitting: " << model->getParameters() << std::endl << std::endl;

      // Check quality
      if (boost::math::isnan(quality)) quality = -1.0;

      delete(fitter);

      return quality;
    }

    /// Project the raw data into 1-dim array
    void doProjectionDim_(const Int dim, const ChargedIndexSet & index_set, RawDataArrayType & set) const
    {

      if (algorithm_ != "")
      {
        std::map<CoordinateType, CoordinateType> data_map;

        if (dim == MZ)
        {
          for (IndexSet::const_iterator it = index_set.begin(); it != index_set.end(); ++it)
          {
            data_map[this->getPeakMz(*it)] += this->getPeakIntensity(*it);
          }
        }
        else
        {
          for (IndexSet::const_iterator it = index_set.begin(); it != index_set.end(); ++it)
          {
            data_map[this->getPeakRt(*it)] += this->getPeakIntensity(*it);
          }
        }

        // Copy the raw data into set
        set.resize(data_map.size());
        std::map<CoordinateType, CoordinateType>::iterator it;
        UInt i = 0;
        for (it = data_map.begin(); it != data_map.end(); ++it, ++i)
        {
          set[i].setPosition((*it).first);
          set[i].setIntensity((*it).second);
        }

      }

    }

    /// 2D model
    ProductModel<2> model2D_;
    /// statistics for mz
    Math::BasicStatistics<> mz_stat_;
    /// statistics for rt
    Math::AsymmetricStatistics<> rt_stat_;
    /// mz raw data
    RawDataArrayType mz_input_data_;
    /// rt raw data
    RawDataArrayType rt_input_data_;
    /// tolerance used for bounding box
    CoordinateType tolerance_stdev_box_;
    /// monoistopic mass
    CoordinateType monoisotopic_mz_;
#ifdef DEBUG_FEATUREFINDER
    /// counts features (used for debug output only)
    UInt counter_;
#endif
    /// interpolation step size (in m/z)
    CoordinateType interpolation_step_mz_;
    /// interpolation step size (in retention time)
    CoordinateType interpolation_step_rt_;
    /// maximum isotopic rank to be considered
    Int max_isotope_;
    /// first stdev
    CoordinateType iso_stdev_first_;
    /// last stdev
    CoordinateType iso_stdev_last_;
    /// step size
    CoordinateType iso_stdev_stepsize_;
    /// first mz model (0=Gaussian, 1....n = charge )
    Int first_mz_model_;
    /// last mz model
    Int last_mz_model_;
    /// isotope stdev
    CoordinateType isotope_stdev_;
    /// algorithm
    String algorithm_;
    /// Maximum number of iterations
    Int max_iteration_;
    /** Test for the convergence of the sequence by comparing the last iteration step dx with the absolute error epsabs and relative error epsrel to the current position x */
    /// Absolute error
    CoordinateType deltaAbsError_;
    /// Relative error
    CoordinateType deltaRelError_;
    /// statistics
    Math::BasicStatistics<> basic_stat_;
    /// fit quality in RT dimension
    QualityType quality_rt_;
    /// fit quality in MZ dimension
    QualityType quality_mz_;

private:

    /// Not implemented
    ModelFitter();
    /// Not implemented
    ModelFitter & operator=(const ModelFitter &);
    /// Not implemented
    ModelFitter(const ModelFitter &);

  };

}

#endif // OPENMS_TRANSFORMATIONS_FEATUREFINDER_MODELFITTER_H