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// --------------------------------------------------------------------------
//                   OpenMS -- Open-Source Mass Spectrometry
// --------------------------------------------------------------------------
// Copyright The OpenMS Team -- Eberhard Karls University Tuebingen,
// ETH Zurich, and Freie Universitaet Berlin 2002-2013.
//
// This software is released under a three-clause BSD license:
//  * Redistributions of source code must retain the above copyright
//    notice, this list of conditions and the following disclaimer.
//  * 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.
//  * Neither the name of any author or any participating institution
//    may be used to endorse or promote products derived from this software
//    without specific prior written permission.
// For a full list of authors, refer to the file AUTHORS.
// --------------------------------------------------------------------------
// 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 ANY OF THE AUTHORS OR THE CONTRIBUTING
// INSTITUTIONS 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.
//
// --------------------------------------------------------------------------
// $Maintainer: Alexandra Zerck $
// $Authors: $
// --------------------------------------------------------------------------

#ifndef OPENMS_TRANSFORMATIONS_RAW2PEAK_TWODOPTIMIZATION_H
#define OPENMS_TRANSFORMATIONS_RAW2PEAK_TWODOPTIMIZATION_H

//#define DEBUG_2D
#undef DEBUG_2D

#ifdef DEBUG_2D
#include <iostream>
#include <fstream>
#endif

#include <vector>
#include <utility>
#include <cmath>
#include <set>

#include <OpenMS/TRANSFORMATIONS/RAW2PEAK/PeakShape.h>
#include <OpenMS/TRANSFORMATIONS/RAW2PEAK/OptimizePeakDeconvolution.h>
#include <OpenMS/KERNEL/MSExperiment.h>
#include <OpenMS/KERNEL/MSSpectrum.h>
#include <OpenMS/KERNEL/PeakIndex.h>
#include <OpenMS/CONCEPT/Exception.h>
#include <OpenMS/DATASTRUCTURES/IsotopeCluster.h>
#include <OpenMS/DATASTRUCTURES/DefaultParamHandler.h>

#ifndef OPENMS_SYSTEM_STOPWATCH_H
#endif

#include <boost/math/special_functions/acosh.hpp>
#include <gsl/gsl_vector.h>
#include <gsl/gsl_multifit_nlin.h>
#include <gsl/gsl_blas.h>
#include <OpenMS/TRANSFORMATIONS/RAW2PEAK/OptimizePick.h>
#include <OpenMS/TRANSFORMATIONS/RAW2PEAK/PeakShape.h>

namespace OpenMS
{
  /**
    @brief This class provides the two-dimensional optimization of the picked peak parameters.

    Given the picked peaks, this class optimizes the peak parameters of each isotope pattern using
    a non-linear optimization. The peaks of adjacent scans are adjusted to achieve that a peak occuring in
    several scans has always the same m/z position. For the optimization the Levenberg-Marquardt algorithm
    provided from the GSL is used. The optimized parameters are the m/z values,
    the left and right width, which shall be equal for a peak in all scans,
    and the peaks' heights.

    @todo Works only with defined types due to pointers to the data in the optimization namespace! Change that or remove templates (Alexandra)

    @htmlinclude OpenMS_TwoDOptimization.parameters
  */
  class OPENMS_DLLAPI TwoDOptimization :
    public DefaultParamHandler
  {
public:

    /// Constructor
    TwoDOptimization();

    /// Copy constructor
    TwoDOptimization(const TwoDOptimization& opt);

    /// Destructor
    virtual ~TwoDOptimization(){}

    /// Assignment operator
    TwoDOptimization& operator=(const TwoDOptimization& opt);


    ///Non-mutable access to the matching epsilon
    inline DoubleReal getMZTolerance() const {return tolerance_mz_; }
    ///Mutable access to the matching epsilon
    inline void setMZTolerance(DoubleReal tolerance_mz)
    {
      tolerance_mz_ = tolerance_mz;
      param_.setValue("2d:tolerance_mz", tolerance_mz);
    }

    ///Non-mutable access to the maximal peak distance in a cluster
    inline DoubleReal getMaxPeakDistance() const {return max_peak_distance_; }
    ///Mutable access to the maximal peak distance in a cluster
    inline void setMaxPeakDistance(DoubleReal max_peak_distance)
    {
      max_peak_distance_ = max_peak_distance;
      param_.setValue("2d:max_peak_distance", max_peak_distance);
    }

    ///Non-mutable access to the maximal absolute error
    inline DoubleReal getMaxAbsError() const {return eps_abs_; }
    ///Mutable access to the  maximal absolute error
    inline void setMaxAbsError(DoubleReal eps_abs)
    {
      eps_abs_ = eps_abs;
      param_.setValue("delta_abs_error", eps_abs);
    }

    ///Non-mutable access to the maximal relative error
    inline DoubleReal getMaxRelError() const {return eps_rel_; }
    ///Mutable access to the maximal relative error
    inline void setMaxRelError(DoubleReal eps_rel)
    {
      eps_rel_ = eps_rel;
      param_.setValue("delta_rel_error", eps_rel);
    }

    ///Non-mutable access to the maximal number of iterations
    inline UInt getMaxIterations() const {return max_iteration_; }
    ///Mutable access to the  maximal number of iterations
    inline void setMaxIterations(UInt max_iteration)
    {
      max_iteration_ = max_iteration;
      param_.setValue("iterations", max_iteration);
    }

    ///Non-mutable access to the minimal number of adjacent scans
    inline const OptimizationFunctions::PenaltyFactorsIntensity& getPenalties() const {return penalties_; }
    ///Mutable access to the minimal number of adjacent scans
    inline void setPenalties(OptimizationFunctions::PenaltyFactorsIntensity& penalties)
    {
      penalties_ = penalties;
      param_.setValue("penalties:position", penalties.pos);
      param_.setValue("penalties:height", penalties.height);
      param_.setValue("penalties:left_width", penalties.lWidth);
      param_.setValue("penalties:right_width", penalties.rWidth);
    }

    /**
        @brief Find two dimensional peak clusters and optimize their peak parameters

        @note For the peak spectra, the following meta data arrays (see MSSpectrum) have to be present and have to be named just as listed here:
        - intensity (index:1)
        - leftWidth (index:3)
        - rightWidth (index:4)
        - peakShape (index:5)

        @param first begin of the raw data spectra iterator range
        @param last end of the raw data spectra interator range
        @param ms_exp peak map corresponding to the raw data in the range from @p first to @p last
        @param real2D flag if the optimization should be two dimensional or on each scan separately
        @exception Exception::IllegalArgument is thrown if required meta information from peak picking is missing (area, shape, left width, right width) or if the input data is invalid in some other way

    */
    template <typename InputSpectrumIterator, typename OutputPeakType>
    void optimize(InputSpectrumIterator first,
                  InputSpectrumIterator last,
                  MSExperiment<OutputPeakType>& ms_exp, bool real2D = true);


protected:
    /// Helper struct (contains the size of an area and a raw data container)
    struct Data
    {
      std::vector<std::pair<SignedSize, SignedSize> > signal2D;
      std::multimap<DoubleReal, IsotopeCluster>::iterator iso_map_iter;
      Size total_nr_peaks;
      std::map<Int, std::vector<PeakIndex> > matching_peaks;
      MSExperiment<> picked_peaks;
      MSExperiment<Peak1D>::ConstIterator raw_data_first;
      OptimizationFunctions::PenaltyFactorsIntensity penalties;
      std::vector<DoubleReal> positions;
      std::vector<DoubleReal> signal;
    };

    /// stores the retention time of each isotopic cluster
    std::multimap<DoubleReal, IsotopeCluster> iso_map_;

    /// Pointer to the current region
    std::multimap<DoubleReal, IsotopeCluster>::const_iterator curr_region_;

    /// upper bound for distance between two peaks belonging to the same region
    DoubleReal max_peak_distance_;

    /// threshold for the difference in the peak position of two matching peaks
    DoubleReal tolerance_mz_;

    /// Indices of peaks in the adjacent scans matching peaks in the scan with no. ref_scan
    //  std::map<Int, std::vector<MSExperiment<>::SpectrumType::Iterator > > matching_peaks_;
    std::map<Int, std::vector<PeakIndex> > matching_peaks_;


    /// Convergence Parameter: Maximal absolute error
    DoubleReal eps_abs_;

    /// Convergence Parameter: Maximal relative error
    DoubleReal eps_rel_;

    /// Convergence Parameter: Maximal number of iterations
    UInt max_iteration_;

    /// Optimization considering all scans of a cluster or optimization of each scan separately
    bool real_2D_;


    /// Penalty factors for some parameters in the optimization
    OptimizationFunctions::PenaltyFactorsIntensity penalties_;


    /**
   @name Functions provided to the gsl Levenberg-Marquardt
    */
    //@{
    /// Function computing estimated signal and its deviation to the experimental signal*/
    static Int residual2D_(const gsl_vector* x, void* params, gsl_vector* f);
    /// Function computing the Jacobian */
    static Int jacobian2D_(const gsl_vector* x, void* params, gsl_matrix* J);
    /// Function that calls residual2D and jacobian2D*/
    static Int evaluate2D_(const gsl_vector* x, void* params, gsl_vector* f, gsl_matrix* J);


    /**
         @name Auxiliary Functions for the search of matching regions
    */
    //@{
    std::vector<DoubleReal>::iterator searchInScan_(std::vector<DoubleReal>::iterator scan_begin,
                                                    std::vector<DoubleReal>::iterator scan_end,
                                                    DoubleReal current_mz);

    /** Performs 2D optimization of all regions */
    template <typename InputSpectrumIterator, typename OutputPeakType>
    void optimizeRegions_(InputSpectrumIterator& first,
                          InputSpectrumIterator& last,
                          MSExperiment<OutputPeakType>& ms_exp);

    /** Performs an optimization of all regions by calling OptimizePick */
    template <typename InputSpectrumIterator, typename OutputPeakType>
    void optimizeRegionsScanwise_(InputSpectrumIterator& first,
                                  InputSpectrumIterator& last,
                                  MSExperiment<OutputPeakType>& ms_exp);


    /// Get the indices of the first and last raw data point of this region
    template <typename InputSpectrumIterator, typename OutputPeakType>
    void getRegionEndpoints_(MSExperiment<OutputPeakType>& exp,
                             InputSpectrumIterator& first,
                             InputSpectrumIterator& last,
                             Size iso_map_idx,
                             DoubleReal noise_level,
                             TwoDOptimization::Data& d);

    /// Identify matching peak in a peak cluster
    void findMatchingPeaks_(std::multimap<DoubleReal, IsotopeCluster>::iterator& it,
                            MSExperiment<>& ms_exp);

    //@}

    /// update members method from DefaultParamHandler to update the members
    void updateMembers_();
  };


  template <typename InputSpectrumIterator, typename OutputPeakType>
  void TwoDOptimization::optimize(InputSpectrumIterator first, InputSpectrumIterator last, MSExperiment<OutputPeakType>& ms_exp, bool real2D)
  {
    //#define DEBUG_2D
    //check if the input maps have the same number of spectra
    if ((UInt)distance(first, last) != ms_exp.size())
    {
      throw Exception::IllegalArgument(__FILE__, __LINE__, __PRETTY_FUNCTION__, "Error in Two2Optimization: Raw and peak map do not have the same number of spectra");
    }
    //do nothing if there are no scans
    if (ms_exp.empty())
    {
      return;
    }
    //check if required meta data arrays are present (for each scan)
    for (Size i = 0; i < ms_exp.size(); ++i)
    {
      //check if enough meta data arrays are present
      if (ms_exp[i].getFloatDataArrays().size() < 6)
      {
        throw Exception::IllegalArgument(__FILE__, __LINE__, __PRETTY_FUNCTION__, "Error in Two2Optimization: Not enough meta data arrays present (1:area, 5:shape, 3:left width, 4:right width)");
      }
      bool area = ms_exp[i].getFloatDataArrays()[1].getName() == "maximumIntensity";
      bool wleft = ms_exp[i].getFloatDataArrays()[3].getName() == "leftWidth";
      bool wright = ms_exp[i].getFloatDataArrays()[4].getName() == "rightWidth";
      bool shape = ms_exp[i].getFloatDataArrays()[5].getName() == "peakShape";

      if (!area || !wleft || !wright || !shape)
      {
        throw Exception::IllegalArgument(__FILE__, __LINE__, __PRETTY_FUNCTION__, "Error in Two2Optimization: One or several meta data arrays missing (1:intensity, 5:shape, 3:left width, 4:right width)");
      }
    }
    real_2D_ = real2D;
    typedef typename InputSpectrumIterator::value_type InputSpectrumType;
    typedef typename InputSpectrumType::value_type PeakType;
    typedef MSSpectrum<PeakType> SpectrumType;

    typename MSExperiment<OutputPeakType>::Iterator ms_exp_it = ms_exp.begin();
    typename MSExperiment<OutputPeakType>::Iterator ms_exp_it_end = ms_exp.end();
    if (ms_exp.empty())
    {
      std::cout << "empty experiment" << std::endl;
      return;
    }
    // stores the monoisotopic peaks of isotopic clusters
    std::vector<DoubleReal> iso_last_scan;
    std::vector<DoubleReal> iso_curr_scan;
    std::vector<std::multimap<DoubleReal, IsotopeCluster>::iterator> clusters_last_scan;
    std::vector<std::multimap<DoubleReal, IsotopeCluster>::iterator> clusters_curr_scan;
    std::multimap<DoubleReal, IsotopeCluster>::iterator cluster_iter;
    DoubleReal current_rt = ms_exp_it->getRT(), last_rt  = 0;

    // retrieve values for accepted peaks distances
    max_peak_distance_ = param_.getValue("2d:max_peak_distance");
    DoubleReal tolerance_mz = param_.getValue("2d:tolerance_mz");

    UInt current_charge     = 0; // charge state of the current isotopic cluster
    DoubleReal mz_in_hash   = 0; // used as reference to the current isotopic peak

    // sweep through scans
    for (UInt curr_scan = 0; ms_exp_it + curr_scan != ms_exp_it_end; ++curr_scan)
    {
      Size nr_peaks_in_scan = (ms_exp_it + curr_scan)->size();
      if (nr_peaks_in_scan == 0)
        continue;

      //last_rt = current_rt;
      current_rt = (ms_exp_it + curr_scan)->getRT();
      typename MSExperiment<OutputPeakType>::SpectrumType::Iterator peak_it  = (ms_exp_it + curr_scan)->begin();

      // copy cluster information of least scan
      iso_last_scan = iso_curr_scan;
      iso_curr_scan.clear();
      clusters_last_scan = clusters_curr_scan;
      clusters_curr_scan.clear();

#ifdef DEBUG_2D
      std::cout << "Next scan with rt: " << current_rt << std::endl;
      std::cout << "Next scan, rt = " << current_rt << " last_rt: " << last_rt << std::endl;
      std::cout << "---------------------------------------------------------------------------" << std::endl;
#endif
      MSSpectrum<PeakType> s;
      s.setRT(current_rt);
      // check if there were scans in between
      if (last_rt == 0 || // are we in the first scan
          ((lower_bound(first, last, s, typename SpectrumType::RTLess()) - 1)->getRT() == last_rt))
      {


        for (UInt curr_peak = 0; curr_peak < (ms_exp_it + curr_scan)->size() - 1; ++curr_peak)
        {

          // store the m/z of the current peak
          DoubleReal curr_mz         = (peak_it + curr_peak)->getMZ();
          DoubleReal dist2nextpeak = (peak_it + curr_peak + 1)->getMZ() - curr_mz;

          if (dist2nextpeak <= max_peak_distance_) // one single peak without neighbors isn't optimized
          {
#ifdef DEBUG_2D
            std::cout << "Isotopic pattern found ! " << std::endl;
            std::cout << "We are at: " << (peak_it + curr_peak)->getMZ()  << " " << curr_mz << std::endl;
#endif
            if (!iso_last_scan.empty()) // Did we find any isotopic cluster in the last scan?
            {
              std::sort(iso_last_scan.begin(), iso_last_scan.end());
              // there were some isotopic clustures in the last scan...
              std::vector<DoubleReal>::iterator it =
                searchInScan_(iso_last_scan.begin(), iso_last_scan.end(), curr_mz);

              DoubleReal delta_mz = fabs(*it - curr_mz);
              //std::cout << delta_mz << " "<< tolerance_mz << std::endl;
              if (delta_mz > tolerance_mz) // check if first peak of last cluster is close enough
              {
                mz_in_hash = curr_mz; // update current hash key

                // create new isotopic cluster
// #ifdef DEBUG_2D
//                                                      std::cout << "Last peak cluster too far, creating new cluster at "<<curr_mz << std::endl;
// #endif
                IsotopeCluster new_cluster;
                new_cluster.peaks.charge  = current_charge;
                new_cluster.scans.push_back(curr_scan);
                cluster_iter = iso_map_.insert(std::pair<DoubleReal, IsotopeCluster>(mz_in_hash, new_cluster));

              }
              else
              {
// //#ifdef DEBUG_2D
//                                                      std::cout << "Found neighbouring peak with distance (m/z) " << delta_mz << std::endl;
// //#endif
                cluster_iter = clusters_last_scan[distance(iso_last_scan.begin(), it)];

                // check whether this scan is already contained
                if (find(cluster_iter->second.scans.begin(), cluster_iter->second.scans.end(), curr_scan)
                    == cluster_iter->second.scans.end())
                {
                  cluster_iter->second.scans.push_back(curr_scan);
                }

//                                                      //#ifdef DEBUG_2D
//                                                      std::cout << "Cluster with " << cluster_iter->second.peaks.size()
//                                                                          << " peaks retrieved." << std::endl;
//                                                      //#endif
              }

            }
            else                             // last scan did not contain any isotopic cluster
            {
//                                              //#ifdef DEBUG_2D
//                                              std::cout << "Last scan was empty => creating new cluster." << std::endl;
//                                              std::cout << "Creating new cluster at m/z: " << curr_mz << std::endl;
//                                              //#endif

              mz_in_hash = curr_mz; // update current hash key

              // create new isotopic cluster
              IsotopeCluster new_cluster;
              new_cluster.peaks.charge  = current_charge;
              new_cluster.scans.push_back(curr_scan);
              cluster_iter = iso_map_.insert(std::pair<DoubleReal, IsotopeCluster>(mz_in_hash, new_cluster));

            }

//                                      //#ifdef DEBUG_2D
//                                      std::cout << "Storing found peak in current isotopic cluster" << std::endl;
//                                      //#endif



            cluster_iter->second.peaks.insert(std::pair<UInt, UInt>(curr_scan, curr_peak));

            iso_curr_scan.push_back(mz_in_hash);
            clusters_curr_scan.push_back(cluster_iter);
            ++curr_peak;

            cluster_iter->second.peaks.insert(std::pair<UInt, UInt>(curr_scan, curr_peak));
            iso_curr_scan.push_back((peak_it + curr_peak)->getMZ());
            clusters_curr_scan.push_back(cluster_iter);

            // check distance to next peak
            if ((curr_peak + 1) >= nr_peaks_in_scan)
              break;
            dist2nextpeak = (peak_it + curr_peak + 1)->getMZ() -  (peak_it + curr_peak)->getMZ();


            // loop until end of isotopic pattern in this scan
            while (dist2nextpeak <= max_peak_distance_
                  &&  curr_peak < (nr_peaks_in_scan - 1))
            {
              cluster_iter->second.peaks.insert(std::pair<UInt, UInt>(curr_scan, curr_peak + 1)); // save peak in cluster
              iso_curr_scan.push_back((peak_it + curr_peak + 1)->getMZ());
              clusters_curr_scan.push_back(cluster_iter);
              // std::cout << "new enter'd: "<<(peak_it+curr_peak+1)->getMZ()<<" im while"<<std::endl;
              ++curr_peak;
              if (curr_peak >= nr_peaks_in_scan - 1)
                break;
              dist2nextpeak = (peak_it + curr_peak + 1)->getMZ() -  (peak_it + curr_peak)->getMZ(); // get distance to next peak


            } // end while(...)



          } // end of if (dist2nextpeak <= max_peak_distance_)
          else
          {
            if (!iso_last_scan.empty()) // Did we find any isotopic cluster in the last scan?
            {
              std::sort(iso_last_scan.begin(), iso_last_scan.end());
              // there were some isotopic clusters in the last scan...
              std::vector<DoubleReal>::iterator it =
                searchInScan_(iso_last_scan.begin(), iso_last_scan.end(), curr_mz);

              DoubleReal delta_mz = fabs(*it - curr_mz);
              // std::cout << delta_mz << " "<< tolerance_mz << std::endl;
              if (delta_mz > tolerance_mz) // check if first peak of last cluster is close enough
              {
                mz_in_hash = curr_mz; // update current hash key

                // create new isotopic cluster
//                                                      //#ifdef DEBUG_2D
//                                                      std::cout << "Last peak cluster too far, creating new cluster at "<<curr_mz << std::endl;
//                                                      //#endif
                IsotopeCluster new_cluster;
                new_cluster.peaks.charge  = current_charge;
                new_cluster.scans.push_back(curr_scan);
                cluster_iter = iso_map_.insert(std::pair<DoubleReal, IsotopeCluster>(mz_in_hash, new_cluster));

              }
              else
              {
//                                                      //#ifdef DEBUG_2D
//                                                      std::cout << "Found neighbouring peak with distance (m/z) " << delta_mz << std::endl;
//                                                      //#endif
                cluster_iter = clusters_last_scan[distance(iso_last_scan.begin(), it)];

                // check whether this scan is already contained
                if (find(cluster_iter->second.scans.begin(), cluster_iter->second.scans.end(), curr_scan)
                    == cluster_iter->second.scans.end())
                {
                  cluster_iter->second.scans.push_back(curr_scan);
                }

//                                                      //#ifdef DEBUG_2D
//                                                      std::cout << "Cluster with " << cluster_iter->second.peaks.size()
//                                                                          << " peaks retrieved." << std::endl;
//                                                      //#endif
              }

            }
            else                             // last scan did not contain any isotopic cluster
            {
//                                              //#ifdef DEBUG_2D
//                                              std::cout << "Last scan was empty => creating new cluster." << std::endl;
//                                              std::cout << "Creating new cluster at m/z: " << curr_mz << std::endl;
//                                              //#endif

              mz_in_hash = curr_mz; // update current hash key

              // create new isotopic cluster
              IsotopeCluster new_cluster;
              new_cluster.peaks.charge  = current_charge;
              new_cluster.scans.push_back(curr_scan);
              cluster_iter = iso_map_.insert(std::pair<DoubleReal, IsotopeCluster>(mz_in_hash, new_cluster));

            }

//                                      //#ifdef DEBUG_2D
//                                      std::cout << "Storing found peak in current isotopic cluster" << std::endl;
//                                      //#endif



            cluster_iter->second.peaks.insert(std::pair<UInt, UInt>(curr_scan, curr_peak));

            iso_curr_scan.push_back(mz_in_hash);
            clusters_curr_scan.push_back(cluster_iter);


          }

          current_charge = 0; // reset charge
        } // end for (...)
      }
      last_rt = current_rt;
    }
    curr_region_ = iso_map_.begin();
#ifdef DEBUG_2D
    std::cout << iso_map_.size() << " isotopic clusters were found ! " << std::endl;
#endif

    if (real_2D_)
      optimizeRegions_(first, last, ms_exp);
    else
      optimizeRegionsScanwise_(first, last, ms_exp);
    //#undef DEBUG_2D
  }

  template <typename InputSpectrumIterator, typename OutputPeakType>
  void TwoDOptimization::optimizeRegions_(InputSpectrumIterator& first,
                                          InputSpectrumIterator& last,
                                          MSExperiment<OutputPeakType>& ms_exp)
  {
    Int counter = 0;
    // go through the clusters
    for (std::multimap<DoubleReal, IsotopeCluster>::iterator it = iso_map_.begin();
         it != iso_map_.end();
         ++it)
    {
#ifdef DEBUG_2D
      std::cout << "element: " << counter << std::endl;
      std::cout << "mz: " << it->first << std::endl << "rts: ";
//              for(Size i=0;i<it->second.scans.size();++i) std::cout << it->second.scans[i] << "\n";
      std::cout << std::endl << "peaks: ";
      IsotopeCluster::IndexSet::const_iterator iter = it->second.peaks.begin();
      for (; iter != it->second.peaks.end(); ++iter)
        std::cout << ms_exp[iter->first].getRT() << " " << (ms_exp[iter->first][iter->second]).getMZ() << std::endl;

//for(Size i=0;i<it->second.peaks.size();++i) std::cout << ms_exp[it->first].getRT() << " "<<(ms_exp[it->first][it->second]).getMZ()<<std::endl;
      std::cout << std::endl << std::endl;

#endif

      // prepare for optimization:
      // determine the matching peaks
      matching_peaks_.clear();
      findMatchingPeaks_(it, ms_exp);
      TwoDOptimization::Data d;
      d.penalties = penalties_;
      d.matching_peaks = matching_peaks_;
      // and the endpoints of each isotope pattern in the cluster
      getRegionEndpoints_(ms_exp, first, last, counter, 400, d);

      // peaks have to be stored globally
      d.iso_map_iter = it;

      d.picked_peaks = ms_exp;
      d.raw_data_first =  first;

      Size nr_diff_peaks = matching_peaks_.size();
      d.total_nr_peaks = it->second.peaks.size();

      Size nr_parameters = nr_diff_peaks * 3 + d.total_nr_peaks;

      gsl_vector* start_value = gsl_vector_alloc(nr_parameters);
      gsl_vector_set_zero(start_value);

      // initialize parameters for optimization
      std::map<Int, std::vector<PeakIndex> >::iterator m_peaks_it = d.matching_peaks.begin();
      DoubleReal av_mz = 0, av_lw = 0, av_rw = 0, avr_height = 0, height;
      Int peak_counter = 0;
      Int diff_peak_counter = 0;
      // go through the matching peaks
      for (; m_peaks_it != d.matching_peaks.end(); ++m_peaks_it)
      {
        av_mz = 0, av_lw = 0, av_rw = 0, avr_height = 0;
        std::vector<PeakIndex>::iterator iter_iter = (m_peaks_it)->second.begin();
        for (; iter_iter != m_peaks_it->second.end(); ++iter_iter)
        {
          height = ms_exp[(iter_iter)->spectrum].getFloatDataArrays()[1][(iter_iter)->peak]; //(iter_iter)->getPeak(ms_exp).getIntensity();
          avr_height += height;
          av_mz += (iter_iter)->getPeak(ms_exp).getMZ() * height;
          av_lw += ms_exp[(iter_iter)->spectrum].getFloatDataArrays()[3][(iter_iter)->peak] * height; //left width
          av_rw +=    ms_exp[(iter_iter)->spectrum].getFloatDataArrays()[4][(iter_iter)->peak] * height; //right width
          gsl_vector_set(start_value, peak_counter, height);
          ++peak_counter;
        }
        gsl_vector_set(start_value, d.total_nr_peaks + 3 * diff_peak_counter, av_mz / avr_height);
        gsl_vector_set(start_value, d.total_nr_peaks + 3 * diff_peak_counter + 1, av_lw / avr_height);
        gsl_vector_set(start_value, d.total_nr_peaks + 3 * diff_peak_counter + 2, av_rw / avr_height);
        ++diff_peak_counter;
      }

#ifdef DEBUG_2D
      std::cout << "----------------------------\n\nstart_value: " << std::endl;
      for (Size k = 0; k < start_value->size; ++k)
      {
        std::cout << gsl_vector_get(start_value, k) << std::endl;
      }
#endif
      Int num_positions = 0;
      for (Size i = 0; i < d.signal2D.size(); i += 2)
      {
        num_positions += (d.signal2D[i + 1].second - d.signal2D[i].second + 1);
#ifdef DEBUG_2D
        std::cout << d.signal2D[i + 1].second << " - " << d.signal2D[i].second << " +1 " << std::endl;
#endif

      }
#ifdef DEBUG_2D
      std::cout << "num_positions : " << num_positions << std::endl;
#endif
      // The gsl algorithms require us to provide function pointers for the evaluation of
      // the target function.
      gsl_multifit_function_fdf fit_function;
      fit_function.f   = (Int (*)(const gsl_vector* x, void* params, gsl_vector* f)) & OpenMS::TwoDOptimization::residual2D_;
      fit_function.df  = (Int (*)(const gsl_vector* x, void* params, gsl_matrix* J)) & OpenMS::TwoDOptimization::jacobian2D_;
      fit_function.fdf = (Int (*)(const gsl_vector* x, void* params, gsl_vector* f, gsl_matrix* J)) & OpenMS::TwoDOptimization::evaluate2D_;
      // gsl crashes when n is smaller than p!
      fit_function.n   = std::max(num_positions + 1, (Int)(nr_parameters));
      fit_function.p   = nr_parameters;
      fit_function.params = &d;
#ifdef DEBUG_2D
      std::cout << "fit_function.n " << fit_function.n
                << "\tfit_function.p " << fit_function.p << std::endl;
#endif
      const gsl_multifit_fdfsolver_type* type = gsl_multifit_fdfsolver_lmsder;

      gsl_multifit_fdfsolver* fit = gsl_multifit_fdfsolver_alloc(type,
                                                                 std::max(num_positions + 1, (Int)(nr_parameters)),
                                                                 nr_parameters);

      gsl_multifit_fdfsolver_set(fit, &fit_function, start_value);



      // initial norm
#ifdef DEBUG_2D
      std::cout << "Before optimization: ||f|| = " << gsl_blas_dnrm2(fit->f) << std::endl;
#endif
      // Iteration
      UInt iteration = 0;
      Int status;

      do
      {
        iteration++;
        status = gsl_multifit_fdfsolver_iterate(fit);
#ifdef DEBUG_2D
        std::cout << "Iteration " << iteration << "; Status " << gsl_strerror(status) << "; " << std::endl;
        std::cout << "||f|| = " << gsl_blas_dnrm2(fit->f) << std::endl;
        std::cout << "Number of parms: " << nr_parameters << std::endl;
        std::cout << "Delta: " << gsl_blas_dnrm2(fit->dx) << std::endl;
#endif

        status = gsl_multifit_test_delta(fit->dx, fit->x, eps_abs_, eps_rel_);
        if (status != GSL_CONTINUE)
          break;

      }
      while (status == GSL_CONTINUE && iteration < max_iteration_);

#ifdef DEBUG_2D
      std::cout << "Finished! No. of iterations" << iteration << std::endl;
      std::cout << "Delta: " << gsl_blas_dnrm2(fit->dx) << std::endl;
      DoubleReal chi = gsl_blas_dnrm2(fit->f);
      std::cout << "After optimization: || f || = " << gsl_blas_dnrm2(fit->f) << std::endl;
      std::cout << "chisq/dof = " << pow(chi, 2.0) / (num_positions - nr_parameters);


      std::cout << "----------------------------------------------\n\nnachher" << std::endl;
      for (Size k = 0; k < fit->x->size; ++k)
      {
        std::cout << gsl_vector_get(fit->x, k) << std::endl;
      }
#endif
      Int peak_idx = 0;
      std::map<Int, std::vector<PeakIndex> >::iterator itv
        = d.matching_peaks.begin();
      for (; itv != d.matching_peaks.end(); ++itv)
      {
        Int i = distance(d.matching_peaks.begin(), itv);
        for (Size j = 0; j < itv->second.size(); ++j)
        {

#ifdef DEBUG_2D
          std::cout << "pos: " << itv->second[j].getPeak(ms_exp).getMZ() << "\nint: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[1][itv->second[j].peak] //itv->second[j].getPeak(ms_exp).getIntensity()
                    << "\nlw: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[3][itv->second[j].peak]
                    << "\nrw: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[4][itv->second[j].peak] << "\n";

#endif
          DoubleReal mz = gsl_vector_get(fit->x, d.total_nr_peaks + 3 * i);
          ms_exp[itv->second[j].spectrum][itv->second[j].peak].setMZ(mz);
          DoubleReal height = (gsl_vector_get(fit->x, peak_idx));
          ms_exp[itv->second[j].spectrum].getFloatDataArrays()[1][itv->second[j].peak] = height;
          DoubleReal left_width = gsl_vector_get(fit->x, d.total_nr_peaks + 3 * i + 1);
          ms_exp[itv->second[j].spectrum].getFloatDataArrays()[3][itv->second[j].peak] = left_width;
          DoubleReal right_width = gsl_vector_get(fit->x, d.total_nr_peaks + 3 * i + 2);
          ms_exp[itv->second[j].spectrum].getFloatDataArrays()[4][itv->second[j].peak] = right_width;
          // calculate area
          if ((PeakShape::Type)(Int)ms_exp[itv->second[j].spectrum].getFloatDataArrays()[5][itv->second[j].peak] == PeakShape::LORENTZ_PEAK)
          {
            DoubleReal x_left_endpoint = mz - 1 / left_width* sqrt(height / 1 - 1);
            DoubleReal x_rigth_endpoint = mz + 1 / right_width* sqrt(height / 1 - 1);
            DoubleReal area_left = -height / left_width* atan(left_width * (x_left_endpoint - mz));
            DoubleReal area_right = -height / right_width* atan(right_width * (mz - x_rigth_endpoint));
            ms_exp[itv->second[j].spectrum][itv->second[j].peak].setIntensity(area_left + area_right);
          }
          else         // it's a sech peak
          {
            DoubleReal x_left_endpoint = mz - 1 / left_width* boost::math::acosh(sqrt(height / 0.001));
            DoubleReal x_rigth_endpoint = mz + 1 / right_width* boost::math::acosh(sqrt(height / 0.001));
            DoubleReal area_left = -height / left_width * (sinh(left_width * (mz - x_left_endpoint)) / cosh(left_width * (mz - x_left_endpoint)));
            DoubleReal area_right = -height / right_width * (sinh(right_width * (mz - x_rigth_endpoint)) / cosh(right_width * (mz - x_rigth_endpoint)));
            ms_exp[itv->second[j].spectrum][itv->second[j].peak].setIntensity(area_left + area_right);
          }


#ifdef DEBUG_2D
          std::cout << "pos: " << itv->second[j].getPeak(ms_exp).getMZ() << "\nint: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[1][itv->second[j].peak] //itv->second[j].getPeak(ms_exp).getIntensity()
                    << "\nlw: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[3][itv->second[j].peak]
                    << "\nrw: " << itv->second[j].getSpectrum(ms_exp).getFloatDataArrays()[4][itv->second[j].peak] << "\n";

//                              std::cout << "pos: "<<itv->second[j]->getMZ()<<"\nint: "<<itv->second[j]->getIntensity()
//                                                  <<"\nlw: "<<itv->second[j]->getLeftWidthParameter()
//                                                  <<"\nrw: "<<itv->second[j]->getRightWidthParameter() << "\n";

#endif

          ++peak_idx;


        }
      }

      gsl_multifit_fdfsolver_free(fit);
      gsl_vector_free(start_value);
      ++counter;
    } // end for
    //#undef DEBUG_2D
  }

  template <typename InputSpectrumIterator, typename OutputPeakType>
  void TwoDOptimization::optimizeRegionsScanwise_(InputSpectrumIterator& first,
                                                  InputSpectrumIterator& last,
                                                  MSExperiment<OutputPeakType>& ms_exp)
  {
    Int counter = 0;
    TwoDOptimization::Data d;
    d.picked_peaks = ms_exp;
    d.raw_data_first =  first;

    //std::cout << "richtig hier" << std::endl;
    struct OpenMS::OptimizationFunctions::PenaltyFactors penalties;


    DataValue dv = param_.getValue("penalties:position");
    if (dv.isEmpty() || dv.toString() == "")
      penalties.pos = 0.;
    else
      penalties.pos = (float)dv;

    dv = param_.getValue("penalties:left_width");
    if (dv.isEmpty() || dv.toString() == "")
      penalties.lWidth = 1.;
    else
      penalties.lWidth = (float)dv;

    dv = param_.getValue("penalties:right_width");
    if (dv.isEmpty() || dv.toString() == "")
      penalties.rWidth = 1.;
    else
      penalties.rWidth = (float)dv;
#ifdef DEBUG_2D
    std::cout << penalties.pos << " "
              << penalties.rWidth << " "
              << penalties.lWidth << std::endl;
#endif
//      MSExperiment<Peak1D >::const_iterator help = first;
//      // std::cout << "\n\n\n\n---------------------------------------------------------------";
//      while(help!=last)
//          {
//              // std::cout<<help->getRT()<<std::endl;
//              ++help;
//          }
    // std::cout << "---------------------------------------------------------------\n\n\n\n";

    UInt max_iteration;
    dv = param_.getValue("iterations");
    if (dv.isEmpty() || dv.toString() == "")
      max_iteration = 15;
    else
      max_iteration = (UInt)dv;

    DoubleReal eps_abs;
    dv = param_.getValue("delta_abs_error");
    if (dv.isEmpty() || dv.toString() == "")
      eps_abs = 1e-04f;
    else
      eps_abs = (DoubleReal)dv;

    DoubleReal eps_rel;
    dv = param_.getValue("delta_rel_error");
    if (dv.isEmpty() || dv.toString() == "")
      eps_rel = 1e-04f;
    else
      eps_rel = (DoubleReal)dv;

    std::vector<PeakShape> peak_shapes;


    // go through the clusters
    for (std::multimap<DoubleReal, IsotopeCluster>::iterator it = iso_map_.begin();
         it != iso_map_.end();
         ++it)
    {
      d.iso_map_iter = it;
#ifdef DEBUG_2D
      std::cerr << "element: " << counter << std::endl;
      std::cerr << "mz: " << it->first << std::endl << "rts: ";
      for (Size i = 0; i < it->second.scans.size(); ++i)
        std::cerr << it->second.scans[i] << "\n";
      std::cerr << std::endl << "peaks: ";
      IsotopeCluster::IndexSet::const_iterator iter = it->second.peaks.begin();
      for (; iter != it->second.peaks.end(); ++iter)
        std::cerr << ms_exp[iter->first].getRT() << " " << (ms_exp[iter->first][iter->second]).getMZ() << std::endl;
      //for(Size i=0;i<it->second.peaks_.size();++i) std::cout << ms_exp[it->first].getRT() << " "<<(ms_exp[it->first][it->second]).getMZ()<<std::endl;
      std::cerr << std::endl << std::endl;

#endif
      // prepare for optimization:
      // determine the matching peaks
      // and the endpoints of each isotope pattern in the cluster

      getRegionEndpoints_(ms_exp, first, last, counter, 400, d);
      OptimizePick::Data data;


      Size idx = 0;
      for (Size i = 0; i < d.signal2D.size() / 2; ++i)
      {
        data.positions.clear();
        data.signal.clear();

        MSExperiment<Peak1D>::SpectrumType::const_iterator ms_it =
          (d.raw_data_first + d.signal2D[2 * i].first)->begin() + d.signal2D[2 * i].second;
        Int size = distance(ms_it, (d.raw_data_first + d.signal2D[2 * i].first)->begin() + d.signal2D[2 * i + 1].second);
        data.positions.reserve(size);
        data.signal.reserve(size);

        while (ms_it != (d.raw_data_first + d.signal2D[2 * i].first)->begin() + d.signal2D[2 * i + 1].second)
        {
          data.positions.push_back(ms_it->getMZ());
          data.signal.push_back(ms_it->getIntensity());
          ++ms_it;
        }


        IsotopeCluster::IndexPair pair;
        pair.first =  d.iso_map_iter->second.peaks.begin()->first + idx;

        IsotopeCluster::IndexSet::const_iterator set_iter = lower_bound(d.iso_map_iter->second.peaks.begin(),
                                                                        d.iso_map_iter->second.peaks.end(),
                                                                        pair, PairComparatorFirstElement<IsotopeCluster::IndexPair>());


        // find the last entry with this rt-value
        ++pair.first;
        IsotopeCluster::IndexSet::const_iterator set_iter2 = lower_bound(d.iso_map_iter->second.peaks.begin(),
                                                                         d.iso_map_iter->second.peaks.end(),
                                                                         pair, PairComparatorFirstElement<IsotopeCluster::IndexPair>());

        while (set_iter != set_iter2)
        {
          const Size peak_index = set_iter->second;
          const MSSpectrum<>& spec = ms_exp[set_iter->first];
          PeakShape shape(spec.getFloatDataArrays()[1][peak_index], //intensity
                          spec[peak_index].getMZ(),
                          spec.getFloatDataArrays()[3][peak_index], //left width
                          spec.getFloatDataArrays()[4][peak_index], //right width
                          spec[peak_index].getIntensity(), //area is stored in peak intensity
                          std::vector<Peak1D>::iterator(),
                          std::vector<Peak1D>::iterator(),
                          PeakShape::Type(Int(spec.getFloatDataArrays()[5][peak_index]))); //shape
          peak_shapes.push_back(shape);
          ++set_iter;
        }
#ifdef DEBUG_2D
        std::cout << "rt "
                  << (d.raw_data_first + d.signal2D[2 * i].first)->getRT()
                  << "\n";
#endif
        OptimizePick opt(penalties, max_iteration, eps_abs, eps_rel);
#ifdef DEBUG_2D
        std::cout << "vorher\n";

        for (Size p = 0; p < peak_shapes.size(); ++p)
        {
          std::cout << peak_shapes[p].mz_position << "\t" << peak_shapes[p].height
                    << "\t" << peak_shapes[p].left_width << "\t" << peak_shapes[p].right_width  << std::endl;
        }
#endif
        opt.optimize(peak_shapes, data);
#ifdef DEBUG_2D
        std::cout << "nachher\n";
        for (Size p = 0; p < peak_shapes.size(); ++p)
        {
          std::cout << peak_shapes[p].mz_position << "\t" << peak_shapes[p].height
                    << "\t" << peak_shapes[p].left_width << "\t" << peak_shapes[p].right_width  << std::endl;
        }
#endif
        std::sort(peak_shapes.begin(), peak_shapes.end(), PeakShape::PositionLess());
        pair.first =  d.iso_map_iter->second.peaks.begin()->first + idx;

        set_iter = lower_bound(d.iso_map_iter->second.peaks.begin(),
                               d.iso_map_iter->second.peaks.end(),
                               pair, PairComparatorFirstElement<IsotopeCluster::IndexPair>());
        Size p = 0;
        while (p < peak_shapes.size())
        {
          MSSpectrum<>& spec = ms_exp[set_iter->first];
          spec[set_iter->second].setMZ(peak_shapes[p].mz_position);
          spec.getFloatDataArrays()[3][set_iter->second] = peak_shapes[p].left_width;
          spec.getFloatDataArrays()[4][set_iter->second] = peak_shapes[p].right_width;
          spec.getFloatDataArrays()[1][set_iter->second] = peak_shapes[p].height; // maximum intensity
          // calculate area
          if (peak_shapes[p].type == PeakShape::LORENTZ_PEAK)
          {
            PeakShape& ps = peak_shapes[p];
            double x_left_endpoint = ps.mz_position - 1 / ps.left_width* sqrt(ps.height / 1 - 1);
            double x_rigth_endpoint = ps.mz_position + 1 / ps.right_width* sqrt(ps.height / 1 - 1);
            double area_left = -ps.height / ps.left_width* atan(ps.left_width * (x_left_endpoint - ps.mz_position));
            double area_right = -ps.height / ps.right_width* atan(ps.right_width * (ps.mz_position - x_rigth_endpoint));
            spec[set_iter->second].setIntensity(area_left + area_right); // area is stored as peak intensity
          }
          else        //It's a Sech - Peak
          {
            PeakShape& ps = peak_shapes[p];
            double x_left_endpoint = ps.mz_position - 1 / ps.left_width* boost::math::acosh(sqrt(ps.height / 0.001));
            double x_rigth_endpoint = ps.mz_position + 1 / ps.right_width* boost::math::acosh(sqrt(ps.height / 0.001));
            double area_left = ps.height / ps.left_width * (sinh(ps.left_width * (ps.mz_position - x_left_endpoint)) / cosh(ps.left_width * (ps.mz_position - x_left_endpoint)));
            double area_right = -ps.height / ps.right_width * (sinh(ps.right_width * (ps.mz_position - x_rigth_endpoint)) / cosh(ps.right_width * (ps.mz_position - x_rigth_endpoint)));
            spec[set_iter->second].setIntensity(area_left + area_right); // area is stored as peak intensity
          }
          ++set_iter;
          ++p;
        }
        ++idx;
        peak_shapes.clear();
      }

      ++counter;
    }
  }

  template <typename InputSpectrumIterator, typename OutputPeakType>
  void TwoDOptimization::getRegionEndpoints_(MSExperiment<OutputPeakType>& exp,
                                             InputSpectrumIterator& first,
                                             InputSpectrumIterator& last,
                                             Size iso_map_idx,
                                             DoubleReal noise_level,
                                             TwoDOptimization::Data& d)
  {
    d.signal2D.clear();
    typedef typename InputSpectrumIterator::value_type InputExperimentType;
    typedef typename InputExperimentType::value_type InputPeakType;
    typedef std::multimap<DoubleReal, IsotopeCluster> MapType;

    DoubleReal rt, first_peak_mz, last_peak_mz;

    //MSSpectrum<InputPeakType> spec;
    typename MSExperiment<InputPeakType>::SpectrumType spec;
    InputPeakType peak;

    MapType::iterator iso_map_iter = iso_map_.begin();
    for (Size i = 0; i < iso_map_idx; ++i)
      ++iso_map_iter;

#ifdef DEBUG2D
    std::cout << "rt begin: " << exp[iso_map_iter->second.scans[0]].getRT()
              << "\trt end: " << exp[iso_map_iter->second.scans[iso_map_iter->second.scans.size() - 1]].getRT()
              << " \t" << iso_map_iter->second.scans.size() << " scans"
              << std::endl;
#endif

    // get left and right endpoint for all scans in the current cluster
    for (Size i = 0; i < iso_map_iter->second.scans.size(); ++i)
    {
      typename MSExperiment<OutputPeakType>::iterator exp_it;

      // first the right scan through binary search
      rt = exp[iso_map_iter->second.scans[i]].getRT();
      spec.setRT(rt);
      InputSpectrumIterator iter = lower_bound(first, last, spec, typename MSSpectrum<InputPeakType>::RTLess());
      //  if(iter->getRT() != rt) --iter;
      exp_it = exp.RTBegin(rt);
#ifdef DEBUG2D
      std::cout << exp_it->getRT() << " vs " << iter->getRT() << std::endl;
#endif
      // now the right mz
      IsotopeCluster::IndexPair pair;
      pair.first =  iso_map_iter->second.peaks.begin()->first + i;
      // get iterator in peaks-set that points to the first peak in the current scan
      IsotopeCluster::IndexSet::const_iterator set_iter = lower_bound(iso_map_iter->second.peaks.begin(),
                                                                      iso_map_iter->second.peaks.end(),
                                                                      pair, PairComparatorFirstElement<IsotopeCluster::IndexPair>());

      // consider a bit more of the signal to the left
      first_peak_mz = (exp_it->begin() + set_iter->second)->getMZ() - 1;

      // find the last entry with this rt-value
      ++pair.first;
      IsotopeCluster::IndexSet::const_iterator set_iter2 = lower_bound(iso_map_iter->second.peaks.begin(),
                                                                       iso_map_iter->second.peaks.end(),
                                                                       pair, PairComparatorFirstElement<IsotopeCluster::IndexPair>());

      if (i == iso_map_iter->second.scans.size() - 1)
      {
        set_iter2 = iso_map_iter->second.peaks.end();
        --set_iter2;
      }
      else if (set_iter2 != iso_map_iter->second.peaks.begin())
        --set_iter2;

      last_peak_mz = (exp_it->begin() + set_iter2->second)->getMZ() + 1;

      //std::cout << rt<<": first peak mz "<<first_peak_mz << "\tlast peak mz "<<last_peak_mz <<std::endl;
      peak.setPosition(first_peak_mz);
      typename MSExperiment<InputPeakType>::SpectrumType::const_iterator raw_data_iter
        = lower_bound(iter->begin(), iter->end(), peak, typename InputPeakType::PositionLess());
      if (raw_data_iter != iter->begin())
      {
        --raw_data_iter;
      }
      DoubleReal intensity = raw_data_iter->getIntensity();
      // while the intensity is falling go to the left
      while (raw_data_iter != iter->begin() && (raw_data_iter - 1)->getIntensity() < intensity &&
             (raw_data_iter - 1)->getIntensity() > noise_level)
      {
        --raw_data_iter;
        intensity = raw_data_iter->getIntensity();
      }
      ++raw_data_iter;
      IsotopeCluster::IndexPair left, right;
      left.first = distance(first, iter);
      left.second = raw_data_iter - iter->begin();
#ifdef DEBUG2D
      std::cout << "left: " << iter->getRT() << "\t" << raw_data_iter->getMZ() << std::endl;
#endif
      // consider a bit more of the signal to the right
      peak.setPosition(last_peak_mz + 1);
      raw_data_iter
        = upper_bound(iter->begin(), iter->end(), peak, typename InputPeakType::PositionLess());
      if (raw_data_iter == iter->end())
        --raw_data_iter;
      intensity = raw_data_iter->getIntensity();
      // while the intensity is falling go to the right
      while (raw_data_iter + 1 != iter->end() && (raw_data_iter + 1)->getIntensity() < intensity)
      {
        ++raw_data_iter;
        intensity = raw_data_iter->getIntensity();
        if ((raw_data_iter + 1 != iter->end()) && (raw_data_iter + 1)->getIntensity() > noise_level)
          break;
      }
      right.first = left.first;
      right.second = raw_data_iter - iter->begin();
#ifdef DEBUG2D
      std::cout << "right: " << iter->getRT() << "\t" << raw_data_iter->getMZ() << std::endl;
#endif
      // region endpoints are stored in global vector
      d.signal2D.push_back(left);
      d.signal2D.push_back(right);
    }
#ifdef DEBUG2D
    //std::cout << "fertig"<< std::endl;
    std::cout << first_peak_mz << "\t" << last_peak_mz << std::endl;
#endif
  }

}

#endif //OPENMS_TRANSFORMATIONS_RAW2PEAK_TWODOPTIMIZATION_H