// $Id:
//
// FORESTER -- software libraries and applications
// for evolutionary biology research and applications.
//
// Copyright (C) 2008-2009 Christian M. Zmasek
// Copyright (C) 2008-2009 Burnham Institute for Medical Research
// All rights reserved
//
// This library is free software; you can redistribute it and/or
// modify it under the terms of the GNU Lesser General Public
// License as published by the Free Software Foundation; either
// version 2.1 of the License, or (at your option) any later version.
//
// This library is distributed in the hope that it will be useful,
// but WITHOUT ANY WARRANTY; without even the implied warranty of
// MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU
// Lesser General Public License for more details.
//
// You should have received a copy of the GNU Lesser General Public
// License along with this library; if not, write to the Free Software
// Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA
//
// Contact: phylosoft @ gmail . com
// WWW: https://sites.google.com/site/cmzmasek/home/software/forester

package org.forester.surfacing;

import java.awt.Color;
import java.io.BufferedWriter;
import java.io.File;
import java.io.FileWriter;
import java.io.IOException;
import java.io.Writer;
import java.text.DecimalFormat;
import java.text.NumberFormat;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.Collections;
import java.util.Comparator;
import java.util.HashMap;
import java.util.HashSet;
import java.util.Iterator;
import java.util.List;
import java.util.Map;
import java.util.Map.Entry;
import java.util.PriorityQueue;
import java.util.Set;
import java.util.SortedMap;
import java.util.SortedSet;
import java.util.TreeMap;
import java.util.TreeSet;
import java.util.regex.Matcher;
import java.util.regex.Pattern;

import org.forester.application.surfacing;
import org.forester.evoinference.distance.NeighborJoining;
import org.forester.evoinference.matrix.character.BasicCharacterStateMatrix;
import org.forester.evoinference.matrix.character.CharacterStateMatrix;
import org.forester.evoinference.matrix.character.CharacterStateMatrix.BinaryStates;
import org.forester.evoinference.matrix.character.CharacterStateMatrix.Format;
import org.forester.evoinference.matrix.character.CharacterStateMatrix.GainLossStates;
import org.forester.evoinference.matrix.distance.DistanceMatrix;
import org.forester.go.GoId;
import org.forester.go.GoNameSpace;
import org.forester.go.GoTerm;
import org.forester.go.PfamToGoMapping;
import org.forester.io.parsers.nexus.NexusConstants;
import org.forester.io.parsers.phyloxml.PhyloXmlUtil;
import org.forester.io.parsers.util.ParserUtils;
import org.forester.io.writers.PhylogenyWriter;
import org.forester.phylogeny.Phylogeny;
import org.forester.phylogeny.PhylogenyMethods;
import org.forester.phylogeny.PhylogenyNode;
import org.forester.phylogeny.PhylogenyNode.NH_CONVERSION_SUPPORT_VALUE_STYLE;
import org.forester.phylogeny.data.BinaryCharacters;
import org.forester.phylogeny.data.Confidence;
import org.forester.phylogeny.data.Taxonomy;
import org.forester.phylogeny.factories.ParserBasedPhylogenyFactory;
import org.forester.phylogeny.iterators.PhylogenyNodeIterator;
import org.forester.protein.BasicDomain;
import org.forester.protein.BasicProtein;
import org.forester.protein.BinaryDomainCombination;
import org.forester.protein.Domain;
import org.forester.protein.Protein;
import org.forester.species.Species;
import org.forester.surfacing.DomainSimilarity.PRINT_OPTION;
import org.forester.surfacing.DomainSimilarityCalculator.Detailedness;
import org.forester.surfacing.GenomeWideCombinableDomains.GenomeWideCombinableDomainsSortOrder;
import org.forester.util.AsciiHistogram;
import org.forester.util.BasicDescriptiveStatistics;
import org.forester.util.BasicTable;
import org.forester.util.BasicTableParser;
import org.forester.util.CommandLineArguments;
import org.forester.util.DescriptiveStatistics;
import org.forester.util.ForesterUtil;
import org.forester.util.TaxonomyColors;
import org.forester.util.TaxonomyGroups;

public final class SurfacingUtil {

    public final static Pattern              PATTERN_SP_STYLE_TAXONOMY        = Pattern.compile( "^[A-Z0-9]{3,5}$" );
    private final static Map<String, String> _TAXCODE_HEXCOLORSTRING_MAP      = new HashMap<String, String>();
    private final static Map<String, String> _TAXCODE_TAXGROUP_MAP            = new HashMap<String, String>();
    private static final Comparator<Domain>  ASCENDING_CONFIDENCE_VALUE_ORDER = new Comparator<Domain>() {

                                                                                  @Override
                                                                                  public int compare( final Domain d1,
                                                                                                      final Domain d2 ) {
                                                                                      if ( d1.getPerDomainEvalue() < d2
                                                                                              .getPerDomainEvalue() ) {
                                                                                          return -1;
                                                                                      }
                                                                                      else if ( d1
                                                                                              .getPerDomainEvalue() > d2
                                                                                                      .getPerDomainEvalue() ) {
                                                                                          return 1;
                                                                                      }
                                                                                      else {
                                                                                          return d1.compareTo( d2 );
                                                                                      }
                                                                                  }
                                                                              };
    private final static NumberFormat        FORMATTER_3                      = new DecimalFormat( "0.000" );

    private SurfacingUtil() {
        // Hidden constructor.
    }

    public static void addAllBinaryDomainCombinationToSet( final GenomeWideCombinableDomains genome,
                                                           final SortedSet<BinaryDomainCombination> binary_domain_combinations ) {
        final SortedMap<String, CombinableDomains> all_cd = genome.getAllCombinableDomainsIds();
        for( final String domain_id : all_cd.keySet() ) {
            binary_domain_combinations.addAll( all_cd.get( domain_id ).toBinaryDomainCombinations() );
        }
    }

    public static void addAllDomainIdsToSet( final GenomeWideCombinableDomains genome,
                                             final SortedSet<String> domain_ids ) {
        final SortedSet<String> domains = genome.getAllDomainIds();
        for( final String domain : domains ) {
            domain_ids.add( domain );
        }
    }

    public static DescriptiveStatistics calculateDescriptiveStatisticsForMeanValues( final Set<DomainSimilarity> similarities ) {
        final DescriptiveStatistics stats = new BasicDescriptiveStatistics();
        for( final DomainSimilarity similarity : similarities ) {
            stats.addValue( similarity.getMeanSimilarityScore() );
        }
        return stats;
    }

    public static void checkForOutputFileWriteability( final File outfile ) {
        final String error = ForesterUtil.isWritableFile( outfile );
        if ( !ForesterUtil.isEmpty( error ) ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, error );
        }
    }

    public static void checkWriteabilityForPairwiseComparisons( final DomainSimilarity.PRINT_OPTION domain_similarity_print_option,
                                                                final String[][] input_file_properties,
                                                                final String automated_pairwise_comparison_suffix,
                                                                final File outdir ) {
        for( int i = 0; i < input_file_properties.length; ++i ) {
            for( int j = 0; j < i; ++j ) {
                final String species_i = input_file_properties[ i ][ 1 ];
                final String species_j = input_file_properties[ j ][ 1 ];
                String pairwise_similarities_output_file_str = surfacing.PAIRWISE_DOMAIN_COMPARISONS_PREFIX + species_i
                        + "_" + species_j + automated_pairwise_comparison_suffix;
                switch ( domain_similarity_print_option ) {
                    case HTML:
                        if ( !pairwise_similarities_output_file_str.endsWith( ".html" ) ) {
                            pairwise_similarities_output_file_str += ".html";
                        }
                        break;
                }
                final String error = ForesterUtil
                        .isWritableFile( new File( outdir == null ? pairwise_similarities_output_file_str
                                : outdir + ForesterUtil.FILE_SEPARATOR + pairwise_similarities_output_file_str ) );
                if ( !ForesterUtil.isEmpty( error ) ) {
                    ForesterUtil.fatalError( surfacing.PRG_NAME, error );
                }
            }
        }
    }

    public static void collectChangedDomainCombinationsFromBinaryStatesMatrixAsListToFile( final CharacterStateMatrix<CharacterStateMatrix.GainLossStates> matrix,
                                                                                           final BinaryDomainCombination.DomainCombinationType dc_type,
                                                                                           final List<BinaryDomainCombination> all_binary_domains_combination_gained,
                                                                                           final boolean get_gains ) {
        final SortedSet<String> sorted_ids = new TreeSet<String>();
        for( int i = 0; i < matrix.getNumberOfIdentifiers(); ++i ) {
            sorted_ids.add( matrix.getIdentifier( i ) );
        }
        for( final String id : sorted_ids ) {
            for( int c = 0; c < matrix.getNumberOfCharacters(); ++c ) {
                if ( ( get_gains && ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.GAIN ) )
                        || ( !get_gains
                                && ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.LOSS ) ) ) {
                    if ( dc_type == BinaryDomainCombination.DomainCombinationType.DIRECTED_ADJACTANT ) {
                        all_binary_domains_combination_gained.add( AdjactantDirectedBinaryDomainCombination
                                .obtainInstance( matrix.getCharacter( c ) ) );
                    }
                    else if ( dc_type == BinaryDomainCombination.DomainCombinationType.DIRECTED ) {
                        all_binary_domains_combination_gained
                                .add( DirectedBinaryDomainCombination.obtainInstance( matrix.getCharacter( c ) ) );
                    }
                    else {
                        all_binary_domains_combination_gained
                                .add( BasicBinaryDomainCombination.obtainInstance( matrix.getCharacter( c ) ) );
                    }
                }
            }
        }
    }

    public static Map<String, List<GoId>> createDomainIdToGoIdMap( final List<PfamToGoMapping> pfam_to_go_mappings ) {
        final Map<String, List<GoId>> domain_id_to_go_ids_map = new HashMap<String, List<GoId>>( pfam_to_go_mappings
                .size() );
        for( final PfamToGoMapping pfam_to_go : pfam_to_go_mappings ) {
            if ( !domain_id_to_go_ids_map.containsKey( pfam_to_go.getKey() ) ) {
                domain_id_to_go_ids_map.put( pfam_to_go.getKey(), new ArrayList<GoId>() );
            }
            domain_id_to_go_ids_map.get( pfam_to_go.getKey() ).add( pfam_to_go.getValue() );
        }
        return domain_id_to_go_ids_map;
    }

    public static Map<String, Set<String>> createDomainIdToSecondaryFeaturesMap( final File secondary_features_map_file )
            throws IOException {
        final BasicTable<String> primary_table = BasicTableParser.parse( secondary_features_map_file, '\t' );
        final Map<String, Set<String>> map = new TreeMap<String, Set<String>>();
        for( int r = 0; r < primary_table.getNumberOfRows(); ++r ) {
            final String domain_id = primary_table.getValue( 0, r );
            if ( !map.containsKey( domain_id ) ) {
                map.put( domain_id, new HashSet<String>() );
            }
            map.get( domain_id ).add( primary_table.getValue( 1, r ) );
        }
        return map;
    }

    public static Phylogeny createNjTreeBasedOnMatrixToFile( final File nj_tree_outfile,
                                                             final DistanceMatrix distance ) {
        checkForOutputFileWriteability( nj_tree_outfile );
        final NeighborJoining nj = NeighborJoining.createInstance();
        final Phylogeny phylogeny = nj.execute( ( DistanceMatrix ) distance );
        phylogeny.setName( nj_tree_outfile.getName() );
        writePhylogenyToFile( phylogeny, nj_tree_outfile.toString() );
        return phylogeny;
    }

    public static StringBuilder createParametersAsString( final boolean ignore_dufs,
                                                          final double ie_value_max,
                                                          final double fs_e_value_max,
                                                          final int max_allowed_overlap,
                                                          final boolean no_engulfing_overlaps,
                                                          final File cutoff_scores_file,
                                                          final BinaryDomainCombination.DomainCombinationType dc_type ) {
        final StringBuilder parameters_sb = new StringBuilder();
        parameters_sb.append( "iE-value: " + ie_value_max );
        parameters_sb.append( ", FS E-value: " + fs_e_value_max );
        if ( cutoff_scores_file != null ) {
            parameters_sb.append( ", Cutoff-scores-file: " + cutoff_scores_file );
        }
        else {
            parameters_sb.append( ", Cutoff-scores-file: not-set" );
        }
        if ( max_allowed_overlap != surfacing.MAX_ALLOWED_OVERLAP_DEFAULT ) {
            parameters_sb.append( ", Max-overlap: " + max_allowed_overlap );
        }
        else {
            parameters_sb.append( ", Max-overlap: not-set" );
        }
        if ( no_engulfing_overlaps ) {
            parameters_sb.append( ", Engulfing-overlaps: not-allowed" );
        }
        else {
            parameters_sb.append( ", Engulfing-overlaps: allowed" );
        }
        if ( ignore_dufs ) {
            parameters_sb.append( ", Ignore-dufs: true" );
        }
        else {
            parameters_sb.append( ", Ignore-dufs: false" );
        }
        parameters_sb.append( ", DC type (if applicable): " + dc_type );
        return parameters_sb;
    }

    public static void createSplitWriters( final File out_dir,
                                           final String my_outfile,
                                           final Map<Character, Writer> split_writers )
            throws IOException {
        split_writers.put( 'a',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_A.html" ) ) );
        split_writers.put( 'b',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_B.html" ) ) );
        split_writers.put( 'c',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_C.html" ) ) );
        split_writers.put( 'd',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_D.html" ) ) );
        split_writers.put( 'e',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_E.html" ) ) );
        split_writers.put( 'f',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_F.html" ) ) );
        split_writers.put( 'g',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_G.html" ) ) );
        split_writers.put( 'h',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_H.html" ) ) );
        split_writers.put( 'i',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_I.html" ) ) );
        split_writers.put( 'j',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_J.html" ) ) );
        split_writers.put( 'k',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_K.html" ) ) );
        split_writers.put( 'l',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_L.html" ) ) );
        split_writers.put( 'm',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_M.html" ) ) );
        split_writers.put( 'n',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_N.html" ) ) );
        split_writers.put( 'o',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_O.html" ) ) );
        split_writers.put( 'p',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_P.html" ) ) );
        split_writers.put( 'q',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_Q.html" ) ) );
        split_writers.put( 'r',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_R.html" ) ) );
        split_writers.put( 's',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_S.html" ) ) );
        split_writers.put( 't',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_T.html" ) ) );
        split_writers.put( 'u',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_U.html" ) ) );
        split_writers.put( 'v',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_V.html" ) ) );
        split_writers.put( 'w',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_W.html" ) ) );
        split_writers.put( 'x',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_X.html" ) ) );
        split_writers.put( 'y',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_Y.html" ) ) );
        split_writers.put( 'z',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_Z.html" ) ) );
        split_writers.put( '0',
                           new BufferedWriter( new FileWriter( out_dir + ForesterUtil.FILE_SEPARATOR + my_outfile
                                   + "_domains_0.html" ) ) );
    }

    public static Map<String, Integer> createTaxCodeToIdMap( final Phylogeny phy ) {
        final Map<String, Integer> m = new HashMap<String, Integer>();
        for( final PhylogenyNodeIterator iter = phy.iteratorExternalForward(); iter.hasNext(); ) {
            final PhylogenyNode n = iter.next();
            if ( n.getNodeData().isHasTaxonomy() ) {
                final Taxonomy t = n.getNodeData().getTaxonomy();
                final String c = t.getTaxonomyCode();
                if ( !ForesterUtil.isEmpty( c ) ) {
                    if ( n.getNodeData().getTaxonomy() == null ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME, "no taxonomy id for node " + n );
                    }
                    final String id = n.getNodeData().getTaxonomy().getIdentifier().getValue();
                    if ( ForesterUtil.isEmpty( id ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME, "no taxonomy id for node " + n );
                    }
                    if ( m.containsKey( c ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME, "taxonomy code " + c + " is not unique" );
                    }
                    final int iid = Integer.valueOf( id );
                    if ( m.containsValue( iid ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME, "taxonomy id " + iid + " is not unique" );
                    }
                    m.put( c, iid );
                }
            }
            else {
                ForesterUtil.fatalError( surfacing.PRG_NAME, "no taxonomy for node " + n );
            }
        }
        return m;
    }

    public static void decoratePrintableDomainSimilarities( final SortedSet<DomainSimilarity> domain_similarities,
                                                            final Detailedness detailedness ) {
        for( final DomainSimilarity domain_similarity : domain_similarities ) {
            if ( domain_similarity instanceof DomainSimilarity ) {
                final DomainSimilarity printable_domain_similarity = domain_similarity;
                printable_domain_similarity.setDetailedness( detailedness );
            }
        }
    }

    public static void doit( final List<Protein> proteins,
                             final List<String> query_domain_ids_nc_order,
                             final Writer out,
                             final String separator,
                             final String limit_to_species,
                             final Map<String, List<Integer>> average_protein_lengths_by_dc )
            throws IOException {
        for( final Protein protein : proteins ) {
            if ( ForesterUtil.isEmpty( limit_to_species )
                    || protein.getSpecies().getSpeciesId().equalsIgnoreCase( limit_to_species ) ) {
                if ( protein.contains( query_domain_ids_nc_order, true ) ) {
                    out.write( protein.getSpecies().getSpeciesId() );
                    out.write( separator );
                    out.write( protein.getProteinId().getId() );
                    out.write( separator );
                    out.write( "[" );
                    final Set<String> visited_domain_ids = new HashSet<String>();
                    boolean first = true;
                    for( final Domain domain : protein.getProteinDomains() ) {
                        if ( !visited_domain_ids.contains( domain.getDomainId() ) ) {
                            visited_domain_ids.add( domain.getDomainId() );
                            if ( first ) {
                                first = false;
                            }
                            else {
                                out.write( " " );
                            }
                            out.write( domain.getDomainId() );
                            out.write( " {" );
                            out.write( "" + domain.getTotalCount() );
                            out.write( "}" );
                        }
                    }
                    out.write( "]" );
                    out.write( separator );
                    if ( !( ForesterUtil.isEmpty( protein.getDescription() )
                            || protein.getDescription().equals( SurfacingConstants.NONE ) ) ) {
                        out.write( protein.getDescription() );
                    }
                    out.write( separator );
                    if ( !( ForesterUtil.isEmpty( protein.getAccession() )
                            || protein.getAccession().equals( SurfacingConstants.NONE ) ) ) {
                        out.write( protein.getAccession() );
                    }
                    out.write( SurfacingConstants.NL );
                }
            }
        }
        out.flush();
    }

    public static void domainsPerProteinsStatistics( final String genome,
                                                     final List<Protein> protein_list,
                                                     final DescriptiveStatistics all_genomes_domains_per_potein_stats,
                                                     final SortedMap<Integer, Integer> all_genomes_domains_per_potein_histo,
                                                     final SortedSet<String> domains_which_are_always_single,
                                                     final SortedSet<String> domains_which_are_sometimes_single_sometimes_not,
                                                     final SortedSet<String> domains_which_never_single,
                                                     final Writer writer ) {
        final DescriptiveStatistics stats = new BasicDescriptiveStatistics();
        for( final Protein protein : protein_list ) {
            final int domains = protein.getNumberOfProteinDomains();
            //System.out.println( domains );
            stats.addValue( domains );
            all_genomes_domains_per_potein_stats.addValue( domains );
            if ( !all_genomes_domains_per_potein_histo.containsKey( domains ) ) {
                all_genomes_domains_per_potein_histo.put( domains, 1 );
            }
            else {
                all_genomes_domains_per_potein_histo.put( domains,
                                                          1 + all_genomes_domains_per_potein_histo.get( domains ) );
            }
            if ( domains == 1 ) {
                final String domain = protein.getProteinDomain( 0 ).getDomainId();
                if ( !domains_which_are_sometimes_single_sometimes_not.contains( domain ) ) {
                    if ( domains_which_never_single.contains( domain ) ) {
                        domains_which_never_single.remove( domain );
                        domains_which_are_sometimes_single_sometimes_not.add( domain );
                    }
                    else {
                        domains_which_are_always_single.add( domain );
                    }
                }
            }
            else if ( domains > 1 ) {
                for( final Domain d : protein.getProteinDomains() ) {
                    final String domain = d.getDomainId();
                    // System.out.println( domain );
                    if ( !domains_which_are_sometimes_single_sometimes_not.contains( domain ) ) {
                        if ( domains_which_are_always_single.contains( domain ) ) {
                            domains_which_are_always_single.remove( domain );
                            domains_which_are_sometimes_single_sometimes_not.add( domain );
                        }
                        else {
                            domains_which_never_single.add( domain );
                        }
                    }
                }
            }
        }
        try {
            writer.write( genome );
            writer.write( "\t" );
            if ( stats.getN() >= 1 ) {
                writer.write( stats.arithmeticMean() + "" );
                writer.write( "\t" );
                if ( stats.getN() >= 2 ) {
                    writer.write( stats.sampleStandardDeviation() + "" );
                }
                else {
                    writer.write( "" );
                }
                writer.write( "\t" );
                writer.write( stats.median() + "" );
                writer.write( "\t" );
                writer.write( stats.getN() + "" );
                writer.write( "\t" );
                writer.write( stats.getMin() + "" );
                writer.write( "\t" );
                writer.write( stats.getMax() + "" );
            }
            else {
                writer.write( "\t" );
                writer.write( "\t" );
                writer.write( "\t" );
                writer.write( "0" );
                writer.write( "\t" );
                writer.write( "\t" );
            }
            writer.write( "\n" );
        }
        catch ( final IOException e ) {
            e.printStackTrace();
        }
    }

    public static void executeDomainLengthAnalysis( final String[][] input_file_properties,
                                                    final int number_of_genomes,
                                                    final DomainLengthsTable domain_lengths_table,
                                                    final File outfile )
            throws IOException {
        final DecimalFormat df = new DecimalFormat( "#.00" );
        checkForOutputFileWriteability( outfile );
        final BufferedWriter out = new BufferedWriter( new FileWriter( outfile ) );
        out.write( "MEAN BASED STATISTICS PER SPECIES" );
        out.write( ForesterUtil.LINE_SEPARATOR );
        out.write( domain_lengths_table.createMeanBasedStatisticsPerSpeciesTable().toString() );
        out.write( ForesterUtil.LINE_SEPARATOR );
        out.write( ForesterUtil.LINE_SEPARATOR );
        final List<DomainLengths> domain_lengths_list = domain_lengths_table.getDomainLengthsList();
        out.write( "OUTLIER SPECIES PER DOMAIN (Z>=1.5)" );
        out.write( ForesterUtil.LINE_SEPARATOR );
        for( final DomainLengths domain_lengths : domain_lengths_list ) {
            final List<Species> species_list = domain_lengths.getMeanBasedOutlierSpecies( 1.5 );
            if ( species_list.size() > 0 ) {
                out.write( domain_lengths.getDomainId() + "\t" );
                for( final Species species : species_list ) {
                    out.write( species + "\t" );
                }
                out.write( ForesterUtil.LINE_SEPARATOR );
            }
        }
        out.write( ForesterUtil.LINE_SEPARATOR );
        out.write( ForesterUtil.LINE_SEPARATOR );
        out.write( "OUTLIER SPECIES (Z 1.0)" );
        out.write( ForesterUtil.LINE_SEPARATOR );
        final DescriptiveStatistics stats_for_all_species = domain_lengths_table
                .calculateMeanBasedStatisticsForAllSpecies();
        out.write( stats_for_all_species.asSummary() );
        out.write( ForesterUtil.LINE_SEPARATOR );
        final AsciiHistogram histo = new AsciiHistogram( stats_for_all_species );
        out.write( histo.toStringBuffer( 40, '=', 60, 4 ).toString() );
        out.write( ForesterUtil.LINE_SEPARATOR );
        final double population_sd = stats_for_all_species.sampleStandardDeviation();
        final double population_mean = stats_for_all_species.arithmeticMean();
        for( final Species species : domain_lengths_table.getSpecies() ) {
            final double x = domain_lengths_table.calculateMeanBasedStatisticsForSpecies( species ).arithmeticMean();
            final double z = ( x - population_mean ) / population_sd;
            out.write( species + "\t" + z );
            out.write( ForesterUtil.LINE_SEPARATOR );
        }
        out.write( ForesterUtil.LINE_SEPARATOR );
        for( final Species species : domain_lengths_table.getSpecies() ) {
            final DescriptiveStatistics stats_for_species = domain_lengths_table
                    .calculateMeanBasedStatisticsForSpecies( species );
            final double x = stats_for_species.arithmeticMean();
            final double z = ( x - population_mean ) / population_sd;
            if ( ( z <= -1.0 ) || ( z >= 1.0 ) ) {
                out.write( species + "\t" + df.format( z ) + "\t" + stats_for_species.asSummary() );
                out.write( ForesterUtil.LINE_SEPARATOR );
            }
        }
        out.close();
        System.gc();
    }

    /**
     * Warning: This side-effects 'all_bin_domain_combinations_encountered'!
     *
     *
     * @param output_file
     * @param all_bin_domain_combinations_changed
     * @param sum_of_all_domains_encountered
     * @param all_bin_domain_combinations_encountered
     * @param is_gains_analysis
     * @param protein_length_stats_by_dc
     * @throws IOException
     */
    public static void executeFitchGainsAnalysis( final File output_file,
                                                  final List<BinaryDomainCombination> all_bin_domain_combinations_changed,
                                                  final int sum_of_all_domains_encountered,
                                                  final SortedSet<BinaryDomainCombination> all_bin_domain_combinations_encountered,
                                                  final boolean is_gains_analysis )
            throws IOException {
        checkForOutputFileWriteability( output_file );
        final Writer out = ForesterUtil.createBufferedWriter( output_file );
        final SortedMap<Object, Integer> bdc_to_counts = ForesterUtil
                .listToSortedCountsMap( all_bin_domain_combinations_changed );
        final SortedSet<String> all_domains_in_combination_changed_more_than_once = new TreeSet<String>();
        final SortedSet<String> all_domains_in_combination_changed_only_once = new TreeSet<String>();
        int above_one = 0;
        int one = 0;
        for( final Object bdc_object : bdc_to_counts.keySet() ) {
            final BinaryDomainCombination bdc = ( BinaryDomainCombination ) bdc_object;
            final int count = bdc_to_counts.get( bdc_object );
            if ( count < 1 ) {
                ForesterUtil.unexpectedFatalError( surfacing.PRG_NAME, "count < 1 " );
            }
            out.write( bdc + "\t" + count + ForesterUtil.LINE_SEPARATOR );
            if ( count > 1 ) {
                all_domains_in_combination_changed_more_than_once.add( bdc.getId0() );
                all_domains_in_combination_changed_more_than_once.add( bdc.getId1() );
                above_one++;
            }
            else if ( count == 1 ) {
                all_domains_in_combination_changed_only_once.add( bdc.getId0() );
                all_domains_in_combination_changed_only_once.add( bdc.getId1() );
                one++;
            }
        }
        final int all = all_bin_domain_combinations_encountered.size();
        int never_lost = -1;
        if ( !is_gains_analysis ) {
            all_bin_domain_combinations_encountered.removeAll( all_bin_domain_combinations_changed );
            never_lost = all_bin_domain_combinations_encountered.size();
            for( final BinaryDomainCombination bdc : all_bin_domain_combinations_encountered ) {
                out.write( bdc + "\t" + "0" + ForesterUtil.LINE_SEPARATOR );
            }
        }
        if ( is_gains_analysis ) {
            out.write( "Sum of all distinct domain combinations appearing once               : " + one
                    + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domain combinations appearing more than once     : " + above_one
                    + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domains in combinations apppearing only once     : "
                    + all_domains_in_combination_changed_only_once.size() + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domains in combinations apppearing more than once: "
                    + all_domains_in_combination_changed_more_than_once.size() + ForesterUtil.LINE_SEPARATOR );
        }
        else {
            out.write( "Sum of all distinct domain combinations never lost                   : " + never_lost
                    + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domain combinations lost once                    : " + one
                    + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domain combinations lost more than once          : " + above_one
                    + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domains in combinations lost only once           : "
                    + all_domains_in_combination_changed_only_once.size() + ForesterUtil.LINE_SEPARATOR );
            out.write( "Sum of all distinct domains in combinations lost more than once: "
                    + all_domains_in_combination_changed_more_than_once.size() + ForesterUtil.LINE_SEPARATOR );
        }
        out.write( "All binary combinations                                              : " + all
                + ForesterUtil.LINE_SEPARATOR );
        out.write( "All domains                                                          : "
                + sum_of_all_domains_encountered );
        out.close();
        ForesterUtil
                .programMessage( surfacing.PRG_NAME,
                                 "Wrote fitch domain combination dynamics counts analysis to \"" + output_file + "\"" );
    }

    /**
     *
     * @param all_binary_domains_combination_lost_fitch
     * @param use_last_in_fitch_parsimony
     * @param perform_dc_fich
     * @param consider_directedness_and_adjacency_for_bin_combinations
     * @param all_binary_domains_combination_gained if null ignored, otherwise this is to list all binary domain combinations
     * which were gained under unweighted (Fitch) parsimony.
     */
    public static void executeParsimonyAnalysis( final long random_number_seed_for_fitch_parsimony,
                                                 final boolean radomize_fitch_parsimony,
                                                 final String outfile_name,
                                                 final DomainParsimonyCalculator domain_parsimony,
                                                 final Phylogeny phylogeny,
                                                 final Map<String, List<GoId>> domain_id_to_go_ids_map,
                                                 final Map<GoId, GoTerm> go_id_to_term_map,
                                                 final GoNameSpace go_namespace_limit,
                                                 final String parameters_str,
                                                 final Map<String, Set<String>>[] domain_id_to_secondary_features_maps,
                                                 final SortedSet<String> positive_filter,
                                                 final boolean output_binary_domain_combinations_for_graphs,
                                                 final List<BinaryDomainCombination> all_binary_domains_combination_gained_fitch,
                                                 final List<BinaryDomainCombination> all_binary_domains_combination_lost_fitch,
                                                 final BinaryDomainCombination.DomainCombinationType dc_type,
                                                 final Map<String, DescriptiveStatistics> protein_length_stats_by_dc,
                                                 final Map<String, DescriptiveStatistics> domain_number_stats_by_dc,
                                                 final Map<String, DescriptiveStatistics> domain_length_stats_by_domain,
                                                 final Map<String, Integer> tax_code_to_id_map,
                                                 final boolean write_to_nexus,
                                                 final boolean use_last_in_fitch_parsimony,
                                                 final boolean perform_dc_fich ) {
        final String sep = ForesterUtil.LINE_SEPARATOR + "###################" + ForesterUtil.LINE_SEPARATOR;
        final String date_time = ForesterUtil.getCurrentDateTime();
        final SortedSet<String> all_pfams_encountered = new TreeSet<String>();
        final SortedSet<String> all_pfams_gained_as_domains = new TreeSet<String>();
        final SortedSet<String> all_pfams_lost_as_domains = new TreeSet<String>();
        final SortedSet<String> all_pfams_gained_as_dom_combinations = new TreeSet<String>();
        final SortedSet<String> all_pfams_lost_as_dom_combinations = new TreeSet<String>();
        if ( write_to_nexus ) {
            writeToNexus( outfile_name, domain_parsimony, phylogeny );
        }
        // DOLLO DOMAINS
        // -------------
        Phylogeny local_phylogeny_l = phylogeny.copy();
        if ( ( positive_filter != null ) && ( positive_filter.size() > 0 ) ) {
            domain_parsimony.executeDolloParsimonyOnDomainPresence( positive_filter );
        }
        else {
            domain_parsimony.executeDolloParsimonyOnDomainPresence();
        }
        SurfacingUtil.writeMatrixToFile( domain_parsimony.getGainLossMatrix(),
                                         outfile_name + surfacing.PARSIMONY_OUTPUT_GL_SUFFIX_DOLLO_DOMAINS,
                                         Format.FORESTER );
        SurfacingUtil.writeMatrixToFile( domain_parsimony.getGainLossCountsMatrix(),
                                         outfile_name + surfacing.PARSIMONY_OUTPUT_GL_COUNTS_SUFFIX_DOLLO_DOMAINS,
                                         Format.FORESTER );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                           CharacterStateMatrix.GainLossStates.GAIN,
                                                           outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_GAINS_D,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                           CharacterStateMatrix.GainLossStates.LOSS,
                                                           outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_LOSSES_D,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                           null,
                                                           outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_PRESENT_D,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        //HTML:
        writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
                                       go_id_to_term_map,
                                       go_namespace_limit,
                                       false,
                                       domain_parsimony.getGainLossMatrix(),
                                       CharacterStateMatrix.GainLossStates.GAIN,
                                       outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_GAINS_HTML_D,
                                       sep,
                                       ForesterUtil.LINE_SEPARATOR,
                                       "Dollo Parsimony | Gains | Domains",
                                       "+",
                                       domain_id_to_secondary_features_maps,
                                       all_pfams_encountered,
                                       all_pfams_gained_as_domains,
                                       "_dollo_gains_d",
                                       tax_code_to_id_map );
        writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
                                       go_id_to_term_map,
                                       go_namespace_limit,
                                       false,
                                       domain_parsimony.getGainLossMatrix(),
                                       CharacterStateMatrix.GainLossStates.LOSS,
                                       outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_LOSSES_HTML_D,
                                       sep,
                                       ForesterUtil.LINE_SEPARATOR,
                                       "Dollo Parsimony | Losses | Domains",
                                       "-",
                                       domain_id_to_secondary_features_maps,
                                       all_pfams_encountered,
                                       all_pfams_lost_as_domains,
                                       "_dollo_losses_d",
                                       tax_code_to_id_map );
        writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
                                       go_id_to_term_map,
                                       go_namespace_limit,
                                       false,
                                       domain_parsimony.getGainLossMatrix(),
                                       null,
                                       outfile_name + surfacing.PARSIMONY_OUTPUT_DOLLO_PRESENT_HTML_D,
                                       sep,
                                       ForesterUtil.LINE_SEPARATOR,
                                       "Dollo Parsimony | Present | Domains",
                                       "",
                                       domain_id_to_secondary_features_maps,
                                       all_pfams_encountered,
                                       null,
                                       "_dollo_present_d",
                                       tax_code_to_id_map );
        preparePhylogeny( local_phylogeny_l,
                          domain_parsimony,
                          date_time,
                          "Dollo parsimony on domain presence/absence",
                          "dollo_on_domains_" + outfile_name,
                          parameters_str );
        SurfacingUtil.writePhylogenyToFile( local_phylogeny_l,
                                            outfile_name + surfacing.DOMAINS_PARSIMONY_TREE_OUTPUT_SUFFIX_DOLLO );
        try {
            writeAllDomainsChangedOnAllSubtrees( local_phylogeny_l, true, outfile_name, "_dollo_all_gains_d" );
            writeAllDomainsChangedOnAllSubtrees( local_phylogeny_l, false, outfile_name, "_dollo_all_losses_d" );
        }
        catch ( final IOException e ) {
            e.printStackTrace();
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
        }
        if ( perform_dc_fich && ( domain_parsimony.calculateNumberOfBinaryDomainCombination() > 0 ) ) {
            // FITCH DOMAIN COMBINATIONS
            // -------------------------
            local_phylogeny_l = phylogeny.copy();
            String randomization = "no";
            if ( radomize_fitch_parsimony ) {
                domain_parsimony
                        .executeFitchParsimonyOnBinaryDomainCombintion( random_number_seed_for_fitch_parsimony );
                randomization = "yes, seed = " + random_number_seed_for_fitch_parsimony;
            }
            else {
                domain_parsimony.executeFitchParsimonyOnBinaryDomainCombintion( use_last_in_fitch_parsimony );
            }
            SurfacingUtil.writeMatrixToFile( domain_parsimony.getGainLossMatrix(),
                                             outfile_name
                                                     + surfacing.PARSIMONY_OUTPUT_GL_SUFFIX_FITCH_BINARY_COMBINATIONS,
                                             Format.FORESTER );
            SurfacingUtil.writeMatrixToFile( domain_parsimony.getGainLossCountsMatrix(),
                                             outfile_name
                                                     + surfacing.PARSIMONY_OUTPUT_GL_COUNTS_SUFFIX_FITCH_BINARY_COMBINATIONS,
                                             Format.FORESTER );
            SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                               CharacterStateMatrix.GainLossStates.GAIN,
                                                               outfile_name + surfacing.PARSIMONY_OUTPUT_FITCH_GAINS_BC,
                                                               sep,
                                                               ForesterUtil.LINE_SEPARATOR,
                                                               null );
            SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                               CharacterStateMatrix.GainLossStates.LOSS,
                                                               outfile_name
                                                                       + surfacing.PARSIMONY_OUTPUT_FITCH_LOSSES_BC,
                                                               sep,
                                                               ForesterUtil.LINE_SEPARATOR,
                                                               null );
            SurfacingUtil.writeBinaryStatesMatrixAsListToFile( domain_parsimony.getGainLossMatrix(),
                                                               null,
                                                               outfile_name
                                                                       + surfacing.PARSIMONY_OUTPUT_FITCH_PRESENT_BC,
                                                               sep,
                                                               ForesterUtil.LINE_SEPARATOR,
                                                               null );
            if ( all_binary_domains_combination_gained_fitch != null ) {
                collectChangedDomainCombinationsFromBinaryStatesMatrixAsListToFile( domain_parsimony
                        .getGainLossMatrix(), dc_type, all_binary_domains_combination_gained_fitch, true );
            }
            if ( all_binary_domains_combination_lost_fitch != null ) {
                collectChangedDomainCombinationsFromBinaryStatesMatrixAsListToFile( domain_parsimony
                        .getGainLossMatrix(), dc_type, all_binary_domains_combination_lost_fitch, false );
            }
            if ( output_binary_domain_combinations_for_graphs ) {
                SurfacingUtil.writeBinaryStatesMatrixAsListToFileForBinaryCombinationsForGraphAnalysis( domain_parsimony
                        .getGainLossMatrix(),
                                                                                                        null,
                                                                                                        outfile_name
                                                                                                                + surfacing.PARSIMONY_OUTPUT_FITCH_PRESENT_BC_OUTPUTFILE_SUFFIX_FOR_GRAPH_ANALYSIS,
                                                                                                        sep,
                                                                                                        ForesterUtil.LINE_SEPARATOR,
                                                                                                        BinaryDomainCombination.OutputFormat.DOT );
            }
            // HTML:
            writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
                                           go_id_to_term_map,
                                           go_namespace_limit,
                                           true,
                                           domain_parsimony.getGainLossMatrix(),
                                           CharacterStateMatrix.GainLossStates.GAIN,
                                           outfile_name + surfacing.PARSIMONY_OUTPUT_FITCH_GAINS_HTML_BC,
                                           sep,
                                           ForesterUtil.LINE_SEPARATOR,
                                           "Fitch Parsimony | Gains | Domain Combinations",
                                           "+",
                                           null,
                                           all_pfams_encountered,
                                           all_pfams_gained_as_dom_combinations,
                                           "_fitch_gains_dc",
                                           tax_code_to_id_map );
            writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
                                           go_id_to_term_map,
                                           go_namespace_limit,
                                           true,
                                           domain_parsimony.getGainLossMatrix(),
                                           CharacterStateMatrix.GainLossStates.LOSS,
                                           outfile_name + surfacing.PARSIMONY_OUTPUT_FITCH_LOSSES_HTML_BC,
                                           sep,
                                           ForesterUtil.LINE_SEPARATOR,
                                           "Fitch Parsimony | Losses | Domain Combinations",
                                           "-",
                                           null,
                                           all_pfams_encountered,
                                           all_pfams_lost_as_dom_combinations,
                                           "_fitch_losses_dc",
                                           tax_code_to_id_map );
            //            writeBinaryStatesMatrixToList( domain_id_to_go_ids_map,
            //                                           go_id_to_term_map,
            //                                           go_namespace_limit,
            //                                           true,
            //                                           domain_parsimony.getGainLossMatrix(),
            //                                           null,
            //                                           outfile_name + surfacing.PARSIMONY_OUTPUT_FITCH_PRESENT_HTML_BC,
            //                                           sep,
            //                                           ForesterUtil.LINE_SEPARATOR,
            //                                           "Fitch Parsimony | Present | Domain Combinations",
            //                                           "",
            //                                           null,
            //                                           all_pfams_encountered,
            //                                           null,
            //                                           "_fitch_present_dc",
            //                                           tax_code_to_id_map );
            writeAllEncounteredPfamsToFile( domain_id_to_go_ids_map,
                                            go_id_to_term_map,
                                            outfile_name,
                                            all_pfams_encountered );
            writePfamsToFile( outfile_name + surfacing.ALL_PFAMS_GAINED_AS_DOMAINS_SUFFIX,
                              all_pfams_gained_as_domains );
            writePfamsToFile( outfile_name + surfacing.ALL_PFAMS_LOST_AS_DOMAINS_SUFFIX, all_pfams_lost_as_domains );
            writePfamsToFile( outfile_name + surfacing.ALL_PFAMS_GAINED_AS_DC_SUFFIX,
                              all_pfams_gained_as_dom_combinations );
            writePfamsToFile( outfile_name + surfacing.ALL_PFAMS_LOST_AS_DC_SUFFIX,
                              all_pfams_lost_as_dom_combinations );
            preparePhylogeny( local_phylogeny_l,
                              domain_parsimony,
                              date_time,
                              "Fitch parsimony on binary domain combination presence/absence randomization: "
                                      + randomization,
                              "fitch_on_binary_domain_combinations_" + outfile_name,
                              parameters_str );
            SurfacingUtil
                    .writePhylogenyToFile( local_phylogeny_l,
                                           outfile_name
                                                   + surfacing.BINARY_DOMAIN_COMBINATIONS_PARSIMONY_TREE_OUTPUT_SUFFIX_FITCH );
            calculateIndependentDomainCombinationGains( local_phylogeny_l,
                                                        outfile_name
                                                                + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_COUNTS_OUTPUT_SUFFIX,
                                                        outfile_name
                                                                + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_OUTPUT_SUFFIX,
                                                        outfile_name
                                                                + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_FOR_GO_MAPPING_OUTPUT_SUFFIX,
                                                        outfile_name
                                                                + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_FOR_GO_MAPPING_OUTPUT_UNIQUE_SUFFIX,
                                                        outfile_name + "_indep_dc_gains_fitch_lca_ranks.txt",
                                                        outfile_name + "_indep_dc_gains_fitch_lca_taxonomies.txt",
                                                        outfile_name + "_indep_dc_gains_fitch_protein_statistics.txt",
                                                        protein_length_stats_by_dc,
                                                        domain_number_stats_by_dc,
                                                        domain_length_stats_by_domain );
        }
    }

    public static void executeParsimonyAnalysisForSecondaryFeatures( final String outfile_name,
                                                                     final DomainParsimonyCalculator secondary_features_parsimony,
                                                                     final Phylogeny phylogeny,
                                                                     final String parameters_str,
                                                                     final Map<Species, MappingResults> mapping_results_map,
                                                                     final boolean use_last_in_fitch_parsimony ) {
        final String sep = ForesterUtil.LINE_SEPARATOR + "###################" + ForesterUtil.LINE_SEPARATOR;
        final String date_time = ForesterUtil.getCurrentDateTime();
        System.out.println();
        writeToNexus( outfile_name + surfacing.NEXUS_SECONDARY_FEATURES,
                      secondary_features_parsimony.createMatrixOfSecondaryFeaturePresenceOrAbsence( null ),
                      phylogeny );
        Phylogeny local_phylogeny_copy = phylogeny.copy();
        secondary_features_parsimony.executeDolloParsimonyOnSecondaryFeatures( mapping_results_map );
        SurfacingUtil.writeMatrixToFile( secondary_features_parsimony.getGainLossMatrix(),
                                         outfile_name + surfacing.PARSIMONY_OUTPUT_GL_SUFFIX_DOLLO_SECONDARY_FEATURES,
                                         Format.FORESTER );
        SurfacingUtil.writeMatrixToFile( secondary_features_parsimony.getGainLossCountsMatrix(),
                                         outfile_name
                                                 + surfacing.PARSIMONY_OUTPUT_GL_COUNTS_SUFFIX_DOLLO_SECONDARY_FEATURES,
                                         Format.FORESTER );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( secondary_features_parsimony.getGainLossMatrix(),
                                                           CharacterStateMatrix.GainLossStates.GAIN,
                                                           outfile_name
                                                                   + surfacing.PARSIMONY_OUTPUT_DOLLO_GAINS_SECONDARY_FEATURES,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( secondary_features_parsimony.getGainLossMatrix(),
                                                           CharacterStateMatrix.GainLossStates.LOSS,
                                                           outfile_name
                                                                   + surfacing.PARSIMONY_OUTPUT_DOLLO_LOSSES_SECONDARY_FEATURES,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        SurfacingUtil.writeBinaryStatesMatrixAsListToFile( secondary_features_parsimony.getGainLossMatrix(),
                                                           null,
                                                           outfile_name
                                                                   + surfacing.PARSIMONY_OUTPUT_DOLLO_PRESENT_SECONDARY_FEATURES,
                                                           sep,
                                                           ForesterUtil.LINE_SEPARATOR,
                                                           null );
        preparePhylogeny( local_phylogeny_copy,
                          secondary_features_parsimony,
                          date_time,
                          "Dollo parsimony on secondary feature presence/absence",
                          "dollo_on_secondary_features_" + outfile_name,
                          parameters_str );
        SurfacingUtil
                .writePhylogenyToFile( local_phylogeny_copy,
                                       outfile_name + surfacing.SECONDARY_FEATURES_PARSIMONY_TREE_OUTPUT_SUFFIX_DOLLO );
        // FITCH DOMAIN COMBINATIONS
        // -------------------------
        local_phylogeny_copy = phylogeny.copy();
        final String randomization = "no";
        secondary_features_parsimony
                .executeFitchParsimonyOnBinaryDomainCombintionOnSecondaryFeatures( use_last_in_fitch_parsimony );
        preparePhylogeny( local_phylogeny_copy,
                          secondary_features_parsimony,
                          date_time,
                          "Fitch parsimony on secondary binary domain combination presence/absence randomization: "
                                  + randomization,
                          "fitch_on_binary_domain_combinations_" + outfile_name,
                          parameters_str );
        SurfacingUtil
                .writePhylogenyToFile( local_phylogeny_copy,
                                       outfile_name
                                               + surfacing.BINARY_DOMAIN_COMBINATIONS_PARSIMONY_TREE_OUTPUT_SUFFIX_FITCH_MAPPED );
        calculateIndependentDomainCombinationGains( local_phylogeny_copy,
                                                    outfile_name
                                                            + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_COUNTS_MAPPED_OUTPUT_SUFFIX,
                                                    outfile_name
                                                            + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_MAPPED_OUTPUT_SUFFIX,
                                                    outfile_name
                                                            + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_FOR_GO_MAPPING_MAPPED_OUTPUT_SUFFIX,
                                                    outfile_name
                                                            + surfacing.INDEPENDENT_DC_GAINS_FITCH_PARS_DC_FOR_GO_MAPPING_MAPPED_OUTPUT_UNIQUE_SUFFIX,
                                                    outfile_name + "_MAPPED_indep_dc_gains_fitch_lca_ranks.txt",
                                                    outfile_name + "_MAPPED_indep_dc_gains_fitch_lca_taxonomies.txt",
                                                    null,
                                                    null,
                                                    null,
                                                    null );
    }

    public static void executePlusMinusAnalysis( final File output_file,
                                                 final List<String> plus_minus_analysis_high_copy_base,
                                                 final List<String> plus_minus_analysis_high_copy_target,
                                                 final List<String> plus_minus_analysis_low_copy,
                                                 final List<GenomeWideCombinableDomains> gwcd_list,
                                                 final SortedMap<Species, List<Protein>> protein_lists_per_species,
                                                 final Map<String, List<GoId>> domain_id_to_go_ids_map,
                                                 final Map<GoId, GoTerm> go_id_to_term_map,
                                                 final List<Object> plus_minus_analysis_numbers ) {
        final Set<String> all_spec = new HashSet<String>();
        for( final GenomeWideCombinableDomains gwcd : gwcd_list ) {
            all_spec.add( gwcd.getSpecies().getSpeciesId() );
        }
        final File html_out_dom = new File( output_file + surfacing.PLUS_MINUS_DOM_SUFFIX_HTML );
        final File plain_out_dom = new File( output_file + surfacing.PLUS_MINUS_DOM_SUFFIX );
        final File html_out_dc = new File( output_file + surfacing.PLUS_MINUS_DC_SUFFIX_HTML );
        final File all_domains_go_ids_out_dom = new File( output_file + surfacing.PLUS_MINUS_ALL_GO_IDS_DOM_SUFFIX );
        final File passing_domains_go_ids_out_dom = new File( output_file
                + surfacing.PLUS_MINUS_PASSING_GO_IDS_DOM_SUFFIX );
        final File proteins_file_base = new File( output_file + "" );
        final int min_diff = ( ( Integer ) plus_minus_analysis_numbers.get( 0 ) ).intValue();
        final double factor = ( ( Double ) plus_minus_analysis_numbers.get( 1 ) ).doubleValue();
        try {
            DomainCountsDifferenceUtil.calculateCopyNumberDifferences( gwcd_list,
                                                                       protein_lists_per_species,
                                                                       plus_minus_analysis_high_copy_base,
                                                                       plus_minus_analysis_high_copy_target,
                                                                       plus_minus_analysis_low_copy,
                                                                       min_diff,
                                                                       factor,
                                                                       plain_out_dom,
                                                                       html_out_dom,
                                                                       html_out_dc,
                                                                       domain_id_to_go_ids_map,
                                                                       go_id_to_term_map,
                                                                       all_domains_go_ids_out_dom,
                                                                       passing_domains_go_ids_out_dom,
                                                                       proteins_file_base );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote plus minus domain analysis results to \"" + html_out_dom + "\"" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote plus minus domain analysis results to \"" + plain_out_dom + "\"" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote plus minus domain analysis results to \"" + html_out_dc + "\"" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote plus minus domain analysis based passing GO ids to \""
                                             + passing_domains_go_ids_out_dom + "\"" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote plus minus domain analysis based all GO ids to \""
                                             + all_domains_go_ids_out_dom + "\"" );
    }

    public static void extractProteinNames( final List<Protein> proteins,
                                            final List<String> query_domain_ids_nc_order,
                                            final Writer out,
                                            final String separator,
                                            final String limit_to_species )
            throws IOException {
        for( final Protein protein : proteins ) {
            if ( ForesterUtil.isEmpty( limit_to_species )
                    || protein.getSpecies().getSpeciesId().equalsIgnoreCase( limit_to_species ) ) {
                if ( protein.contains( query_domain_ids_nc_order, true ) ) {
                    out.write( protein.getSpecies().getSpeciesId() );
                    out.write( separator );
                    out.write( protein.getProteinId().getId() );
                    out.write( separator );
                    out.write( "[" );
                    final Set<String> visited_domain_ids = new HashSet<String>();
                    boolean first = true;
                    for( final Domain domain : protein.getProteinDomains() ) {
                        if ( !visited_domain_ids.contains( domain.getDomainId() ) ) {
                            visited_domain_ids.add( domain.getDomainId() );
                            if ( first ) {
                                first = false;
                            }
                            else {
                                out.write( " " );
                            }
                            out.write( domain.getDomainId() );
                            out.write( " {" );
                            out.write( "" + domain.getTotalCount() );
                            out.write( "}" );
                        }
                    }
                    out.write( "]" );
                    out.write( separator );
                    if ( !( ForesterUtil.isEmpty( protein.getDescription() )
                            || protein.getDescription().equals( SurfacingConstants.NONE ) ) ) {
                        out.write( protein.getDescription() );
                    }
                    out.write( separator );
                    if ( !( ForesterUtil.isEmpty( protein.getAccession() )
                            || protein.getAccession().equals( SurfacingConstants.NONE ) ) ) {
                        out.write( protein.getAccession() );
                    }
                    out.write( SurfacingConstants.NL );
                }
            }
        }
        out.flush();
    }

    public static void extractProteinNames( final SortedMap<Species, List<Protein>> protein_lists_per_species,
                                            final String domain_id,
                                            final Writer out,
                                            final String separator,
                                            final String limit_to_species,
                                            final double domain_e_cutoff )
            throws IOException {
        //System.out.println( "Per domain E-value: " + domain_e_cutoff );
        for( final Species species : protein_lists_per_species.keySet() ) {
            //System.out.println( species + ":" );
            for( final Protein protein : protein_lists_per_species.get( species ) ) {
                if ( ForesterUtil.isEmpty( limit_to_species )
                        || protein.getSpecies().getSpeciesId().equalsIgnoreCase( limit_to_species ) ) {
                    final List<Domain> domains = protein.getProteinDomains( domain_id );
                    if ( domains.size() > 0 ) {
                        out.write( protein.getSpecies().getSpeciesId() );
                        out.write( separator );
                        out.write( protein.getProteinId().getId() );
                        out.write( separator );
                        out.write( domain_id.toString() );
                        out.write( separator );
                        int prev_to = -1;
                        for( final Domain domain : domains ) {
                            if ( ( domain_e_cutoff < 0 ) || ( domain.getPerDomainEvalue() <= domain_e_cutoff ) ) {
                                out.write( "/" );
                                out.write( domain.getFrom() + "-" + domain.getTo() );
                                if ( prev_to >= 0 ) {
                                    final int l = domain.getFrom() - prev_to;
                                    // System.out.println( l );
                                }
                                prev_to = domain.getTo();
                            }
                        }
                        out.write( "/" );
                        out.write( separator );
                        final List<Domain> domain_list = new ArrayList<Domain>();
                        for( final Domain domain : protein.getProteinDomains() ) {
                            if ( ( domain_e_cutoff < 0 ) || ( domain.getPerDomainEvalue() <= domain_e_cutoff ) ) {
                                domain_list.add( domain );
                            }
                        }
                        final Domain domain_ary[] = new Domain[ domain_list.size() ];
                        for( int i = 0; i < domain_list.size(); ++i ) {
                            domain_ary[ i ] = domain_list.get( i );
                        }
                        Arrays.sort( domain_ary, new DomainComparator( true ) );
                        out.write( "{" );
                        boolean first = true;
                        for( final Domain domain : domain_ary ) {
                            if ( first ) {
                                first = false;
                            }
                            else {
                                out.write( "," );
                            }
                            out.write( domain.getDomainId().toString() );
                            out.write( ":" + domain.getFrom() + "-" + domain.getTo() );
                            out.write( ":" + domain.getPerDomainEvalue() );
                        }
                        out.write( "}" );
                        if ( !( ForesterUtil.isEmpty( protein.getDescription() )
                                || protein.getDescription().equals( SurfacingConstants.NONE ) ) ) {
                            out.write( protein.getDescription() );
                        }
                        out.write( separator );
                        if ( !( ForesterUtil.isEmpty( protein.getAccession() )
                                || protein.getAccession().equals( SurfacingConstants.NONE ) ) ) {
                            out.write( protein.getAccession() );
                        }
                        out.write( SurfacingConstants.NL );
                    }
                }
            }
        }
        out.flush();
    }

    public static SortedSet<String> getAllDomainIds( final List<GenomeWideCombinableDomains> gwcd_list ) {
        final SortedSet<String> all_domains_ids = new TreeSet<String>();
        for( final GenomeWideCombinableDomains gwcd : gwcd_list ) {
            final Set<String> all_domains = gwcd.getAllDomainIds();
            //    for( final Domain domain : all_domains ) {
            all_domains_ids.addAll( all_domains );
            //    }
        }
        return all_domains_ids;
    }

    public static SortedMap<String, Integer> getDomainCounts( final List<Protein> protein_domain_collections ) {
        final SortedMap<String, Integer> map = new TreeMap<String, Integer>();
        for( final Protein protein_domain_collection : protein_domain_collections ) {
            for( final Object name : protein_domain_collection.getProteinDomains() ) {
                final BasicDomain protein_domain = ( BasicDomain ) name;
                final String id = protein_domain.getDomainId();
                if ( map.containsKey( id ) ) {
                    map.put( id, map.get( id ) + 1 );
                }
                else {
                    map.put( id, 1 );
                }
            }
        }
        return map;
    }

    public static int getNumberOfNodesLackingName( final Phylogeny p, final StringBuilder names ) {
        final PhylogenyNodeIterator it = p.iteratorPostorder();
        int c = 0;
        while ( it.hasNext() ) {
            final PhylogenyNode n = it.next();
            if ( ForesterUtil.isEmpty( n.getName() )
                    && ( !n.getNodeData().isHasTaxonomy()
                            || ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getScientificName() ) )
                    && ( !n.getNodeData().isHasTaxonomy()
                            || ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getCommonName() ) ) ) {
                if ( n.getParent() != null ) {
                    names.append( " " );
                    names.append( n.getParent().getName() );
                }
                final List l = n.getAllExternalDescendants();
                for( final Object object : l ) {
                    System.out.println( l.toString() );
                }
                ++c;
            }
        }
        return c;
    }

    public static void log( final String msg, final Writer w ) {
        try {
            w.write( msg );
            w.write( ForesterUtil.LINE_SEPARATOR );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
        }
    }

    public static Phylogeny[] obtainAndPreProcessIntrees( final File[] intree_files,
                                                          final int number_of_genomes,
                                                          final String[][] input_file_properties ) {
        final Phylogeny[] intrees = new Phylogeny[ intree_files.length ];
        int i = 0;
        for( final File intree_file : intree_files ) {
            Phylogeny intree = null;
            final String error = ForesterUtil.isReadableFile( intree_file );
            if ( !ForesterUtil.isEmpty( error ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "cannot read input tree file [" + intree_file + "]: " + error );
            }
            try {
                final Phylogeny[] p_array = ParserBasedPhylogenyFactory.getInstance()
                        .create( intree_file, ParserUtils.createParserDependingOnFileType( intree_file, true ) );
                if ( p_array.length < 1 ) {
                    ForesterUtil.fatalError( surfacing.PRG_NAME,
                                             "file [" + intree_file
                                                     + "] does not contain any phylogeny in phyloXML format" );
                }
                else if ( p_array.length > 1 ) {
                    ForesterUtil.fatalError( surfacing.PRG_NAME,
                                             "file [" + intree_file
                                                     + "] contains more than one phylogeny in phyloXML format" );
                }
                intree = p_array[ 0 ];
            }
            catch ( final Exception e ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "failed to read input tree from file [" + intree_file + "]: " + error );
            }
            if ( ( intree == null ) || intree.isEmpty() ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME, "input tree [" + intree_file + "] is empty" );
            }
            if ( !intree.isRooted() ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME, "input tree [" + intree_file + "] is not rooted" );
            }
            final StringBuilder parent_names = new StringBuilder();
            final int nodes_lacking_name = getNumberOfNodesLackingName( intree, parent_names );
            if ( nodes_lacking_name > 0 ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "input tree [" + intree_file + "] has " + nodes_lacking_name
                                                 + " node(s) lacking a name [parent names:" + parent_names + "]" );
            }
            preparePhylogenyForParsimonyAnalyses( intree, input_file_properties );
            if ( !intree.isCompletelyBinary() ) {
                ForesterUtil.printWarningMessage( surfacing.PRG_NAME,
                                                  "input tree [" + intree_file + "] is not completely binary" );
            }
            intrees[ i++ ] = intree;
        }
        return intrees;
    }

    public static Phylogeny obtainFirstIntree( final File intree_file ) {
        Phylogeny intree = null;
        final String error = ForesterUtil.isReadableFile( intree_file );
        if ( !ForesterUtil.isEmpty( error ) ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME,
                                     "cannot read input tree file [" + intree_file + "]: " + error );
        }
        try {
            final Phylogeny[] phys = ParserBasedPhylogenyFactory.getInstance()
                    .create( intree_file, ParserUtils.createParserDependingOnFileType( intree_file, true ) );
            if ( phys.length < 1 ) {
                ForesterUtil
                        .fatalError( surfacing.PRG_NAME,
                                     "file [" + intree_file + "] does not contain any phylogeny in phyloXML format" );
            }
            else if ( phys.length > 1 ) {
                ForesterUtil
                        .fatalError( surfacing.PRG_NAME,
                                     "file [" + intree_file + "] contains more than one phylogeny in phyloXML format" );
            }
            intree = phys[ 0 ];
        }
        catch ( final Exception e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME,
                                     "failed to read input tree from file [" + intree_file + "]: " + error );
        }
        if ( ( intree == null ) || intree.isEmpty() ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, "input tree [" + intree_file + "] is empty" );
        }
        if ( !intree.isRooted() ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, "input tree [" + intree_file + "] is not rooted" );
        }
        return intree;
    }

    public static String obtainHexColorStringDependingOnTaxonomyGroup( final String tax_code, final Phylogeny phy )
            throws IllegalArgumentException {
        if ( !_TAXCODE_HEXCOLORSTRING_MAP.containsKey( tax_code ) ) {
            if ( ( phy != null ) && !phy.isEmpty() ) {
                //                final List<PhylogenyNode> nodes = phy.getNodesViaTaxonomyCode( tax_code );
                //                Color c = null;
                //                if ( ( nodes == null ) || nodes.isEmpty() ) {
                //                    throw new IllegalArgumentException( "code " + tax_code + " is not found" );
                //                }
                //                if ( nodes.size() != 1 ) {
                //                    throw new IllegalArgumentException( "code " + tax_code + " is not unique" );
                //                }
                //                PhylogenyNode n = nodes.get( 0 );
                //                while ( n != null ) {
                //                    if ( n.getNodeData().isHasTaxonomy()
                //                            && !ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getScientificName() ) ) {
                //                        c = ForesterUtil.obtainColorDependingOnTaxonomyGroup( n.getNodeData().getTaxonomy()
                //                                .getScientificName(), tax_code );
                //                    }
                //                    if ( ( c == null ) && !ForesterUtil.isEmpty( n.getName() ) ) {
                //                        c = ForesterUtil.obtainColorDependingOnTaxonomyGroup( n.getName(), tax_code );
                //                    }
                //                    if ( c != null ) {
                //                        break;
                //                    }
                //                    n = n.getParent();
                //                }
                final String group = obtainTaxonomyGroup( tax_code, phy );
                final Color c = ForesterUtil.obtainColorDependingOnTaxonomyGroup( group );
                if ( c == null ) {
                    throw new IllegalArgumentException( "no color found for taxonomy group \"" + group
                            + "\" for code \"" + tax_code + "\"" );
                }
                final String hex = String.format( "#%02x%02x%02x", c.getRed(), c.getGreen(), c.getBlue() );
                _TAXCODE_HEXCOLORSTRING_MAP.put( tax_code, hex );
            }
            else {
                throw new IllegalArgumentException( "unable to obtain color for code " + tax_code
                        + " (tree is null or empty and code is not in map)" );
            }
        }
        return _TAXCODE_HEXCOLORSTRING_MAP.get( tax_code );
    }

    public static String obtainTaxonomyGroup( final String tax_code, final Phylogeny species_tree )
            throws IllegalArgumentException {
        if ( !_TAXCODE_TAXGROUP_MAP.containsKey( tax_code ) ) {
            if ( ( species_tree != null ) && !species_tree.isEmpty() ) {
                final List<PhylogenyNode> nodes = species_tree.getNodesViaTaxonomyCode( tax_code );
                if ( ( nodes == null ) || nodes.isEmpty() ) {
                    throw new IllegalArgumentException( "code " + tax_code + " is not found" );
                }
                if ( nodes.size() != 1 ) {
                    throw new IllegalArgumentException( "code " + tax_code + " is not unique" );
                }
                PhylogenyNode n = nodes.get( 0 );
                String group = null;
                while ( n != null ) {
                    if ( n.getNodeData().isHasTaxonomy()
                            && !ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getScientificName() ) ) {
                        group = ForesterUtil
                                .obtainNormalizedTaxonomyGroup( n.getNodeData().getTaxonomy().getScientificName() );
                    }
                    if ( ForesterUtil.isEmpty( group ) && !ForesterUtil.isEmpty( n.getName() ) ) {
                        group = ForesterUtil.obtainNormalizedTaxonomyGroup( n.getName() );
                    }
                    if ( !ForesterUtil.isEmpty( group ) ) {
                        break;
                    }
                    n = n.getParent();
                }
                if ( ForesterUtil.isEmpty( group ) ) {
                    group = TaxonomyGroups.OTHER;
                }
                _TAXCODE_TAXGROUP_MAP.put( tax_code, group );
            }
            else {
                throw new IllegalArgumentException( "unable to obtain group for code " + tax_code
                        + " (tree is null or empty and code is not in map)" );
            }
        }
        return _TAXCODE_TAXGROUP_MAP.get( tax_code );
    }

    public static void performDomainArchitectureAnalysis( final SortedMap<String, Set<String>> domain_architecutures,
                                                          final SortedMap<String, Integer> domain_architecuture_counts,
                                                          final int min_count,
                                                          final File da_counts_outfile,
                                                          final File unique_da_outfile ) {
        checkForOutputFileWriteability( da_counts_outfile );
        checkForOutputFileWriteability( unique_da_outfile );
        try {
            final BufferedWriter da_counts_out = new BufferedWriter( new FileWriter( da_counts_outfile ) );
            final BufferedWriter unique_da_out = new BufferedWriter( new FileWriter( unique_da_outfile ) );
            final Iterator<Entry<String, Integer>> it = domain_architecuture_counts.entrySet().iterator();
            while ( it.hasNext() ) {
                final Map.Entry<String, Integer> e = it.next();
                final String da = e.getKey();
                final int count = e.getValue();
                if ( count >= min_count ) {
                    da_counts_out.write( da );
                    da_counts_out.write( "\t" );
                    da_counts_out.write( String.valueOf( count ) );
                    da_counts_out.write( ForesterUtil.LINE_SEPARATOR );
                }
                if ( count == 1 ) {
                    final Iterator<Entry<String, Set<String>>> it2 = domain_architecutures.entrySet().iterator();
                    while ( it2.hasNext() ) {
                        final Map.Entry<String, Set<String>> e2 = it2.next();
                        final String genome = e2.getKey();
                        final Set<String> das = e2.getValue();
                        if ( das.contains( da ) ) {
                            unique_da_out.write( genome );
                            unique_da_out.write( "\t" );
                            unique_da_out.write( da );
                            unique_da_out.write( ForesterUtil.LINE_SEPARATOR );
                        }
                    }
                }
            }
            unique_da_out.close();
            da_counts_out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote distance matrices to \"" + da_counts_outfile + "\"" );
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote distance matrices to \"" + unique_da_outfile + "\"" );
        //
    }

    public static void preparePhylogeny( final Phylogeny p,
                                         final DomainParsimonyCalculator domain_parsimony,
                                         final String date_time,
                                         final String method,
                                         final String name,
                                         final String parameters_str ) {
        domain_parsimony.decoratePhylogenyWithDomains( p );
        final StringBuilder desc = new StringBuilder();
        desc.append( "[Method: " + method + "] [Date: " + date_time + "] " );
        desc.append( "[Cost: " + domain_parsimony.getCost() + "] " );
        desc.append( "[Gains: " + domain_parsimony.getTotalGains() + "] " );
        desc.append( "[Losses: " + domain_parsimony.getTotalLosses() + "] " );
        desc.append( "[Unchanged: " + domain_parsimony.getTotalUnchanged() + "] " );
        desc.append( "[Parameters: " + parameters_str + "]" );
        p.setName( name );
        p.setDescription( desc.toString() );
        p.setConfidence( new Confidence( domain_parsimony.getCost(), "parsimony" ) );
        p.setRerootable( false );
        p.setRooted( true );
    }

    public static void preparePhylogenyForParsimonyAnalyses( final Phylogeny intree,
                                                             final String[][] input_file_properties ) {
        final String[] genomes = new String[ input_file_properties.length ];
        for( int i = 0; i < input_file_properties.length; ++i ) {
            if ( intree.getNodes( input_file_properties[ i ][ 1 ] ).size() > 1 ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "node named [" + input_file_properties[ i ][ 1 ]
                                                 + "] is not unique in input tree " + intree.getName() );
            }
            genomes[ i ] = input_file_properties[ i ][ 1 ];
        }
        //
        final PhylogenyNodeIterator it = intree.iteratorPostorder();
        while ( it.hasNext() ) {
            final PhylogenyNode n = it.next();
            if ( ForesterUtil.isEmpty( n.getName() ) ) {
                if ( n.getNodeData().isHasTaxonomy()
                        && !ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getTaxonomyCode() ) ) {
                    n.setName( n.getNodeData().getTaxonomy().getTaxonomyCode() );
                }
                else if ( n.getNodeData().isHasTaxonomy()
                        && !ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getScientificName() ) ) {
                    n.setName( n.getNodeData().getTaxonomy().getScientificName() );
                }
                else if ( n.getNodeData().isHasTaxonomy()
                        && !ForesterUtil.isEmpty( n.getNodeData().getTaxonomy().getCommonName() ) ) {
                    n.setName( n.getNodeData().getTaxonomy().getCommonName() );
                }
                else {
                    ForesterUtil
                            .fatalError( surfacing.PRG_NAME,
                                         "node with no name, scientific name, common name, or taxonomy code present" );
                }
            }
        }
        final List<String> igns = PhylogenyMethods.deleteExternalNodesPositiveSelection( genomes, intree );
        if ( igns.size() > 0 ) {
            System.out.println( "Not using the following " + igns.size() + " nodes:" );
            for( int i = 0; i < igns.size(); ++i ) {
                System.out.println( " " + i + ": " + igns.get( i ) );
            }
            System.out.println( "--" );
        }
        //Test for node names:
        final SortedSet<String> not_found = new TreeSet<String>();
        final SortedSet<String> not_unique = new TreeSet<String>();
        for( final String[] input_file_propertie : input_file_properties ) {
            final String name = input_file_propertie[ 1 ];
            final List<PhylogenyNode> nodes = intree.getNodes( name );
            if ( ( nodes == null ) || ( nodes.size() < 1 ) ) {
                not_found.add( name );
            }
            if ( nodes.size() > 1 ) {
                not_unique.add( name );
            }
        }
        if ( not_found.size() > 0 ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME,
                                     "the following " + not_found.size()
                                             + " node(s) are not present in the input tree: " + not_found );
        }
        if ( not_unique.size() > 0 ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME,
                                     "the following " + not_unique.size()
                                             + " node(s) are not unique in the input tree: " + not_unique );
        }
    }

    public static void printOutPercentageOfMultidomainProteins( final SortedMap<Integer, Integer> all_genomes_domains_per_potein_histo,
                                                                final Writer log_writer ) {
        int sum = 0;
        for( final Entry<Integer, Integer> entry : all_genomes_domains_per_potein_histo.entrySet() ) {
            sum += entry.getValue();
        }
        final double percentage = ( 100.0 * ( sum - all_genomes_domains_per_potein_histo.get( 1 ) ) ) / sum;
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Percentage of multidomain proteins: " + percentage + "%" );
        log( "Percentage of multidomain proteins:            : " + percentage + "%", log_writer );
    }

    public static void processFilter( final File filter_file, final SortedSet<String> filter ) {
        SortedSet<String> filter_str = null;
        try {
            filter_str = ForesterUtil.file2set( filter_file );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        if ( filter_str != null ) {
            for( final String string : filter_str ) {
                filter.add( string );
            }
        }
        if ( surfacing.VERBOSE ) {
            System.out.println( "Filter:" );
            for( final String domainId : filter ) {
                System.out.println( domainId );
            }
        }
    }

    public static String[][] processInputGenomesFile( final File input_genomes ) {
        String[][] input_file_properties = null;
        try {
            input_file_properties = ForesterUtil.file22dArray( input_genomes );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME,
                                     "genomes files is to be in the following format \"<hmmpfam output file> <species>\": "
                                             + e.getLocalizedMessage() );
        }
        final Set<String> specs = new HashSet<String>();
        final Set<String> paths = new HashSet<String>();
        for( int i = 0; i < input_file_properties.length; ++i ) {
            if ( !PhyloXmlUtil.TAXOMONY_CODE_PATTERN.matcher( input_file_properties[ i ][ 1 ] ).matches() ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "illegal format for species code: " + input_file_properties[ i ][ 1 ] );
            }
            if ( specs.contains( input_file_properties[ i ][ 1 ] ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "species code " + input_file_properties[ i ][ 1 ] + " is not unique" );
            }
            specs.add( input_file_properties[ i ][ 1 ] );
            if ( paths.contains( input_file_properties[ i ][ 0 ] ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "path " + input_file_properties[ i ][ 0 ] + " is not unique" );
            }
            paths.add( input_file_properties[ i ][ 0 ] );
            final String error = ForesterUtil.isReadableFile( new File( input_file_properties[ i ][ 0 ] ) );
            if ( !ForesterUtil.isEmpty( error ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME, error );
            }
        }
        return input_file_properties;
    }

    public static void processPlusMinusAnalysisOption( final CommandLineArguments cla,
                                                       final List<String> high_copy_base,
                                                       final List<String> high_copy_target,
                                                       final List<String> low_copy,
                                                       final List<Object> numbers ) {
        if ( cla.isOptionSet( surfacing.PLUS_MINUS_ANALYSIS_OPTION ) ) {
            if ( !cla.isOptionValueSet( surfacing.PLUS_MINUS_ANALYSIS_OPTION ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME,
                                         "no value for 'plus-minus' file: -" + surfacing.PLUS_MINUS_ANALYSIS_OPTION
                                                 + "=<file>" );
            }
            final File plus_minus_file = new File( cla.getOptionValue( surfacing.PLUS_MINUS_ANALYSIS_OPTION ) );
            final String msg = ForesterUtil.isReadableFile( plus_minus_file );
            if ( !ForesterUtil.isEmpty( msg ) ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME, "can not read from \"" + plus_minus_file + "\": " + msg );
            }
            processPlusMinusFile( plus_minus_file, high_copy_base, high_copy_target, low_copy, numbers );
        }
    }

    // First numbers is minimal difference, second is factor.
    public static void processPlusMinusFile( final File plus_minus_file,
                                             final List<String> high_copy_base,
                                             final List<String> high_copy_target,
                                             final List<String> low_copy,
                                             final List<Object> numbers ) {
        Set<String> species_set = null;
        int min_diff = surfacing.PLUS_MINUS_ANALYSIS_MIN_DIFF_DEFAULT;
        double factor = surfacing.PLUS_MINUS_ANALYSIS_FACTOR_DEFAULT;
        try {
            species_set = ForesterUtil.file2set( plus_minus_file );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        if ( species_set != null ) {
            for( final String species : species_set ) {
                final String species_trimmed = species.substring( 1 );
                if ( species.startsWith( "+" ) ) {
                    if ( low_copy.contains( species_trimmed ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME,
                                                 "species/genome names can not appear with both '+' and '-' suffix, as appears the case for: \""
                                                         + species_trimmed + "\"" );
                    }
                    high_copy_base.add( species_trimmed );
                }
                else if ( species.startsWith( "*" ) ) {
                    if ( low_copy.contains( species_trimmed ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME,
                                                 "species/genome names can not appear with both '*' and '-' suffix, as appears the case for: \""
                                                         + species_trimmed + "\"" );
                    }
                    high_copy_target.add( species_trimmed );
                }
                else if ( species.startsWith( "-" ) ) {
                    if ( high_copy_base.contains( species_trimmed ) || high_copy_target.contains( species_trimmed ) ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME,
                                                 "species/genome names can not appear with both '+' or '*' and '-' suffix, as appears the case for: \""
                                                         + species_trimmed + "\"" );
                    }
                    low_copy.add( species_trimmed );
                }
                else if ( species.startsWith( "$D" ) ) {
                    try {
                        min_diff = Integer.parseInt( species.substring( 3 ) );
                    }
                    catch ( final NumberFormatException e ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME,
                                                 "could not parse integer value for minimal difference from: \""
                                                         + species.substring( 3 ) + "\"" );
                    }
                }
                else if ( species.startsWith( "$F" ) ) {
                    try {
                        factor = Double.parseDouble( species.substring( 3 ) );
                    }
                    catch ( final NumberFormatException e ) {
                        ForesterUtil.fatalError( surfacing.PRG_NAME,
                                                 "could not parse double value for factor from: \""
                                                         + species.substring( 3 ) + "\"" );
                    }
                }
                else if ( species.startsWith( "#" ) ) {
                    // Comment, ignore.
                }
                else {
                    ForesterUtil.fatalError( surfacing.PRG_NAME,
                                             "species/genome names in 'plus minus' file must begin with '*' (high copy target genome), '+' (high copy base genomes), '-' (low copy genomes), '$D=<integer>' minimal Difference (default is 1), '$F=<double>' factor (default is 1.0), double), or '#' (ignore) suffix, encountered: \""
                                                     + species + "\"" );
                }
                numbers.add( new Integer( min_diff + "" ) );
                numbers.add( new Double( factor + "" ) );
            }
        }
        else {
            ForesterUtil.fatalError( surfacing.PRG_NAME, "'plus minus' file [" + plus_minus_file + "] appears empty" );
        }
    }

    /*
     * species | protein id | n-terminal domain | c-terminal domain | n-terminal domain per domain E-value | c-terminal domain per domain E-value
     *
     *
     */
    static public StringBuffer proteinToDomainCombinations( final Protein protein,
                                                            final String protein_id,
                                                            final String separator ) {
        final StringBuffer sb = new StringBuffer();
        if ( protein.getSpecies() == null ) {
            throw new IllegalArgumentException( "species must not be null" );
        }
        if ( ForesterUtil.isEmpty( protein.getSpecies().getSpeciesId() ) ) {
            throw new IllegalArgumentException( "species id must not be empty" );
        }
        final List<Domain> domains = protein.getProteinDomains();
        if ( domains.size() > 1 ) {
            final Map<String, Integer> counts = new HashMap<String, Integer>();
            for( final Domain domain : domains ) {
                final String id = domain.getDomainId();
                if ( counts.containsKey( id ) ) {
                    counts.put( id, counts.get( id ) + 1 );
                }
                else {
                    counts.put( id, 1 );
                }
            }
            final Set<String> dcs = new HashSet<String>();
            for( int i = 1; i < domains.size(); ++i ) {
                for( int j = 0; j < i; ++j ) {
                    Domain domain_n = domains.get( i );
                    Domain domain_c = domains.get( j );
                    if ( domain_n.getFrom() > domain_c.getFrom() ) {
                        domain_n = domains.get( j );
                        domain_c = domains.get( i );
                    }
                    final String dc = domain_n.getDomainId() + domain_c.getDomainId();
                    if ( !dcs.contains( dc ) ) {
                        dcs.add( dc );
                        sb.append( protein.getSpecies() );
                        sb.append( separator );
                        sb.append( protein_id );
                        sb.append( separator );
                        sb.append( domain_n.getDomainId() );
                        sb.append( separator );
                        sb.append( domain_c.getDomainId() );
                        sb.append( separator );
                        sb.append( domain_n.getPerDomainEvalue() );
                        sb.append( separator );
                        sb.append( domain_c.getPerDomainEvalue() );
                        sb.append( separator );
                        sb.append( counts.get( domain_n.getDomainId() ) );
                        sb.append( separator );
                        sb.append( counts.get( domain_c.getDomainId() ) );
                        sb.append( ForesterUtil.LINE_SEPARATOR );
                    }
                }
            }
        }
        else if ( domains.size() == 1 ) {
            sb.append( protein.getSpecies() );
            sb.append( separator );
            sb.append( protein_id );
            sb.append( separator );
            sb.append( domains.get( 0 ).getDomainId() );
            sb.append( separator );
            sb.append( separator );
            sb.append( domains.get( 0 ).getPerDomainEvalue() );
            sb.append( separator );
            sb.append( separator );
            sb.append( 1 );
            sb.append( separator );
            sb.append( ForesterUtil.LINE_SEPARATOR );
        }
        else {
            sb.append( protein.getSpecies() );
            sb.append( separator );
            sb.append( protein_id );
            sb.append( separator );
            sb.append( separator );
            sb.append( separator );
            sb.append( separator );
            sb.append( separator );
            sb.append( separator );
            sb.append( ForesterUtil.LINE_SEPARATOR );
        }
        return sb;
    }

    public static List<Domain> sortDomainsWithAscendingConfidenceValues( final Protein protein ) {
        final List<Domain> domains = new ArrayList<Domain>();
        for( final Domain d : protein.getProteinDomains() ) {
            domains.add( d );
        }
        Collections.sort( domains, SurfacingUtil.ASCENDING_CONFIDENCE_VALUE_ORDER );
        return domains;
    }

    public static int storeDomainArchitectures( final String genome,
                                                final SortedMap<String, Set<String>> domain_architecutures,
                                                final List<Protein> protein_list,
                                                final Map<String, Integer> distinct_domain_architecuture_counts ) {
        final Set<String> da = new HashSet<String>();
        domain_architecutures.put( genome, da );
        for( final Protein protein : protein_list ) {
            final String da_str = ( ( BasicProtein ) protein ).toDomainArchitectureString( "~", 3, "=" );
            if ( !da.contains( da_str ) ) {
                if ( !distinct_domain_architecuture_counts.containsKey( da_str ) ) {
                    distinct_domain_architecuture_counts.put( da_str, 1 );
                }
                else {
                    distinct_domain_architecuture_counts.put( da_str,
                                                              distinct_domain_architecuture_counts.get( da_str ) + 1 );
                }
                da.add( da_str );
            }
        }
        return da.size();
    }

    public static void writeAllDomainsChangedOnAllSubtrees( final Phylogeny p,
                                                            final boolean get_gains,
                                                            final String outdir,
                                                            final String suffix_for_filename )
            throws IOException {
        CharacterStateMatrix.GainLossStates state = CharacterStateMatrix.GainLossStates.GAIN;
        if ( !get_gains ) {
            state = CharacterStateMatrix.GainLossStates.LOSS;
        }
        final File base_dir = createBaseDirForPerNodeDomainFiles( surfacing.BASE_DIRECTORY_PER_SUBTREE_DOMAIN_GAIN_LOSS_FILES,
                                                                  false,
                                                                  state,
                                                                  outdir );
        for( final PhylogenyNodeIterator it = p.iteratorPostorder(); it.hasNext(); ) {
            final PhylogenyNode node = it.next();
            if ( !node.isExternal() ) {
                final SortedSet<String> domains = collectAllDomainsChangedOnSubtree( node, get_gains );
                if ( domains.size() > 0 ) {
                    final Writer writer = ForesterUtil.createBufferedWriter( base_dir + ForesterUtil.FILE_SEPARATOR
                            + node.getName() + suffix_for_filename );
                    for( final String domain : domains ) {
                        writer.write( domain );
                        writer.write( ForesterUtil.LINE_SEPARATOR );
                    }
                    writer.close();
                }
            }
        }
    }

    public static void writeBinaryDomainCombinationsFileForGraphAnalysis( final String[][] input_file_properties,
                                                                          final File output_dir,
                                                                          final GenomeWideCombinableDomains gwcd,
                                                                          final int i,
                                                                          final GenomeWideCombinableDomainsSortOrder dc_sort_order ) {
        File dc_outfile_dot = new File( input_file_properties[ i ][ 1 ]
                + surfacing.DOMAIN_COMBINITONS_OUTPUTFILE_SUFFIX_FOR_GRAPH_ANALYSIS );
        if ( output_dir != null ) {
            dc_outfile_dot = new File( output_dir + ForesterUtil.FILE_SEPARATOR + dc_outfile_dot );
        }
        checkForOutputFileWriteability( dc_outfile_dot );
        final SortedSet<BinaryDomainCombination> binary_combinations = createSetOfAllBinaryDomainCombinationsPerGenome( gwcd );
        try {
            final BufferedWriter out_dot = new BufferedWriter( new FileWriter( dc_outfile_dot ) );
            for( final BinaryDomainCombination bdc : binary_combinations ) {
                out_dot.write( bdc.toGraphDescribingLanguage( BinaryDomainCombination.OutputFormat.DOT, null, null )
                        .toString() );
                out_dot.write( SurfacingConstants.NL );
            }
            out_dot.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        if ( input_file_properties[ i ].length == 3 ) {
            ForesterUtil
                    .programMessage( surfacing.PRG_NAME,
                                     "Wrote binary domain combination for \"" + input_file_properties[ i ][ 0 ] + "\" ("
                                             + input_file_properties[ i ][ 1 ] + ", " + input_file_properties[ i ][ 2 ]
                                             + ") to: \"" + dc_outfile_dot + "\"" );
        }
        else {
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote binary domain combination for \"" + input_file_properties[ i ][ 0 ]
                                                 + "\" (" + input_file_properties[ i ][ 1 ] + ") to: \""
                                                 + dc_outfile_dot + "\"" );
        }
    }

    public static void writeBinaryStatesMatrixAsListToFile( final CharacterStateMatrix<CharacterStateMatrix.GainLossStates> matrix,
                                                            final CharacterStateMatrix.GainLossStates state,
                                                            final String filename,
                                                            final String indentifier_characters_separator,
                                                            final String character_separator,
                                                            final Map<String, String> descriptions ) {
        final File outfile = new File( filename );
        checkForOutputFileWriteability( outfile );
        final SortedSet<String> sorted_ids = new TreeSet<String>();
        for( int i = 0; i < matrix.getNumberOfIdentifiers(); ++i ) {
            sorted_ids.add( matrix.getIdentifier( i ) );
        }
        try {
            final BufferedWriter out = new BufferedWriter( new FileWriter( outfile ) );
            for( final String id : sorted_ids ) {
                out.write( indentifier_characters_separator );
                out.write( "#" + id );
                out.write( indentifier_characters_separator );
                for( int c = 0; c < matrix.getNumberOfCharacters(); ++c ) {
                    // Not nice:
                    // using null to indicate either UNCHANGED_PRESENT or GAIN.
                    if ( ( matrix.getState( id, c ) == state ) || ( ( state == null )
                            && ( ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.GAIN ) || ( matrix
                                    .getState( id,
                                               c ) == CharacterStateMatrix.GainLossStates.UNCHANGED_PRESENT ) ) ) ) {
                        out.write( matrix.getCharacter( c ) );
                        if ( ( descriptions != null ) && !descriptions.isEmpty()
                                && descriptions.containsKey( matrix.getCharacter( c ) ) ) {
                            out.write( "\t" );
                            out.write( descriptions.get( matrix.getCharacter( c ) ) );
                        }
                        out.write( character_separator );
                    }
                }
            }
            out.flush();
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote characters list: \"" + filename + "\"" );
    }

    public static void writeBinaryStatesMatrixAsListToFileForBinaryCombinationsForGraphAnalysis( final CharacterStateMatrix<CharacterStateMatrix.GainLossStates> matrix,
                                                                                                 final CharacterStateMatrix.GainLossStates state,
                                                                                                 final String filename,
                                                                                                 final String indentifier_characters_separator,
                                                                                                 final String character_separator,
                                                                                                 final BinaryDomainCombination.OutputFormat bc_output_format ) {
        final File outfile = new File( filename );
        checkForOutputFileWriteability( outfile );
        final SortedSet<String> sorted_ids = new TreeSet<String>();
        for( int i = 0; i < matrix.getNumberOfIdentifiers(); ++i ) {
            sorted_ids.add( matrix.getIdentifier( i ) );
        }
        try {
            final BufferedWriter out = new BufferedWriter( new FileWriter( outfile ) );
            for( final String id : sorted_ids ) {
                out.write( indentifier_characters_separator );
                out.write( "#" + id );
                out.write( indentifier_characters_separator );
                for( int c = 0; c < matrix.getNumberOfCharacters(); ++c ) {
                    // Not nice:
                    // using null to indicate either UNCHANGED_PRESENT or GAIN.
                    if ( ( matrix.getState( id, c ) == state ) || ( ( state == null )
                            && ( ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.GAIN ) || ( matrix
                                    .getState( id,
                                               c ) == CharacterStateMatrix.GainLossStates.UNCHANGED_PRESENT ) ) ) ) {
                        BinaryDomainCombination bdc = null;
                        try {
                            bdc = BasicBinaryDomainCombination.obtainInstance( matrix.getCharacter( c ) );
                        }
                        catch ( final Exception e ) {
                            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
                        }
                        out.write( bdc.toGraphDescribingLanguage( bc_output_format, null, null ).toString() );
                        out.write( character_separator );
                    }
                }
            }
            out.flush();
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote characters list: \"" + filename + "\"" );
    }

    public static void writeBinaryStatesMatrixToList( final Map<String, List<GoId>> domain_id_to_go_ids_map,
                                                      final Map<GoId, GoTerm> go_id_to_term_map,
                                                      final GoNameSpace go_namespace_limit,
                                                      final boolean domain_combinations,
                                                      final CharacterStateMatrix<CharacterStateMatrix.GainLossStates> matrix,
                                                      final CharacterStateMatrix.GainLossStates state,
                                                      final String filename,
                                                      final String indentifier_characters_separator,
                                                      final String character_separator,
                                                      final String title_for_html,
                                                      final String prefix_for_html,
                                                      final Map<String, Set<String>>[] domain_id_to_secondary_features_maps,
                                                      final SortedSet<String> all_pfams_encountered,
                                                      final SortedSet<String> pfams_gained_or_lost,
                                                      final String suffix_for_per_node_events_file,
                                                      final Map<String, Integer> tax_code_to_id_map ) {
        if ( ( go_namespace_limit != null ) && ( ( go_id_to_term_map == null ) || ( go_id_to_term_map.size() < 1 ) ) ) {
            throw new IllegalArgumentException( "attempt to use GO namespace limit without a GO-id to term map" );
        }
        else if ( ( ( domain_id_to_go_ids_map == null ) || ( domain_id_to_go_ids_map.size() < 1 ) ) ) {
            throw new IllegalArgumentException( "attempt to output detailed HTML without a Pfam to GO map" );
        }
        else if ( ( ( go_id_to_term_map == null ) || ( go_id_to_term_map.size() < 1 ) ) ) {
            throw new IllegalArgumentException( "attempt to output detailed HTML without a GO-id to term map" );
        }
        final File outfile = new File( filename );
        checkForOutputFileWriteability( outfile );
        final SortedSet<String> sorted_ids = new TreeSet<String>();
        for( int i = 0; i < matrix.getNumberOfIdentifiers(); ++i ) {
            sorted_ids.add( matrix.getIdentifier( i ) );
        }
        try {
            final Writer out = new BufferedWriter( new FileWriter( outfile ) );
            final File per_node_go_mapped_domain_gain_loss_files_base_dir = createBaseDirForPerNodeDomainFiles( surfacing.BASE_DIRECTORY_PER_NODE_DOMAIN_GAIN_LOSS_FILES,
                                                                                                                domain_combinations,
                                                                                                                state,
                                                                                                                filename );
            Writer per_node_go_mapped_domain_gain_loss_outfile_writer = null;
            File per_node_go_mapped_domain_gain_loss_outfile = null;
            int per_node_counter = 0;
            out.write( "<html>" );
            out.write( SurfacingConstants.NL );
            writeHtmlHead( out, title_for_html );
            out.write( SurfacingConstants.NL );
            out.write( "<body>" );
            out.write( SurfacingConstants.NL );
            out.write( "<h1>" );
            out.write( SurfacingConstants.NL );
            out.write( title_for_html );
            out.write( SurfacingConstants.NL );
            out.write( "</h1>" );
            out.write( SurfacingConstants.NL );
            out.write( "<table>" );
            out.write( SurfacingConstants.NL );
            for( final String id : sorted_ids ) {
                final Matcher matcher = PATTERN_SP_STYLE_TAXONOMY.matcher( id );
                if ( matcher.matches() ) {
                    continue;
                }
                out.write( "<tr>" );
                out.write( "<td>" );
                out.write( "<a href=\"#" + id + "\">" + id + "</a>" );
                out.write( "</td>" );
                out.write( "</tr>" );
                out.write( SurfacingConstants.NL );
            }
            out.write( "</table>" );
            out.write( SurfacingConstants.NL );
            for( final String id : sorted_ids ) {
                final Matcher matcher = PATTERN_SP_STYLE_TAXONOMY.matcher( id );
                if ( matcher.matches() ) {
                    continue;
                }
                out.write( SurfacingConstants.NL );
                out.write( "<h2>" );
                out.write( "<a name=\"" + id + "\">" + id + "</a>" );
                writeTaxonomyLinks( out, id, tax_code_to_id_map );
                out.write( "</h2>" );
                out.write( SurfacingConstants.NL );
                out.write( "<table>" );
                out.write( SurfacingConstants.NL );
                out.write( "<tr>" );
                out.write( "<td><b>" );
                out.write( "Pfam domain(s)" );
                out.write( "</b></td><td><b>" );
                out.write( "GO term acc" );
                out.write( "</b></td><td><b>" );
                out.write( "GO term" );
                out.write( "</b></td><td><b>" );
                out.write( "GO namespace" );
                out.write( "</b></td>" );
                out.write( "</tr>" );
                out.write( SurfacingConstants.NL );
                out.write( "</tr>" );
                out.write( SurfacingConstants.NL );
                per_node_counter = 0;
                if ( matrix.getNumberOfCharacters() > 0 ) {
                    per_node_go_mapped_domain_gain_loss_outfile = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                            + ForesterUtil.FILE_SEPARATOR + id + suffix_for_per_node_events_file );
                    SurfacingUtil.checkForOutputFileWriteability( per_node_go_mapped_domain_gain_loss_outfile );
                    per_node_go_mapped_domain_gain_loss_outfile_writer = ForesterUtil
                            .createBufferedWriter( per_node_go_mapped_domain_gain_loss_outfile );
                }
                else {
                    per_node_go_mapped_domain_gain_loss_outfile = null;
                    per_node_go_mapped_domain_gain_loss_outfile_writer = null;
                }
                for( int c = 0; c < matrix.getNumberOfCharacters(); ++c ) {
                    // Not nice:
                    // using null to indicate either UNCHANGED_PRESENT or GAIN.
                    if ( ( matrix.getState( id, c ) == state ) || ( ( state == null )
                            && ( ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.UNCHANGED_PRESENT )
                                    || ( matrix.getState( id, c ) == CharacterStateMatrix.GainLossStates.GAIN ) ) ) ) {
                        final String character = matrix.getCharacter( c );
                        String domain_0 = "";
                        String domain_1 = "";
                        if ( character.indexOf( BinaryDomainCombination.SEPARATOR ) > 0 ) {
                            final String[] s = character.split( BinaryDomainCombination.SEPARATOR );
                            if ( s.length != 2 ) {
                                throw new AssertionError( "this should not have happened: unexpected format for domain combination: ["
                                        + character + "]" );
                            }
                            domain_0 = s[ 0 ];
                            domain_1 = s[ 1 ];
                        }
                        else {
                            domain_0 = character;
                        }
                        writeDomainData( domain_id_to_go_ids_map,
                                         go_id_to_term_map,
                                         go_namespace_limit,
                                         out,
                                         domain_0,
                                         domain_1,
                                         prefix_for_html,
                                         character_separator,
                                         domain_id_to_secondary_features_maps,
                                         null );
                        all_pfams_encountered.add( domain_0 );
                        if ( pfams_gained_or_lost != null ) {
                            pfams_gained_or_lost.add( domain_0 );
                        }
                        if ( !ForesterUtil.isEmpty( domain_1 ) ) {
                            all_pfams_encountered.add( domain_1 );
                            if ( pfams_gained_or_lost != null ) {
                                pfams_gained_or_lost.add( domain_1 );
                            }
                        }
                        if ( per_node_go_mapped_domain_gain_loss_outfile_writer != null ) {
                            writeDomainsToIndividualFilePerTreeNode( per_node_go_mapped_domain_gain_loss_outfile_writer,
                                                                     domain_0,
                                                                     domain_1 );
                            per_node_counter++;
                        }
                    }
                }
                if ( per_node_go_mapped_domain_gain_loss_outfile_writer != null ) {
                    per_node_go_mapped_domain_gain_loss_outfile_writer.close();
                    if ( per_node_counter < 1 ) {
                        per_node_go_mapped_domain_gain_loss_outfile.delete();
                    }
                    per_node_counter = 0;
                }
                out.write( "</table>" );
                out.write( SurfacingConstants.NL );
                out.write( "<hr>" );
                out.write( SurfacingConstants.NL );
            } // for( final String id : sorted_ids ) {
            out.write( "</body>" );
            out.write( SurfacingConstants.NL );
            out.write( "</html>" );
            out.write( SurfacingConstants.NL );
            out.flush();
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote characters detailed HTML list: \"" + filename + "\"" );
    }

    public static void writeDomainCombinationsCountsFile( final String[][] input_file_properties,
                                                          final File output_dir,
                                                          final Writer per_genome_domain_promiscuity_statistics_writer,
                                                          final GenomeWideCombinableDomains gwcd,
                                                          final int i,
                                                          final GenomeWideCombinableDomains.GenomeWideCombinableDomainsSortOrder dc_sort_order ) {
        File dc_outfile = new File( input_file_properties[ i ][ 1 ]
                + surfacing.DOMAIN_COMBINITON_COUNTS_OUTPUTFILE_SUFFIX );
        if ( output_dir != null ) {
            dc_outfile = new File( output_dir + ForesterUtil.FILE_SEPARATOR + dc_outfile );
        }
        checkForOutputFileWriteability( dc_outfile );
        try {
            final BufferedWriter out = new BufferedWriter( new FileWriter( dc_outfile ) );
            out.write( gwcd.toStringBuilder( dc_sort_order ).toString() );
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        final DescriptiveStatistics stats = gwcd.getPerGenomeDomainPromiscuityStatistics();
        try {
            per_genome_domain_promiscuity_statistics_writer.write( input_file_properties[ i ][ 1 ] + "\t" );
            per_genome_domain_promiscuity_statistics_writer
                    .write( FORMATTER_3.format( stats.arithmeticMean() ) + "\t" );
            if ( stats.getN() < 2 ) {
                per_genome_domain_promiscuity_statistics_writer.write( "n/a" + "\t" );
            }
            else {
                per_genome_domain_promiscuity_statistics_writer
                        .write( FORMATTER_3.format( stats.sampleStandardDeviation() ) + "\t" );
            }
            per_genome_domain_promiscuity_statistics_writer.write( FORMATTER_3.format( stats.median() ) + "\t" );
            per_genome_domain_promiscuity_statistics_writer.write( ( int ) stats.getMin() + "\t" );
            per_genome_domain_promiscuity_statistics_writer.write( ( int ) stats.getMax() + "\t" );
            per_genome_domain_promiscuity_statistics_writer.write( stats.getN() + "\t" );
            final SortedSet<String> mpds = gwcd.getMostPromiscuosDomain();
            for( final String mpd : mpds ) {
                per_genome_domain_promiscuity_statistics_writer.write( mpd + " " );
            }
            per_genome_domain_promiscuity_statistics_writer.write( ForesterUtil.LINE_SEPARATOR );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        if ( input_file_properties[ i ].length == 3 ) {
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote domain combination counts for \"" + input_file_properties[ i ][ 0 ]
                                                 + "\" (" + input_file_properties[ i ][ 1 ] + ", "
                                                 + input_file_properties[ i ][ 2 ] + ") to: \"" + dc_outfile + "\"" );
        }
        else {
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote domain combination counts for \"" + input_file_properties[ i ][ 0 ]
                                                 + "\" (" + input_file_properties[ i ][ 1 ] + ") to: \"" + dc_outfile
                                                 + "\"" );
        }
    }

    public static void writeDomainSimilaritiesToFile( final StringBuilder html_desc,
                                                      final StringBuilder html_title,
                                                      final Writer simple_tab_writer,
                                                      final Writer single_writer,
                                                      Map<Character, Writer> split_writers,
                                                      final SortedSet<DomainSimilarity> similarities,
                                                      final boolean treat_as_binary,
                                                      final List<Species> species_order,
                                                      final DomainSimilarity.PRINT_OPTION print_option,
                                                      final DomainSimilarity.DomainSimilarityScoring scoring,
                                                      final boolean verbose,
                                                      final Map<String, Integer> tax_code_to_id_map,
                                                      final Phylogeny phy,
                                                      final Set<String> pos_filter_doms )
            throws IOException {
        if ( ( single_writer != null ) && ( ( split_writers == null ) || split_writers.isEmpty() ) ) {
            split_writers = new HashMap<Character, Writer>();
            split_writers.put( '_', single_writer );
        }
        switch ( print_option ) {
            case SIMPLE_TAB_DELIMITED:
                break;
            case HTML:
                for( final Character key : split_writers.keySet() ) {
                    final Writer w = split_writers.get( key );
                    w.write( "<html>" );
                    w.write( SurfacingConstants.NL );
                    if ( key != '_' ) {
                        writeHtmlHead( w, "DC analysis (" + html_title + ") " + key.toString().toUpperCase() );
                    }
                    else {
                        writeHtmlHead( w, "DC analysis (" + html_title + ")" );
                    }
                    w.write( SurfacingConstants.NL );
                    w.write( "<body>" );
                    w.write( SurfacingConstants.NL );
                    w.write( html_desc.toString() );
                    w.write( SurfacingConstants.NL );
                    w.write( "<hr>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "<br>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "<table>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "<tr><td><b>Domains:</b></td></tr>" );
                    w.write( SurfacingConstants.NL );
                }
                break;
        }
        //
        for( final DomainSimilarity similarity : similarities ) {
            if ( ( species_order != null ) && !species_order.isEmpty() ) {
                ( similarity ).setSpeciesOrder( species_order );
            }
            if ( single_writer != null ) {
                if ( !ForesterUtil.isEmpty( pos_filter_doms )
                        && pos_filter_doms.contains( similarity.getDomainId() ) ) {
                    single_writer.write( "<tr><td><b><a href=\"#" + similarity.getDomainId()
                            + "\"><span style=\"color:#00ff00\">" + similarity.getDomainId()
                            + "</span></a></b></td></tr>" );
                }
                else {
                    single_writer.write( "<tr><td><b><a href=\"#" + similarity.getDomainId() + "\">"
                            + similarity.getDomainId() + "</a></b></td></tr>" );
                }
                single_writer.write( SurfacingConstants.NL );
            }
            else {
                Writer local_writer = split_writers
                        .get( ( similarity.getDomainId().charAt( 0 ) + "" ).toLowerCase().charAt( 0 ) );
                if ( local_writer == null ) {
                    local_writer = split_writers.get( '0' );
                }
                if ( !ForesterUtil.isEmpty( pos_filter_doms )
                        && pos_filter_doms.contains( similarity.getDomainId() ) ) {
                    local_writer.write( "<tr><td><b><a href=\"#" + similarity.getDomainId()
                            + "\"><span style=\"color:#00ff00\">" + similarity.getDomainId()
                            + "</span></a></b></td></tr>" );
                }
                else {
                    local_writer.write( "<tr><td><b><a href=\"#" + similarity.getDomainId() + "\">"
                            + similarity.getDomainId() + "</a></b></td></tr>" );
                }
                local_writer.write( SurfacingConstants.NL );
            }
        }
        for( final Writer w : split_writers.values() ) {
            w.write( "</table>" );
            w.write( SurfacingConstants.NL );
            w.write( "<hr>" );
            w.write( SurfacingConstants.NL );
            //
            w.write( "<table>" );
            w.write( SurfacingConstants.NL );
            w.write( "<tr><td><b>" );
            w.write( "Species group colors:" );
            w.write( "</b></td></tr>" );
            w.write( SurfacingConstants.NL );
            writeColorLabels( "Deuterostomia", TaxonomyColors.DEUTEROSTOMIA_COLOR, w );
            writeColorLabels( "Protostomia", TaxonomyColors.PROTOSTOMIA_COLOR, w );
            writeColorLabels( "Cnidaria", TaxonomyColors.CNIDARIA_COLOR, w );
            writeColorLabels( "Placozoa", TaxonomyColors.PLACOZOA_COLOR, w );
            writeColorLabels( "Ctenophora (comb jellies)", TaxonomyColors.CTENOPHORA_COLOR, w );
            writeColorLabels( "Porifera (sponges)", TaxonomyColors.PORIFERA_COLOR, w );
            writeColorLabels( "Choanoflagellida", TaxonomyColors.CHOANOFLAGELLIDA, w );
            writeColorLabels( "Ichthyosporea & Filasterea", TaxonomyColors.ICHTHYOSPOREA_AND_FILASTEREA, w );
            writeColorLabels( "Dikarya (Ascomycota & Basidiomycota, so-called \"higher fungi\")",
                              TaxonomyColors.DIKARYA_COLOR,
                              w );
            writeColorLabels( "other Fungi", TaxonomyColors.OTHER_FUNGI_COLOR, w );
            writeColorLabels( "Nucleariidae and Fonticula group",
                              TaxonomyColors.NUCLEARIIDAE_AND_FONTICULA_GROUP_COLOR,
                              w );
            writeColorLabels( "Amoebozoa", TaxonomyColors.AMOEBOZOA_COLOR, w );
            writeColorLabels( "Embryophyta (plants)", TaxonomyColors.EMBRYOPHYTA_COLOR, w );
            writeColorLabels( "Chlorophyta (green algae)", TaxonomyColors.CHLOROPHYTA_COLOR, w );
            writeColorLabels( "Rhodophyta (red algae)", TaxonomyColors.RHODOPHYTA_COLOR, w );
            writeColorLabels( "Glaucocystophyce (Glaucophyta)", TaxonomyColors.GLAUCOPHYTA_COLOR, w );
            writeColorLabels( "Hacrobia (Cryptophyta & Haptophyceae & Centroheliozoa)",
                              TaxonomyColors.HACROBIA_COLOR,
                              w );
            writeColorLabels( "Stramenopiles (Chromophyta, heterokonts)", TaxonomyColors.STRAMENOPILES_COLOR, w );
            writeColorLabels( "Alveolata", TaxonomyColors.ALVEOLATA_COLOR, w );
            writeColorLabels( "Rhizaria", TaxonomyColors.RHIZARIA_COLOR, w );
            writeColorLabels( "Excavata", TaxonomyColors.EXCAVATA_COLOR, w );
            writeColorLabels( "Apusozoa", TaxonomyColors.APUSOZOA_COLOR, w );
            writeColorLabels( "Archaea", TaxonomyColors.ARCHAEA_COLOR, w );
            writeColorLabels( "Bacteria", TaxonomyColors.BACTERIA_COLOR, w );
            w.write( "</table>" );
            w.write( SurfacingConstants.NL );
            //
            w.write( "<hr>" );
            w.write( SurfacingConstants.NL );
            w.write( "<table>" );
            w.write( SurfacingConstants.NL );
        }
        //
        for( final DomainSimilarity similarity : similarities ) {
            if ( ( species_order != null ) && !species_order.isEmpty() ) {
                ( similarity ).setSpeciesOrder( species_order );
            }
            if ( simple_tab_writer != null ) {
                simple_tab_writer.write( similarity
                        .toStringBuffer( PRINT_OPTION.SIMPLE_TAB_DELIMITED, tax_code_to_id_map, null ).toString() );
            }
            if ( single_writer != null ) {
                single_writer.write( similarity.toStringBuffer( print_option, tax_code_to_id_map, phy ).toString() );
                single_writer.write( SurfacingConstants.NL );
            }
            else {
                Writer local_writer = split_writers
                        .get( ( similarity.getDomainId().charAt( 0 ) + "" ).toLowerCase().charAt( 0 ) );
                if ( local_writer == null ) {
                    local_writer = split_writers.get( '0' );
                }
                local_writer.write( similarity.toStringBuffer( print_option, tax_code_to_id_map, phy ).toString() );
                local_writer.write( SurfacingConstants.NL );
            }
        }
        switch ( print_option ) {
            case HTML:
                for( final Writer w : split_writers.values() ) {
                    w.write( SurfacingConstants.NL );
                    w.write( "</table>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "</font>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "</body>" );
                    w.write( SurfacingConstants.NL );
                    w.write( "</html>" );
                    w.write( SurfacingConstants.NL );
                }
                break;
            default:
                break;
        }
        for( final Writer w : split_writers.values() ) {
            w.close();
        }
    }

    public static void writeHtmlHead( final Writer w, final String title ) throws IOException {
        w.write( SurfacingConstants.NL );
        w.write( "<head>" );
        w.write( "<title>" );
        w.write( title );
        w.write( "</title>" );
        w.write( SurfacingConstants.NL );
        w.write( "<style>" );
        w.write( SurfacingConstants.NL );
        w.write( "a:visited { color : #000066; text-decoration : none; }" );
        w.write( SurfacingConstants.NL );
        w.write( "a:link { color : #000066; text-decoration : none; }" );
        w.write( SurfacingConstants.NL );
        w.write( "a:active { color : ##000066; text-decoration : none; }" );
        w.write( SurfacingConstants.NL );
        w.write( "a:hover { color : #FFFFFF; background-color : #000000; text-decoration : none; }" );
        w.write( SurfacingConstants.NL );
        //
        w.write( "a.pl:visited { color : #505050; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.pl:link { color : #505050; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.pl:active { color : #505050; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.pl:hover { color : #FFFFFF; background-color : #000000; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        //
        w.write( "a.ps:visited { color : #707070; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.ps:link { color : #707070; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.ps:active { color : #707070; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        w.write( "a.ps:hover { color : #FFFFFF; background-color : #000000; text-decoration : none; font-size: 7px;}" );
        w.write( SurfacingConstants.NL );
        //
        w.write( "td { text-align: left; vertical-align: top; font-family: Verdana, Arial, Helvetica; font-size: 8pt}" );
        w.write( SurfacingConstants.NL );
        w.write( "h1 { color : #0000FF; font-family: Verdana, Arial, Helvetica; font-size: 18pt; font-weight: bold }" );
        w.write( SurfacingConstants.NL );
        w.write( "h2 { color : #0000FF; font-family: Verdana, Arial, Helvetica; font-size: 16pt; font-weight: bold }" );
        w.write( SurfacingConstants.NL );
        w.write( "</style>" );
        w.write( SurfacingConstants.NL );
        w.write( "</head>" );
        w.write( SurfacingConstants.NL );
    }

    public static void writeMatrixToFile( final CharacterStateMatrix<?> matrix,
                                          final String filename,
                                          final Format format ) {
        final File outfile = new File( filename );
        checkForOutputFileWriteability( outfile );
        try {
            final BufferedWriter out = new BufferedWriter( new FileWriter( outfile ) );
            matrix.toWriter( out, format );
            out.flush();
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote matrix: \"" + filename + "\"" );
    }

    public static void writeMatrixToFile( final File matrix_outfile, final List<DistanceMatrix> matrices ) {
        checkForOutputFileWriteability( matrix_outfile );
        try {
            final BufferedWriter out = new BufferedWriter( new FileWriter( matrix_outfile ) );
            for( final DistanceMatrix distance_matrix : matrices ) {
                out.write( distance_matrix.toStringBuffer( DistanceMatrix.Format.PHYLIP ).toString() );
                out.write( ForesterUtil.LINE_SEPARATOR );
                out.flush();
            }
            out.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote distance matrices to \"" + matrix_outfile + "\"" );
    }

    public static void writePhylogenyToFile( final Phylogeny phylogeny, final String filename ) {
        final PhylogenyWriter writer = new PhylogenyWriter();
        try {
            writer.toPhyloXML( new File( filename ), phylogeny, 1 );
        }
        catch ( final IOException e ) {
            ForesterUtil.printWarningMessage( surfacing.PRG_NAME,
                                              "failed to write phylogeny to \"" + filename + "\": " + e );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote phylogeny to \"" + filename + "\"" );
    }

    public static void writePresentToNexus( final File output_file,
                                            final File positive_filter_file,
                                            final SortedSet<String> filter,
                                            final List<GenomeWideCombinableDomains> gwcd_list ) {
        try {
            writeMatrixToFile( DomainParsimonyCalculator
                    .createMatrixOfDomainPresenceOrAbsence( gwcd_list, positive_filter_file == null ? null : filter ),
                               output_file + surfacing.DOMAINS_PRESENT_NEXUS,
                               Format.NEXUS_BINARY );
            writeMatrixToFile( DomainParsimonyCalculator
                    .createMatrixOfBinaryDomainCombinationPresenceOrAbsence( gwcd_list ),
                               output_file + surfacing.BDC_PRESENT_NEXUS,
                               Format.NEXUS_BINARY );
        }
        catch ( final Exception e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
        }
    }

    public static void writeProteinListsForAllSpecies( final File output_dir,
                                                       final SortedMap<Species, List<Protein>> protein_lists_per_species,
                                                       final List<GenomeWideCombinableDomains> gwcd_list,
                                                       final double domain_e_cutoff,
                                                       final Set<String> pos_filter_doms ) {
        final SortedSet<String> all_domains = new TreeSet<String>();
        for( final GenomeWideCombinableDomains gwcd : gwcd_list ) {
            all_domains.addAll( gwcd.getAllDomainIds() );
        }
        for( final String domain : all_domains ) {
            if ( !ForesterUtil.isEmpty( pos_filter_doms ) && !pos_filter_doms.contains( domain ) ) {
                continue;
            }
            final File out = new File( output_dir + ForesterUtil.FILE_SEPARATOR + domain
                    + surfacing.SEQ_EXTRACT_SUFFIX );
            checkForOutputFileWriteability( out );
            try {
                final Writer proteins_file_writer = new BufferedWriter( new FileWriter( out ) );
                extractProteinNames( protein_lists_per_species,
                                     domain,
                                     proteins_file_writer,
                                     "\t",
                                     surfacing.LIMIT_SPEC_FOR_PROT_EX,
                                     domain_e_cutoff );
                proteins_file_writer.close();
            }
            catch ( final IOException e ) {
                ForesterUtil.fatalError( surfacing.PRG_NAME, e.getLocalizedMessage() );
            }
            ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote proteins list to \"" + out + "\"" );
        }
    }

    public static void writeTaxonomyLinks( final Writer writer,
                                           final String species,
                                           final Map<String, Integer> tax_code_to_id_map )
            throws IOException {
        if ( ( species.length() > 1 ) && ( species.indexOf( '_' ) < 1 ) ) {
            writer.write( " [" );
            if ( ( tax_code_to_id_map != null ) && tax_code_to_id_map.containsKey( species ) ) {
                writer.write( "<a href=\"" + SurfacingConstants.UNIPROT_TAXONOMY_ID_LINK
                        + tax_code_to_id_map.get( species ) + "\" target=\"taxonomy_window\">uniprot</a>" );
            }
            else {
                writer.write( "<a href=\"" + SurfacingConstants.EOL_LINK + species
                        + "\" target=\"taxonomy_window\">eol</a>" );
                writer.write( "|" );
                writer.write( "<a href=\"" + SurfacingConstants.GOOGLE_SCHOLAR_SEARCH + species
                        + "\" target=\"taxonomy_window\">scholar</a>" );
                writer.write( "|" );
                writer.write( "<a href=\"" + SurfacingConstants.GOOGLE_WEB_SEARCH_LINK + species
                        + "\" target=\"taxonomy_window\">google</a>" );
            }
            writer.write( "]" );
        }
    }

    private final static void addToCountMap( final Map<String, Integer> map, final String s ) {
        if ( map.containsKey( s ) ) {
            map.put( s, map.get( s ) + 1 );
        }
        else {
            map.put( s, 1 );
        }
    }

    private static void calculateIndependentDomainCombinationGains( final Phylogeny local_phylogeny_l,
                                                                    final String outfilename_for_counts,
                                                                    final String outfilename_for_dc,
                                                                    final String outfilename_for_dc_for_go_mapping,
                                                                    final String outfilename_for_dc_for_go_mapping_unique,
                                                                    final String outfilename_for_rank_counts,
                                                                    final String outfilename_for_ancestor_species_counts,
                                                                    final String outfilename_for_protein_stats,
                                                                    final Map<String, DescriptiveStatistics> protein_length_stats_by_dc,
                                                                    final Map<String, DescriptiveStatistics> domain_number_stats_by_dc,
                                                                    final Map<String, DescriptiveStatistics> domain_length_stats_by_domain ) {
        try {
            //
            //            if ( protein_length_stats_by_dc != null ) {
            //                for( final Entry<?, DescriptiveStatistics> entry : protein_length_stats_by_dc.entrySet() ) {
            //                    System.out.print( entry.getKey().toString() );
            //                    System.out.print( ": " );
            //                    double[] a = entry.getValue().getDataAsDoubleArray();
            //                    for( int i = 0; i < a.length; i++ ) {
            //                        System.out.print( a[ i ] + " " );
            //                    }
            //                    System.out.println();
            //                }
            //            }
            //            if ( domain_number_stats_by_dc != null ) {
            //                for( final Entry<?, DescriptiveStatistics> entry : domain_number_stats_by_dc.entrySet() ) {
            //                    System.out.print( entry.getKey().toString() );
            //                    System.out.print( ": " );
            //                    double[] a = entry.getValue().getDataAsDoubleArray();
            //                    for( int i = 0; i < a.length; i++ ) {
            //                        System.out.print( a[ i ] + " " );
            //                    }
            //                    System.out.println();
            //                }
            //            }
            //
            final BufferedWriter out_counts = new BufferedWriter( new FileWriter( outfilename_for_counts ) );
            final BufferedWriter out_dc = new BufferedWriter( new FileWriter( outfilename_for_dc ) );
            final BufferedWriter out_dc_for_go_mapping = new BufferedWriter( new FileWriter( outfilename_for_dc_for_go_mapping ) );
            final BufferedWriter out_dc_for_go_mapping_unique = new BufferedWriter( new FileWriter( outfilename_for_dc_for_go_mapping_unique ) );
            final SortedMap<String, Integer> dc_gain_counts = new TreeMap<String, Integer>();
            for( final PhylogenyNodeIterator it = local_phylogeny_l.iteratorPostorder(); it.hasNext(); ) {
                final PhylogenyNode n = it.next();
                final Set<String> gained_dc = n.getNodeData().getBinaryCharacters().getGainedCharacters();
                for( final String dc : gained_dc ) {
                    if ( dc_gain_counts.containsKey( dc ) ) {
                        dc_gain_counts.put( dc, dc_gain_counts.get( dc ) + 1 );
                    }
                    else {
                        dc_gain_counts.put( dc, 1 );
                    }
                }
            }
            final SortedMap<Integer, Integer> histogram = new TreeMap<Integer, Integer>();
            final SortedMap<Integer, StringBuilder> domain_lists = new TreeMap<Integer, StringBuilder>();
            final SortedMap<Integer, DescriptiveStatistics> dc_reapp_counts_to_protein_length_stats = new TreeMap<Integer, DescriptiveStatistics>();
            final SortedMap<Integer, DescriptiveStatistics> dc_reapp_counts_to_domain_number_stats = new TreeMap<Integer, DescriptiveStatistics>();
            final SortedMap<Integer, DescriptiveStatistics> dc_reapp_counts_to_domain_lengths_stats = new TreeMap<Integer, DescriptiveStatistics>();
            final SortedMap<Integer, PriorityQueue<String>> domain_lists_go = new TreeMap<Integer, PriorityQueue<String>>();
            final SortedMap<Integer, SortedSet<String>> domain_lists_go_unique = new TreeMap<Integer, SortedSet<String>>();
            final Set<String> dcs = dc_gain_counts.keySet();
            final SortedSet<String> more_than_once = new TreeSet<String>();
            DescriptiveStatistics gained_once_lengths_stats = new BasicDescriptiveStatistics();
            DescriptiveStatistics gained_once_domain_count_stats = new BasicDescriptiveStatistics();
            DescriptiveStatistics gained_multiple_times_lengths_stats = new BasicDescriptiveStatistics();
            final DescriptiveStatistics gained_multiple_times_domain_count_stats = new BasicDescriptiveStatistics();
            long gained_multiple_times_domain_length_sum = 0;
            long gained_once_domain_length_sum = 0;
            long gained_multiple_times_domain_length_count = 0;
            long gained_once_domain_length_count = 0;
            for( final String dc : dcs ) {
                final int count = dc_gain_counts.get( dc );
                if ( histogram.containsKey( count ) ) {
                    histogram.put( count, histogram.get( count ) + 1 );
                    domain_lists.get( count ).append( ", " + dc );
                    domain_lists_go.get( count ).addAll( splitDomainCombination( dc ) );
                    domain_lists_go_unique.get( count ).addAll( splitDomainCombination( dc ) );
                }
                else {
                    histogram.put( count, 1 );
                    domain_lists.put( count, new StringBuilder( dc ) );
                    final PriorityQueue<String> q = new PriorityQueue<String>();
                    q.addAll( splitDomainCombination( dc ) );
                    domain_lists_go.put( count, q );
                    final SortedSet<String> set = new TreeSet<String>();
                    set.addAll( splitDomainCombination( dc ) );
                    domain_lists_go_unique.put( count, set );
                }
                if ( protein_length_stats_by_dc != null ) {
                    if ( !dc_reapp_counts_to_protein_length_stats.containsKey( count ) ) {
                        dc_reapp_counts_to_protein_length_stats.put( count, new BasicDescriptiveStatistics() );
                    }
                    dc_reapp_counts_to_protein_length_stats.get( count )
                            .addValue( protein_length_stats_by_dc.get( dc ).arithmeticMean() );
                }
                if ( domain_number_stats_by_dc != null ) {
                    if ( !dc_reapp_counts_to_domain_number_stats.containsKey( count ) ) {
                        dc_reapp_counts_to_domain_number_stats.put( count, new BasicDescriptiveStatistics() );
                    }
                    dc_reapp_counts_to_domain_number_stats.get( count )
                            .addValue( domain_number_stats_by_dc.get( dc ).arithmeticMean() );
                }
                if ( domain_length_stats_by_domain != null ) {
                    if ( !dc_reapp_counts_to_domain_lengths_stats.containsKey( count ) ) {
                        dc_reapp_counts_to_domain_lengths_stats.put( count, new BasicDescriptiveStatistics() );
                    }
                    final String[] ds = dc.split( "=" );
                    dc_reapp_counts_to_domain_lengths_stats.get( count )
                            .addValue( domain_length_stats_by_domain.get( ds[ 0 ] ).arithmeticMean() );
                    dc_reapp_counts_to_domain_lengths_stats.get( count )
                            .addValue( domain_length_stats_by_domain.get( ds[ 1 ] ).arithmeticMean() );
                }
                if ( count > 1 ) {
                    more_than_once.add( dc );
                    if ( protein_length_stats_by_dc != null ) {
                        final DescriptiveStatistics s = protein_length_stats_by_dc.get( dc );
                        for( final double element : s.getData() ) {
                            gained_multiple_times_lengths_stats.addValue( element );
                        }
                    }
                    if ( domain_number_stats_by_dc != null ) {
                        final DescriptiveStatistics s = domain_number_stats_by_dc.get( dc );
                        for( final double element : s.getData() ) {
                            gained_multiple_times_domain_count_stats.addValue( element );
                        }
                    }
                    if ( domain_length_stats_by_domain != null ) {
                        final String[] ds = dc.split( "=" );
                        final DescriptiveStatistics s0 = domain_length_stats_by_domain.get( ds[ 0 ] );
                        final DescriptiveStatistics s1 = domain_length_stats_by_domain.get( ds[ 1 ] );
                        for( final double element : s0.getData() ) {
                            gained_multiple_times_domain_length_sum += element;
                            ++gained_multiple_times_domain_length_count;
                        }
                        for( final double element : s1.getData() ) {
                            gained_multiple_times_domain_length_sum += element;
                            ++gained_multiple_times_domain_length_count;
                        }
                    }
                }
                else {
                    if ( protein_length_stats_by_dc != null ) {
                        final DescriptiveStatistics s = protein_length_stats_by_dc.get( dc );
                        for( final double element : s.getData() ) {
                            gained_once_lengths_stats.addValue( element );
                        }
                    }
                    if ( domain_number_stats_by_dc != null ) {
                        final DescriptiveStatistics s = domain_number_stats_by_dc.get( dc );
                        for( final double element : s.getData() ) {
                            gained_once_domain_count_stats.addValue( element );
                        }
                    }
                    if ( domain_length_stats_by_domain != null ) {
                        final String[] ds = dc.split( "=" );
                        final DescriptiveStatistics s0 = domain_length_stats_by_domain.get( ds[ 0 ] );
                        final DescriptiveStatistics s1 = domain_length_stats_by_domain.get( ds[ 1 ] );
                        for( final double element : s0.getData() ) {
                            gained_once_domain_length_sum += element;
                            ++gained_once_domain_length_count;
                        }
                        for( final double element : s1.getData() ) {
                            gained_once_domain_length_sum += element;
                            ++gained_once_domain_length_count;
                        }
                    }
                }
            }
            final Set<Integer> histogram_keys = histogram.keySet();
            for( final Integer histogram_key : histogram_keys ) {
                final int count = histogram.get( histogram_key );
                final StringBuilder dc = domain_lists.get( histogram_key );
                out_counts.write( histogram_key + "\t" + count + ForesterUtil.LINE_SEPARATOR );
                out_dc.write( histogram_key + "\t" + dc + ForesterUtil.LINE_SEPARATOR );
                out_dc_for_go_mapping.write( "#" + histogram_key + ForesterUtil.LINE_SEPARATOR );
                final Object[] sorted = domain_lists_go.get( histogram_key ).toArray();
                Arrays.sort( sorted );
                for( final Object domain : sorted ) {
                    out_dc_for_go_mapping.write( domain + ForesterUtil.LINE_SEPARATOR );
                }
                out_dc_for_go_mapping_unique.write( "#" + histogram_key + ForesterUtil.LINE_SEPARATOR );
                for( final String domain : domain_lists_go_unique.get( histogram_key ) ) {
                    out_dc_for_go_mapping_unique.write( domain + ForesterUtil.LINE_SEPARATOR );
                }
            }
            out_counts.close();
            out_dc.close();
            out_dc_for_go_mapping.close();
            out_dc_for_go_mapping_unique.close();
            final SortedMap<String, Integer> lca_rank_counts = new TreeMap<String, Integer>();
            final SortedMap<String, Integer> lca_ancestor_species_counts = new TreeMap<String, Integer>();
            for( final String dc : more_than_once ) {
                final List<PhylogenyNode> nodes = new ArrayList<PhylogenyNode>();
                for( final PhylogenyNodeIterator it = local_phylogeny_l.iteratorExternalForward(); it.hasNext(); ) {
                    final PhylogenyNode n = it.next();
                    if ( n.getNodeData().getBinaryCharacters().getGainedCharacters().contains( dc ) ) {
                        nodes.add( n );
                    }
                }
                for( int i = 0; i < ( nodes.size() - 1 ); ++i ) {
                    for( int j = i + 1; j < nodes.size(); ++j ) {
                        final PhylogenyNode lca = PhylogenyMethods.calculateLCA( nodes.get( i ), nodes.get( j ) );
                        String rank = "unknown";
                        if ( lca.getNodeData().isHasTaxonomy()
                                && !ForesterUtil.isEmpty( lca.getNodeData().getTaxonomy().getRank() ) ) {
                            rank = lca.getNodeData().getTaxonomy().getRank();
                        }
                        addToCountMap( lca_rank_counts, rank );
                        String lca_species;
                        if ( lca.getNodeData().isHasTaxonomy()
                                && !ForesterUtil.isEmpty( lca.getNodeData().getTaxonomy().getScientificName() ) ) {
                            lca_species = lca.getNodeData().getTaxonomy().getScientificName();
                        }
                        else if ( lca.getNodeData().isHasTaxonomy()
                                && !ForesterUtil.isEmpty( lca.getNodeData().getTaxonomy().getCommonName() ) ) {
                            lca_species = lca.getNodeData().getTaxonomy().getCommonName();
                        }
                        else {
                            lca_species = lca.getName();
                        }
                        addToCountMap( lca_ancestor_species_counts, lca_species );
                    }
                }
            }
            final BufferedWriter out_for_rank_counts = new BufferedWriter( new FileWriter( outfilename_for_rank_counts ) );
            final BufferedWriter out_for_ancestor_species_counts = new BufferedWriter( new FileWriter( outfilename_for_ancestor_species_counts ) );
            ForesterUtil.map2writer( out_for_rank_counts, lca_rank_counts, "\t", ForesterUtil.LINE_SEPARATOR );
            ForesterUtil.map2writer( out_for_ancestor_species_counts,
                                     lca_ancestor_species_counts,
                                     "\t",
                                     ForesterUtil.LINE_SEPARATOR );
            out_for_rank_counts.close();
            out_for_ancestor_species_counts.close();
            if ( !ForesterUtil.isEmpty( outfilename_for_protein_stats ) && ( ( domain_length_stats_by_domain != null )
                    || ( protein_length_stats_by_dc != null ) || ( domain_number_stats_by_dc != null ) ) ) {
                final BufferedWriter w = new BufferedWriter( new FileWriter( outfilename_for_protein_stats ) );
                w.write( "Domain Lengths: " );
                w.write( "\n" );
                if ( domain_length_stats_by_domain != null ) {
                    for( final Entry<Integer, DescriptiveStatistics> entry : dc_reapp_counts_to_domain_lengths_stats
                            .entrySet() ) {
                        w.write( entry.getKey().toString() );
                        w.write( "\t" + entry.getValue().arithmeticMean() );
                        w.write( "\t" + entry.getValue().median() );
                        w.write( "\n" );
                    }
                }
                w.flush();
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Protein Lengths: " );
                w.write( "\n" );
                if ( protein_length_stats_by_dc != null ) {
                    for( final Entry<Integer, DescriptiveStatistics> entry : dc_reapp_counts_to_protein_length_stats
                            .entrySet() ) {
                        w.write( entry.getKey().toString() );
                        w.write( "\t" + entry.getValue().arithmeticMean() );
                        w.write( "\t" + entry.getValue().median() );
                        w.write( "\n" );
                    }
                }
                w.flush();
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Number of domains: " );
                w.write( "\n" );
                if ( domain_number_stats_by_dc != null ) {
                    for( final Entry<Integer, DescriptiveStatistics> entry : dc_reapp_counts_to_domain_number_stats
                            .entrySet() ) {
                        w.write( entry.getKey().toString() );
                        w.write( "\t" + entry.getValue().arithmeticMean() );
                        w.write( "\t" + entry.getValue().median() );
                        w.write( "\n" );
                    }
                }
                w.flush();
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained once, domain lengths:" );
                w.write( "\n" );
                w.write( "N: " + gained_once_domain_length_count );
                w.write( "\n" );
                w.write( "Avg: " + ( ( double ) gained_once_domain_length_sum / gained_once_domain_length_count ) );
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained multiple times, domain lengths:" );
                w.write( "\n" );
                w.write( "N: " + gained_multiple_times_domain_length_count );
                w.write( "\n" );
                w.write( "Avg: " + ( ( double ) gained_multiple_times_domain_length_sum
                        / gained_multiple_times_domain_length_count ) );
                w.write( "\n" );
                w.write( "\n" );
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained once, protein lengths:" );
                w.write( "\n" );
                w.write( gained_once_lengths_stats.toString() );
                gained_once_lengths_stats = null;
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained once, domain counts:" );
                w.write( "\n" );
                w.write( gained_once_domain_count_stats.toString() );
                gained_once_domain_count_stats = null;
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained multiple times, protein lengths:" );
                w.write( "\n" );
                w.write( gained_multiple_times_lengths_stats.toString() );
                gained_multiple_times_lengths_stats = null;
                w.write( "\n" );
                w.write( "\n" );
                w.write( "Gained multiple times, domain counts:" );
                w.write( "\n" );
                w.write( gained_multiple_times_domain_count_stats.toString() );
                w.flush();
                w.close();
            }
        }
        catch ( final IOException e ) {
            ForesterUtil.printWarningMessage( surfacing.PRG_NAME, "Failure to write: " + e );
        }
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote independent domain combination gains fitch counts to ["
                                             + outfilename_for_counts + "]" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote independent domain combination gains fitch lists to [" + outfilename_for_dc
                                             + "]" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote independent domain combination gains fitch lists to (for GO mapping) ["
                                             + outfilename_for_dc_for_go_mapping + "]" );
        ForesterUtil.programMessage( surfacing.PRG_NAME,
                                     "Wrote independent domain combination gains fitch lists to (for GO mapping, unique) ["
                                             + outfilename_for_dc_for_go_mapping_unique + "]" );
    }

    private static SortedSet<String> collectAllDomainsChangedOnSubtree( final PhylogenyNode subtree_root,
                                                                        final boolean get_gains ) {
        final SortedSet<String> domains = new TreeSet<String>();
        for( final PhylogenyNode descendant : PhylogenyMethods.getAllDescendants( subtree_root ) ) {
            final BinaryCharacters chars = descendant.getNodeData().getBinaryCharacters();
            if ( get_gains ) {
                domains.addAll( chars.getGainedCharacters() );
            }
            else {
                domains.addAll( chars.getLostCharacters() );
            }
        }
        return domains;
    }

    private static File createBaseDirForPerNodeDomainFiles( final String base_dir,
                                                            final boolean domain_combinations,
                                                            final CharacterStateMatrix.GainLossStates state,
                                                            final String outfile ) {
        File per_node_go_mapped_domain_gain_loss_files_base_dir = new File( new File( outfile ).getParent()
                + ForesterUtil.FILE_SEPARATOR + base_dir );
        if ( !per_node_go_mapped_domain_gain_loss_files_base_dir.exists() ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir.mkdir();
        }
        if ( domain_combinations ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                    + ForesterUtil.FILE_SEPARATOR + "DC" );
        }
        else {
            per_node_go_mapped_domain_gain_loss_files_base_dir = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                    + ForesterUtil.FILE_SEPARATOR + "DOMAINS" );
        }
        if ( !per_node_go_mapped_domain_gain_loss_files_base_dir.exists() ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir.mkdir();
        }
        if ( state == GainLossStates.GAIN ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                    + ForesterUtil.FILE_SEPARATOR + "GAINS" );
        }
        else if ( state == GainLossStates.LOSS ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                    + ForesterUtil.FILE_SEPARATOR + "LOSSES" );
        }
        else {
            per_node_go_mapped_domain_gain_loss_files_base_dir = new File( per_node_go_mapped_domain_gain_loss_files_base_dir
                    + ForesterUtil.FILE_SEPARATOR + "PRESENT" );
        }
        if ( !per_node_go_mapped_domain_gain_loss_files_base_dir.exists() ) {
            per_node_go_mapped_domain_gain_loss_files_base_dir.mkdir();
        }
        return per_node_go_mapped_domain_gain_loss_files_base_dir;
    }

    private static SortedSet<BinaryDomainCombination> createSetOfAllBinaryDomainCombinationsPerGenome( final GenomeWideCombinableDomains gwcd ) {
        final SortedMap<String, CombinableDomains> cds = gwcd.getAllCombinableDomainsIds();
        final SortedSet<BinaryDomainCombination> binary_combinations = new TreeSet<BinaryDomainCombination>();
        for( final String domain_id : cds.keySet() ) {
            final CombinableDomains cd = cds.get( domain_id );
            binary_combinations.addAll( cd.toBinaryDomainCombinations() );
        }
        return binary_combinations;
    }

    private static void printSomeStats( final DescriptiveStatistics stats, final AsciiHistogram histo, final Writer w )
            throws IOException {
        w.write( "<hr>" );
        w.write( "<br>" );
        w.write( SurfacingConstants.NL );
        w.write( "<tt><pre>" );
        w.write( SurfacingConstants.NL );
        if ( histo != null ) {
            w.write( histo.toStringBuffer( 20, '|', 40, 5 ).toString() );
            w.write( SurfacingConstants.NL );
        }
        w.write( "</pre></tt>" );
        w.write( SurfacingConstants.NL );
        w.write( "<table>" );
        w.write( SurfacingConstants.NL );
        w.write( "<tr><td>N: </td><td>" + stats.getN() + "</td></tr>" );
        w.write( SurfacingConstants.NL );
        w.write( "<tr><td>Min: </td><td>" + stats.getMin() + "</td></tr>" );
        w.write( SurfacingConstants.NL );
        w.write( "<tr><td>Max: </td><td>" + stats.getMax() + "</td></tr>" );
        w.write( SurfacingConstants.NL );
        w.write( "<tr><td>Mean: </td><td>" + stats.arithmeticMean() + "</td></tr>" );
        w.write( SurfacingConstants.NL );
        if ( stats.getN() > 1 ) {
            w.write( "<tr><td>SD: </td><td>" + stats.sampleStandardDeviation() + "</td></tr>" );
        }
        else {
            w.write( "<tr><td>SD: </td><td>n/a</td></tr>" );
        }
        w.write( SurfacingConstants.NL );
        w.write( "</table>" );
        w.write( SurfacingConstants.NL );
        w.write( "<br>" );
        w.write( SurfacingConstants.NL );
    }

    private static List<String> splitDomainCombination( final String dc ) {
        final String[] s = dc.split( "=" );
        if ( s.length != 2 ) {
            ForesterUtil.printErrorMessage( surfacing.PRG_NAME,
                                            "Stringyfied domain combination has illegal format: " + dc );
            System.exit( -1 );
        }
        final List<String> l = new ArrayList<String>( 2 );
        l.add( s[ 0 ] );
        l.add( s[ 1 ] );
        return l;
    }

    private static void writeAllEncounteredPfamsToFile( final Map<String, List<GoId>> domain_id_to_go_ids_map,
                                                        final Map<GoId, GoTerm> go_id_to_term_map,
                                                        final String outfile_name,
                                                        final SortedSet<String> all_pfams_encountered ) {
        final File all_pfams_encountered_file = new File( outfile_name + surfacing.ALL_PFAMS_ENCOUNTERED_SUFFIX );
        final File all_pfams_encountered_with_go_annotation_file = new File( outfile_name
                + surfacing.ALL_PFAMS_ENCOUNTERED_WITH_GO_ANNOTATION_SUFFIX );
        final File encountered_pfams_summary_file = new File( outfile_name
                + surfacing.ENCOUNTERED_PFAMS_SUMMARY_SUFFIX );
        int biological_process_counter = 0;
        int cellular_component_counter = 0;
        int molecular_function_counter = 0;
        int pfams_with_mappings_counter = 0;
        int pfams_without_mappings_counter = 0;
        int pfams_without_mappings_to_bp_or_mf_counter = 0;
        int pfams_with_mappings_to_bp_or_mf_counter = 0;
        try {
            final Writer all_pfams_encountered_writer = new BufferedWriter( new FileWriter( all_pfams_encountered_file ) );
            final Writer all_pfams_encountered_with_go_annotation_writer = new BufferedWriter( new FileWriter( all_pfams_encountered_with_go_annotation_file ) );
            final Writer summary_writer = new BufferedWriter( new FileWriter( encountered_pfams_summary_file ) );
            summary_writer.write( "# Pfam to GO mapping summary" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Actual summary is at the end of this file." );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Encountered Pfams without a GO mapping:" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            for( final String pfam : all_pfams_encountered ) {
                all_pfams_encountered_writer.write( pfam );
                all_pfams_encountered_writer.write( ForesterUtil.LINE_SEPARATOR );
                final String domain_id = new String( pfam );
                if ( domain_id_to_go_ids_map.containsKey( domain_id ) ) {
                    ++pfams_with_mappings_counter;
                    all_pfams_encountered_with_go_annotation_writer.write( pfam );
                    all_pfams_encountered_with_go_annotation_writer.write( ForesterUtil.LINE_SEPARATOR );
                    final List<GoId> go_ids = domain_id_to_go_ids_map.get( domain_id );
                    boolean maps_to_bp = false;
                    boolean maps_to_cc = false;
                    boolean maps_to_mf = false;
                    for( final GoId go_id : go_ids ) {
                        final GoTerm go_term = go_id_to_term_map.get( go_id );
                        if ( go_term.getGoNameSpace().isBiologicalProcess() ) {
                            maps_to_bp = true;
                        }
                        else if ( go_term.getGoNameSpace().isCellularComponent() ) {
                            maps_to_cc = true;
                        }
                        else if ( go_term.getGoNameSpace().isMolecularFunction() ) {
                            maps_to_mf = true;
                        }
                    }
                    if ( maps_to_bp ) {
                        ++biological_process_counter;
                    }
                    if ( maps_to_cc ) {
                        ++cellular_component_counter;
                    }
                    if ( maps_to_mf ) {
                        ++molecular_function_counter;
                    }
                    if ( maps_to_bp || maps_to_mf ) {
                        ++pfams_with_mappings_to_bp_or_mf_counter;
                    }
                    else {
                        ++pfams_without_mappings_to_bp_or_mf_counter;
                    }
                }
                else {
                    ++pfams_without_mappings_to_bp_or_mf_counter;
                    ++pfams_without_mappings_counter;
                    summary_writer.write( pfam );
                    summary_writer.write( ForesterUtil.LINE_SEPARATOR );
                }
            }
            all_pfams_encountered_writer.close();
            all_pfams_encountered_with_go_annotation_writer.close();
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote all [" + all_pfams_encountered.size() + "] encountered Pfams to: \""
                                                 + all_pfams_encountered_file + "\"" );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote all [" + pfams_with_mappings_counter
                                                 + "] encountered Pfams with GO mappings to: \""
                                                 + all_pfams_encountered_with_go_annotation_file + "\"" );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote summary (including all [" + pfams_without_mappings_counter
                                                 + "] encountered Pfams without GO mappings) to: \""
                                                 + encountered_pfams_summary_file + "\"" );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Sum of Pfams encountered                : " + all_pfams_encountered.size() );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Pfams without a mapping                 : " + pfams_without_mappings_counter
                                                 + " [" + ( ( 100 * pfams_without_mappings_counter )
                                                         / all_pfams_encountered.size() )
                                                 + "%]" );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Pfams without mapping to proc. or func. : "
                                                 + pfams_without_mappings_to_bp_or_mf_counter + " ["
                                                 + ( ( 100 * pfams_without_mappings_to_bp_or_mf_counter )
                                                         / all_pfams_encountered.size() )
                                                 + "%]" );
            ForesterUtil
                    .programMessage( surfacing.PRG_NAME,
                                     "Pfams with a mapping                    : " + pfams_with_mappings_counter + " ["
                                             + ( ( 100 * pfams_with_mappings_counter ) / all_pfams_encountered.size() )
                                             + "%]" );
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Pfams with a mapping to proc. or func.  : "
                                                 + pfams_with_mappings_to_bp_or_mf_counter + " ["
                                                 + ( ( 100 * pfams_with_mappings_to_bp_or_mf_counter )
                                                         / all_pfams_encountered.size() )
                                                 + "%]" );
            ForesterUtil
                    .programMessage( surfacing.PRG_NAME,
                                     "Pfams with mapping to biological process: " + biological_process_counter + " ["
                                             + ( ( 100 * biological_process_counter ) / all_pfams_encountered.size() )
                                             + "%]" );
            ForesterUtil
                    .programMessage( surfacing.PRG_NAME,
                                     "Pfams with mapping to molecular function: " + molecular_function_counter + " ["
                                             + ( ( 100 * molecular_function_counter ) / all_pfams_encountered.size() )
                                             + "%]" );
            ForesterUtil
                    .programMessage( surfacing.PRG_NAME,
                                     "Pfams with mapping to cellular component: " + cellular_component_counter + " ["
                                             + ( ( 100 * cellular_component_counter ) / all_pfams_encountered.size() )
                                             + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Sum of Pfams encountered                : " + all_pfams_encountered.size() );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams without a mapping                 : " + pfams_without_mappings_counter + " ["
                    + ( ( 100 * pfams_without_mappings_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams without mapping to proc. or func. : "
                    + pfams_without_mappings_to_bp_or_mf_counter + " ["
                    + ( ( 100 * pfams_without_mappings_to_bp_or_mf_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams with a mapping                    : " + pfams_with_mappings_counter + " ["
                    + ( ( 100 * pfams_with_mappings_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams with a mapping to proc. or func.  : "
                    + pfams_with_mappings_to_bp_or_mf_counter + " ["
                    + ( ( 100 * pfams_with_mappings_to_bp_or_mf_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams with mapping to biological process: " + biological_process_counter + " ["
                    + ( ( 100 * biological_process_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams with mapping to molecular function: " + molecular_function_counter + " ["
                    + ( ( 100 * molecular_function_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.write( "# Pfams with mapping to cellular component: " + cellular_component_counter + " ["
                    + ( ( 100 * cellular_component_counter ) / all_pfams_encountered.size() ) + "%]" );
            summary_writer.write( ForesterUtil.LINE_SEPARATOR );
            summary_writer.close();
        }
        catch ( final IOException e ) {
            ForesterUtil.printWarningMessage( surfacing.PRG_NAME, "Failure to write: " + e );
        }
    }

    private final static void writeColorLabels( final String l, final Color c, final Writer w ) throws IOException {
        w.write( "<tr><td><b><span style=\"color:" );
        w.write( String.format( "#%02x%02x%02x", c.getRed(), c.getGreen(), c.getBlue() ) );
        w.write( "\">" );
        w.write( l );
        w.write( "</span></b></td></tr>" );
        w.write( SurfacingConstants.NL );
    }

    private static void writeDomainData( final Map<String, List<GoId>> domain_id_to_go_ids_map,
                                         final Map<GoId, GoTerm> go_id_to_term_map,
                                         final GoNameSpace go_namespace_limit,
                                         final Writer out,
                                         final String domain_0,
                                         final String domain_1,
                                         final String prefix_for_html,
                                         final String character_separator_for_non_html_output,
                                         final Map<String, Set<String>>[] domain_id_to_secondary_features_maps,
                                         final Set<GoId> all_go_ids )
            throws IOException {
        boolean any_go_annotation_present = false;
        boolean first_has_no_go = false;
        int domain_count = 2; // To distinguish between domains and binary domain combinations.
        if ( ForesterUtil.isEmpty( domain_1 ) ) {
            domain_count = 1;
        }
        // The following has a difficult to understand logic.
        for( int d = 0; d < domain_count; ++d ) {
            List<GoId> go_ids = null;
            boolean go_annotation_present = false;
            if ( d == 0 ) {
                if ( domain_id_to_go_ids_map.containsKey( domain_0 ) ) {
                    go_annotation_present = true;
                    any_go_annotation_present = true;
                    go_ids = domain_id_to_go_ids_map.get( domain_0 );
                }
                else {
                    first_has_no_go = true;
                }
            }
            else {
                if ( domain_id_to_go_ids_map.containsKey( domain_1 ) ) {
                    go_annotation_present = true;
                    any_go_annotation_present = true;
                    go_ids = domain_id_to_go_ids_map.get( domain_1 );
                }
            }
            if ( go_annotation_present ) {
                boolean first = ( ( d == 0 ) || ( ( d == 1 ) && first_has_no_go ) );
                for( final GoId go_id : go_ids ) {
                    out.write( "<tr>" );
                    if ( first ) {
                        first = false;
                        writeDomainIdsToHtml( out,
                                              domain_0,
                                              domain_1,
                                              prefix_for_html,
                                              domain_id_to_secondary_features_maps );
                    }
                    else {
                        out.write( "<td></td>" );
                    }
                    if ( !go_id_to_term_map.containsKey( go_id ) ) {
                        throw new IllegalArgumentException( "GO-id [" + go_id + "] not found in GO-id to GO-term map" );
                    }
                    final GoTerm go_term = go_id_to_term_map.get( go_id );
                    if ( ( go_namespace_limit == null ) || go_namespace_limit.equals( go_term.getGoNameSpace() ) ) {
                        // final String top = GoUtils.getPenultimateGoTerm( go_term, go_id_to_term_map ).getName();
                        final String go_id_str = go_id.getId();
                        out.write( "<td>" );
                        out.write( "<a href=\"" + SurfacingConstants.AMIGO_LINK + go_id_str
                                + "\" target=\"amigo_window\">" + go_id_str + "</a>" );
                        out.write( "</td><td>" );
                        out.write( go_term.getName() );
                        if ( domain_count == 2 ) {
                            out.write( " (" + d + ")" );
                        }
                        out.write( "</td><td>" );
                        // out.write( top );
                        // out.write( "</td><td>" );
                        out.write( "[" );
                        out.write( go_term.getGoNameSpace().toShortString() );
                        out.write( "]" );
                        out.write( "</td>" );
                        if ( all_go_ids != null ) {
                            all_go_ids.add( go_id );
                        }
                    }
                    else {
                        out.write( "<td>" );
                        out.write( "</td><td>" );
                        out.write( "</td><td>" );
                        out.write( "</td><td>" );
                        out.write( "</td>" );
                    }
                    out.write( "</tr>" );
                    out.write( SurfacingConstants.NL );
                }
            }
        } //  for( int d = 0; d < domain_count; ++d )
        if ( !any_go_annotation_present ) {
            out.write( "<tr>" );
            writeDomainIdsToHtml( out, domain_0, domain_1, prefix_for_html, domain_id_to_secondary_features_maps );
            out.write( "<td>" );
            out.write( "</td><td>" );
            out.write( "</td><td>" );
            out.write( "</td><td>" );
            out.write( "</td>" );
            out.write( "</tr>" );
            out.write( SurfacingConstants.NL );
        }
    }

    private static void writeDomainIdsToHtml( final Writer out,
                                              final String domain_0,
                                              final String domain_1,
                                              final String prefix_for_detailed_html,
                                              final Map<String, Set<String>>[] domain_id_to_secondary_features_maps )
            throws IOException {
        out.write( "<td>" );
        if ( !ForesterUtil.isEmpty( prefix_for_detailed_html ) ) {
            out.write( prefix_for_detailed_html );
            out.write( " " );
        }
        out.write( "<a href=\"" + SurfacingConstants.PFAM_FAMILY_ID_LINK + domain_0 + "\">" + domain_0 + "</a>" );
        out.write( "</td>" );
    }

    private static void writeDomainsToIndividualFilePerTreeNode( final Writer individual_files_writer,
                                                                 final String domain_0,
                                                                 final String domain_1 )
            throws IOException {
        individual_files_writer.write( domain_0 );
        individual_files_writer.write( ForesterUtil.LINE_SEPARATOR );
        if ( !ForesterUtil.isEmpty( domain_1 ) ) {
            individual_files_writer.write( domain_1 );
            individual_files_writer.write( ForesterUtil.LINE_SEPARATOR );
        }
    }

    private static void writePfamsToFile( final String outfile_name, final SortedSet<String> pfams ) {
        try {
            final Writer writer = new BufferedWriter( new FileWriter( new File( outfile_name ) ) );
            for( final String pfam : pfams ) {
                writer.write( pfam );
                writer.write( ForesterUtil.LINE_SEPARATOR );
            }
            writer.close();
            ForesterUtil.programMessage( surfacing.PRG_NAME,
                                         "Wrote " + pfams.size() + " pfams to [" + outfile_name + "]" );
        }
        catch ( final IOException e ) {
            ForesterUtil.printWarningMessage( surfacing.PRG_NAME, "Failure to write: " + e );
        }
    }

    private static void writeToNexus( final String outfile_name,
                                      final CharacterStateMatrix<BinaryStates> matrix,
                                      final Phylogeny phylogeny ) {
        if ( !( matrix instanceof BasicCharacterStateMatrix ) ) {
            throw new IllegalArgumentException( "can only write matrices of type [" + BasicCharacterStateMatrix.class
                    + "] to nexus" );
        }
        final BasicCharacterStateMatrix<BinaryStates> my_matrix = ( org.forester.evoinference.matrix.character.BasicCharacterStateMatrix<BinaryStates> ) matrix;
        final List<Phylogeny> phylogenies = new ArrayList<Phylogeny>( 1 );
        phylogenies.add( phylogeny );
        try {
            final BufferedWriter w = new BufferedWriter( new FileWriter( outfile_name ) );
            w.write( NexusConstants.NEXUS );
            w.write( ForesterUtil.LINE_SEPARATOR );
            my_matrix.writeNexusTaxaBlock( w );
            my_matrix.writeNexusBinaryChractersBlock( w );
            PhylogenyWriter.writeNexusTreesBlock( w, phylogenies, NH_CONVERSION_SUPPORT_VALUE_STYLE.NONE );
            w.flush();
            w.close();
            ForesterUtil.programMessage( surfacing.PRG_NAME, "Wrote Nexus file: \"" + outfile_name + "\"" );
        }
        catch ( final IOException e ) {
            ForesterUtil.fatalError( surfacing.PRG_NAME, e.getMessage() );
        }
    }

    private static void writeToNexus( final String outfile_name,
                                      final DomainParsimonyCalculator domain_parsimony,
                                      final Phylogeny phylogeny ) {
        writeToNexus( outfile_name + surfacing.NEXUS_EXTERNAL_DOMAINS,
                      domain_parsimony.createMatrixOfDomainPresenceOrAbsence(),
                      phylogeny );
        writeToNexus( outfile_name + surfacing.NEXUS_EXTERNAL_DOMAIN_COMBINATIONS,
                      domain_parsimony.createMatrixOfBinaryDomainCombinationPresenceOrAbsence(),
                      phylogeny );
    }

    final static class DomainComparator implements Comparator<Domain> {

        final private boolean _ascending;

        public DomainComparator( final boolean ascending ) {
            _ascending = ascending;
        }

        @Override
        public final int compare( final Domain d0, final Domain d1 ) {
            if ( d0.getFrom() < d1.getFrom() ) {
                return _ascending ? -1 : 1;
            }
            else if ( d0.getFrom() > d1.getFrom() ) {
                return _ascending ? 1 : -1;
            }
            return 0;
        }
    }
}