VCFview.java

/* VCFview
 *
 * created: July 2010
 *
 * This file is part of Artemis
 *
 * Copyright(C) 2010  Genome Research Limited
 *
 * This program is free software; you can redistribute it and/or
 * modify it under the terms of the GNU General Public License
 * as published by the Free Software Foundation; either version 2
 * of the License, or(at your option) any later version.
 *
 * This program 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 General Public License for more details.
 *
 * You should have received a copy of the GNU General Public License
 * along with this program; if not, write to the Free Software
 * Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA  02111-1307, USA.
 *
 */

package uk.ac.sanger.artemis.components.variant;
import java.awt.AlphaComposite;
import java.awt.BorderLayout;
import java.awt.Color;
import java.awt.Component;
import java.awt.Composite;
import java.awt.Container;
import java.awt.Cursor;
import java.awt.Dimension;
import java.awt.FlowLayout;
import java.awt.FontMetrics;
import java.awt.Frame;
import java.awt.Graphics;
import java.awt.Graphics2D;
import java.awt.Insets;
import java.awt.Point;
import java.awt.Rectangle;
import java.awt.event.ActionEvent;
import java.awt.event.ActionListener;
import java.awt.event.AdjustmentEvent;
import java.awt.event.AdjustmentListener;
import java.awt.event.ItemEvent;
import java.awt.event.ItemListener;
import java.awt.event.MouseAdapter;
import java.awt.event.MouseEvent;
import java.awt.event.MouseMotionListener;
import java.io.File;
import java.io.FileInputStream;
import java.io.FileOutputStream;
import java.io.IOException;
import java.io.InputStream;
import java.net.URL;
import java.util.Hashtable;
import java.util.List;
import java.util.Vector;
import java.util.regex.Pattern;

import javax.swing.BorderFactory;
import javax.swing.ButtonGroup;
import javax.swing.JButton;
import javax.swing.JCheckBox;
import javax.swing.JCheckBoxMenuItem;
import javax.swing.JComboBox;
import javax.swing.JComponent;
import javax.swing.JFrame;
import javax.swing.JMenu;
import javax.swing.JMenuBar;
import javax.swing.JMenuItem;
import javax.swing.JOptionPane;
import javax.swing.JPanel;
import javax.swing.JPopupMenu;
import javax.swing.JRadioButtonMenuItem;
import javax.swing.JScrollBar;
import javax.swing.JScrollPane;
import javax.swing.JSeparator;
import javax.swing.border.Border;
import javax.swing.border.EmptyBorder;
import javax.swing.text.JTextComponent;

import net.sf.samtools.util.BlockCompressedInputStream;

import org.apache.log4j.Level;

import uk.ac.sanger.artemis.Entry;
import uk.ac.sanger.artemis.EntryGroup;
import uk.ac.sanger.artemis.Feature;
import uk.ac.sanger.artemis.FeatureKeyPredicate;
import uk.ac.sanger.artemis.FeatureVector;
import uk.ac.sanger.artemis.Options;
import uk.ac.sanger.artemis.Selection;
import uk.ac.sanger.artemis.SelectionChangeEvent;
import uk.ac.sanger.artemis.SelectionChangeListener;
import uk.ac.sanger.artemis.SimpleEntryGroup;
import uk.ac.sanger.artemis.components.DisplayAdjustmentEvent;
import uk.ac.sanger.artemis.components.DisplayAdjustmentListener;
import uk.ac.sanger.artemis.components.EntryEdit;
import uk.ac.sanger.artemis.components.EntryFileDialog;
import uk.ac.sanger.artemis.components.FeatureDisplay;
import uk.ac.sanger.artemis.components.FileViewer;
import uk.ac.sanger.artemis.components.MessageDialog;
import uk.ac.sanger.artemis.components.MultiComparator;
import uk.ac.sanger.artemis.components.alignment.FileSelectionDialog;
import uk.ac.sanger.artemis.components.genebuilder.AutoCompleteComboDocument;
import uk.ac.sanger.artemis.editor.MultiLineToolTipUI;
import uk.ac.sanger.artemis.io.EntryInformation;
import uk.ac.sanger.artemis.io.Key;
import uk.ac.sanger.artemis.io.Range;
import uk.ac.sanger.artemis.io.RangeVector;
import uk.ac.sanger.artemis.sequence.Bases;
import uk.ac.sanger.artemis.sequence.MarkerRange;
import uk.ac.sanger.artemis.sequence.NoSequenceException;
import uk.ac.sanger.artemis.util.Document;
import uk.ac.sanger.artemis.util.DocumentFactory;
import uk.ac.sanger.artemis.util.FTPSeekableStream;
import uk.ac.sanger.artemis.util.OutOfRangeException;


public class VCFview extends JPanel
             implements DisplayAdjustmentListener, SelectionChangeListener
{
  private static final long serialVersionUID = 1L;
  private JScrollBar scrollBar;
  private JPanel vcfPanel;
  private AbstractVCFReader vcfReaders[];
  private List<String> vcfFiles;
  private List<Integer> hideVcfList = new Vector<Integer>();
  
  private String header[];
  private FeatureDisplay feature_display;
  private Selection selection;
  private int nbasesInView;
  protected int seqLength;
  private EntryGroup entryGroup;
  private String chr;
  private VCFRecord mouseVCF;
  private int mouseOverIndex = -1;
  
  private GraphPanel graphPanel;

//record of where a mouse drag starts
  private int dragStart = -1;
  private JPopupMenu popup;
  private JMenu vcfFilesMenu = new JMenu("VCF files");
  private int LINE_HEIGHT = 15;
  
  protected boolean showSynonymous = true;
  protected boolean showNonSynonymous = true;
  protected boolean showDeletions = true;
  protected boolean showInsertions = true;
  protected boolean showMultiAlleles = true;
  // show variants that do not overlap CDS
  protected boolean showNonOverlappings = true;
  protected boolean showNonVariants = false;
  
  private boolean markAsNewStop = false;
  
  private boolean showLabels = false;
  
  private JCheckBoxMenuItem markNewStops =
    new JCheckBoxMenuItem("Mark new stops within CDS features", true);
  
  private static int VARIANT_COLOUR_SCHEME = 0;
  private static int SYN_COLOUR_SCHEME     = 1;
  private static int QUAL_COLOUR_SCHEME    = 2;
  
  private int colourScheme = 0;
  private Color colMap[] = makeColours(Color.RED, 255);
  private Color lighterGrey = new Color(220,220,220);

  Hashtable<String, Integer> offsetLengths = null;
  private boolean concatSequences = false;
  protected static Pattern tabPattern = Pattern.compile("\t");
  
  public static String VCFFILE_SUFFIX = ".*\\.[bv]{1}cf(\\.gz)*$";
  private static String FILE_SUFFIX = "\\.[bv]{1}cf(\\.gz)*$";

  private List<Integer> cacheVariantLines;

  public static org.apache.log4j.Logger logger4j = 
    org.apache.log4j.Logger.getLogger(VCFview.class);

  public VCFview(final JFrame frame,
                 final JPanel vcfPanel,
                 final List<String> vcfFiles, 
                 final int nbasesInView,
                 final int seqLength,
                 final String chr,
                 final String reference,
                 final FeatureDisplay feature_display)
  {
    super();
    
    this.nbasesInView = nbasesInView;
    this.seqLength = seqLength;
    this.chr = chr;
    this.feature_display = feature_display;
    this.vcfPanel = vcfPanel;
    this.vcfFiles = vcfFiles;
 
    setBackground(Color.white);
    MultiLineToolTipUI.initialize();
    setToolTipText("");
    vcfPanel.setPreferredSize(new Dimension(900, 
        (vcfFiles.size()+1)*(LINE_HEIGHT+5)));
    
    if(feature_display != null)
      this.entryGroup = feature_display.getEntryGroup();
    else if(reference != null)
      this.entryGroup = getReference(reference);
    if(entryGroup != null)
      this.seqLength = entryGroup.getSequenceEntry().getBases().getLength();
    
    try
    {
      vcfReaders = new AbstractVCFReader[vcfFiles.size()];
      header = new String[vcfFiles.size()];
      
      for(int i=0; i<vcfFiles.size(); i++)
      {
        header[i] = readHeader(vcfFiles.get(i), i);
      }
    }
    catch(java.lang.UnsupportedClassVersionError err)
    {
      JOptionPane.showMessageDialog(null, 
          "This requires Java 1.6 or higher.", 
          "Check Java Version", JOptionPane.WARNING_MESSAGE);
    }

    final JScrollPane jspView = new JScrollPane(this, 
        JScrollPane.VERTICAL_SCROLLBAR_AS_NEEDED,
        JScrollPane.HORIZONTAL_SCROLLBAR_NEVER);
    
    vcfPanel.setLayout(new BorderLayout());
    vcfPanel.add(jspView, BorderLayout.CENTER);
    
    JPanel bottomPanel = new JPanel(new BorderLayout());
    graphPanel = new GraphPanel(this);
    graphPanel.setBorder(BorderFactory.createMatteBorder(1, 0, 1, 0, Color.gray));
    graphPanel.setPreferredSize(new Dimension(900, 100));
    graphPanel.setVisible(false);
    
    bottomPanel.add(graphPanel, BorderLayout.CENTER);
    vcfPanel.add(bottomPanel, BorderLayout.SOUTH);
    
    if(this.nbasesInView > this.seqLength)
      this.nbasesInView = this.seqLength/2;

    scrollBar = new JScrollBar(JScrollBar.HORIZONTAL, 1, this.nbasesInView, 1, this.seqLength);
    scrollBar.setUnitIncrement(nbasesInView/20);
    scrollBar.addAdjustmentListener(new AdjustmentListener()
    {
      public void adjustmentValueChanged(AdjustmentEvent e)
      {
        repaint();
      }
    });
    
    //
    //
    addMouseListener(new PopupListener());
    
    //
    createMenus(frame, jspView);
    setDisplay();
    
    if(feature_display == null)
    {
      bottomPanel.add(scrollBar, BorderLayout.SOUTH);
      selection = new Selection(null);
    }
    else
    {
      Border empty = new EmptyBorder(0,0,0,0);
      jspView.setBorder(empty);
      selection = feature_display.getSelection();
    }
  }
  
  private void createMenus(final JFrame frame, final JScrollPane jspView)
  {
    final JComponent topPanel;
    if(feature_display != null)
      topPanel = new JPanel(new FlowLayout(FlowLayout.LEADING, 0, 0));
    else
    {
      markNewStops.setSelected(false);
      markNewStops.setEnabled(false);
      topPanel = new JMenuBar();
      
      if(frame != null)
        frame.setJMenuBar((JMenuBar)topPanel);
      
      JMenu fileMenu = new JMenu("File");
      topPanel.add(fileMenu);
    
      JMenuItem printImage = new JMenuItem("Save As Image Files (png/jpeg)...");
      printImage.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          PrintVCFview part = new PrintVCFview(VCFview.this);
          part.print();
        }
      });
      fileMenu.add(printImage);
      
      JMenuItem printPS = new JMenuItem("Print...");
      printPS.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          PrintVCFview part = new PrintVCFview(VCFview.this);
          part.validate();
          part.doPrintActions();
        }
      });
      fileMenu.add(printPS);
      

      JMenuItem close = new JMenuItem("Close");
      fileMenu.add(close);
      close.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          VCFview.this.setVisible(false);
          Component comp = VCFview.this;
          
          while( !(comp instanceof JFrame) )
            comp = comp.getParent();
          ((JFrame)comp).dispose();
        } 
      });
      
      JButton zoomIn = new JButton("-");
      Insets ins = new Insets(1,1,1,1);
      zoomIn.setMargin(ins);
      zoomIn.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          setZoomLevel((int) (VCFview.this.nbasesInView * 1.1));
        }
      });
      topPanel.add(zoomIn);

      JButton zoomOut = new JButton("+");
      zoomOut.setMargin(ins);
      zoomOut.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          setZoomLevel((int) (VCFview.this.nbasesInView * .9));
        }
      });
      topPanel.add(zoomOut);
    }
    
    final JComboBox combo = new JComboBox(vcfReaders[0].getSeqNames());
    combo.setEditable(true);
    JTextComponent editor = (JTextComponent) combo.getEditor().getEditorComponent();
    editor.setDocument(new AutoCompleteComboDocument(combo));
    
    if(vcfReaders[0].getSeqNames().length > 1)
      combo.addItem("Combine References");
    
    if(chr == null)
      this.chr = vcfReaders[0].getSeqNames()[0];

    combo.setSelectedItem(this.chr);
    combo.setMaximumRowCount(20);
    
    combo.addItemListener(new ItemListener()
    {
      public void itemStateChanged(ItemEvent e)
      {
        if(combo.getSelectedItem().equals("Combine References"))
          concatSequences = true;
        else 
        {
          VCFview.this.chr = (String) combo.getSelectedItem();
          concatSequences = false;
        }
        repaint();
      }
    });
    topPanel.add(combo);
    if(topPanel instanceof JPanel)
      vcfPanel.add(topPanel, BorderLayout.NORTH);
    
    // auto hide top panel
    final JCheckBox buttonAutoHide = new JCheckBox("Hide", true);
    buttonAutoHide.setToolTipText("Auto-Hide");
    topPanel.add(buttonAutoHide);
    final MouseMotionListener mouseMotionListener = new MouseMotionListener()
    {
      public void mouseDragged(MouseEvent event)
      {
        handleCanvasMouseDrag(event);
      }
      
      public void mouseMoved(MouseEvent e)
      {
        findVariantAtPoint(e.getPoint());

        int thisHgt = HEIGHT;
        if (thisHgt < 5)
          thisHgt = 15;

        int y = (int) (e.getY() - jspView.getViewport().getViewRect().getY());
        if (y < thisHgt)
          topPanel.setVisible(true);
        else
        {
          if (buttonAutoHide.isSelected())
            topPanel.setVisible(false);
        }

      }
    };
    addMouseMotionListener(mouseMotionListener);

    
    // popup menu
    popup = new JPopupMenu();
    
    JMenuItem addVCFMenu = new JMenuItem("Add VCF ...");
    addVCFMenu.addActionListener(new ActionListener() 
    {
      public void actionPerformed(ActionEvent e)
      {
        FileSelectionDialog fileSelection = new FileSelectionDialog(
            null, true, "VCFview", "VCF");
        List<String> vcfFileList = fileSelection.getFiles(VCFFILE_SUFFIX);
        vcfFiles.addAll(vcfFileList);

        int count = vcfFileList.size();
        int oldSize = vcfReaders.length;
        
        AbstractVCFReader[] trTmp = new AbstractVCFReader[count + vcfReaders.length];
        System.arraycopy(vcfReaders, 0, trTmp, 0, vcfReaders.length);
        vcfReaders = trTmp;
        
        String[] hdTmp = new String[count + vcfReaders.length];
        System.arraycopy(header, 0, hdTmp, 0, header.length);
        header = hdTmp;
        
        for (int i = 0; i < vcfFileList.size(); i++)
          header[i+oldSize] = readHeader(vcfFileList.get(i), i+oldSize);
        
        for(int i=0; i<vcfFileList.size(); i++)
          addToViewMenu(i+oldSize);

        setDisplay();
        repaint();
        jspView.revalidate();
      }
    });
    popup.add(addVCFMenu);
    popup.add(vcfFilesMenu);
    
    for(int i=0; i<vcfFiles.size(); i++)
      addToViewMenu(i);
    
    popup.addSeparator();
    

    markNewStops.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        if(!markNewStops.isSelected())
          markAsNewStop = false;
        repaint();
      }
    });
    popup.add(markNewStops);
    
    
    final JMenuItem byQuality = new JMenuItem("Filter ...");
    byQuality.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        new VCFFilter(VCFview.this);
      }
    });
    popup.add(byQuality);
    
    final JMenu colourBy = new JMenu("Colour By");
    popup.add(colourBy);
    ButtonGroup group = new ButtonGroup();
    final JRadioButtonMenuItem colByAlt   = new JRadioButtonMenuItem("Variant");
    colByAlt.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        if(colByAlt.isSelected())
          colourScheme = 0;
        repaint();
      }
    });
    colourBy.add(colByAlt);
    
    final JRadioButtonMenuItem colBySyn   = new JRadioButtonMenuItem("Synonymous/Non-synonymous");
    colBySyn.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        if(colBySyn.isSelected())
          colourScheme = 1;
        repaint();
      }
    });
    colourBy.add(colBySyn);
    
    final JRadioButtonMenuItem colByScore = new JRadioButtonMenuItem("Score");
    colByScore.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        if(colByScore.isSelected())
          colourScheme = 2;
        repaint();
      }
    });
    colourBy.add(colByScore);
    
    group.add(colByAlt);
    group.add(colBySyn);
    group.add(colByScore);
    colByAlt.setSelected(true);
    
    popup.addSeparator();

    if (feature_display != null)
    {
      final JMenu create = new JMenu("Create");
      final JMenuItem createTab = new JMenuItem(
          "Features from variants");
      popup.add(create);
      create.add(createTab);
      createTab.addActionListener(new ActionListener()
      {
        public void actionPerformed(ActionEvent e)
        {
          Container f = getVcfContainer();
          try
          {
            f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
            IOUtils.createFeatures(VCFview.this, entryGroup);
          }
          finally
          {
            f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
          }
        }
      });
    }

    final JMenu export = new JMenu("Write");
    popup.add(export);
    
    final JMenuItem exportVCF = new JMenuItem("Filtered VCF");
    exportVCF.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.export(vcfFiles, VCFview.this);
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    export.add(exportVCF);
    export.add(new JSeparator());
    
    final JMenuItem exportFastaSelected = new JMenuItem("FASTA of selected feature(s) ...");
    exportFastaSelected.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.exportFasta(VCFview.this, selection.getAllFeatures(), false, null);
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    export.add(exportFastaSelected);
    
    final JMenuItem exportFasta = new JMenuItem("FASTA of selected base range ...");
    exportFasta.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.exportFastaByRange(VCFview.this, selection, false, null);
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    export.add(exportFasta);
    
    final JMenu view = new JMenu("View");
    popup.add(view);
    final JMenuItem viewFastaSelected = new JMenuItem("FASTA of selected feature(s) ...");
    viewFastaSelected.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.exportFasta(VCFview.this, selection.getAllFeatures(), true, null);
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    view.add(viewFastaSelected);
    
    final JMenuItem viewFasta = new JMenuItem("FASTA of selected base range ...");
    viewFasta.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.exportFastaByRange(VCFview.this, selection, true, null);
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    view.add(viewFasta);
    
    JMenu graph = new JMenu("Graph");
    popup.add(graph);
    
    final JCheckBoxMenuItem graphSNP = new JCheckBoxMenuItem("SNP");
    final JCheckBoxMenuItem graphDP = new JCheckBoxMenuItem("Depth (DP)");
    graph.add(graphSNP);
    graphSNP.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        graphPanel.setVisible(graphSNP.isSelected());
        graphDP.setSelected(false);
        graphPanel.setType(0);
        graphPanel.repaint();
      }
    });
    
    graph.add(graphDP);
    graphDP.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        graphPanel.setVisible(graphDP.isSelected());
        graphSNP.setSelected(false);
        graphPanel.setType(1);
        graphPanel.repaint();
      }
    });
    
    final JMenuItem snpOverview = new JMenuItem("Overview for selected features");
    popup.add(snpOverview);
    snpOverview.addActionListener(new ActionListener()
    {
      public void actionPerformed(ActionEvent e)
      {
        Container f = getVcfContainer();
        try
        {
          f.setCursor(new Cursor(Cursor.WAIT_CURSOR));
          IOUtils.countVariants(VCFview.this, selection.getAllFeatures());
        }
        catch (IOException e1)
        {
          JOptionPane.showMessageDialog(null, e1.getMessage());
        }
        finally
        {
          f.setCursor(new Cursor(Cursor.DEFAULT_CURSOR));
        }
      }
    });
    
    final JCheckBoxMenuItem labels = new JCheckBoxMenuItem("Show Labels", showLabels);
    labels.addActionListener(new ActionListener(){
      public void actionPerformed(ActionEvent e)
      {
        showLabels = labels.isSelected();
        repaint();
      }
    });
    popup.add(new JSeparator());
    popup.add(labels);
  }
  
  
  private void addToViewMenu(final int thisBamIndex)
  {
    final JCheckBoxMenuItem cbBam = new JCheckBoxMenuItem(
        getLabel(thisBamIndex), true);
    vcfFilesMenu.add(cbBam);
    cbBam.addActionListener(new ActionListener()
    {
      public void actionPerformed(ActionEvent e)
      {
        if(cbBam.isSelected())
          hideVcfList.remove(new Integer(thisBamIndex));
        else
          hideVcfList.add(new Integer(thisBamIndex));
        repaint();
      } 
    });
  }

  private static EntryGroup getReference(String reference)
  {
    EntryGroup entryGroup = new SimpleEntryGroup();
    final Document entry_document = DocumentFactory.makeDocument(reference);
    final EntryInformation artemis_entry_information =
      Options.getArtemisEntryInformation();

    final uk.ac.sanger.artemis.io.Entry new_embl_entry =
      EntryFileDialog.getEntryFromFile(null, entry_document,
                                       artemis_entry_information,
                                       false);
    if(new_embl_entry != null) // the read failed
    {
      Entry entry = null;
      Bases bases = null;
      try
      {
        if (entryGroup.getSequenceEntry() != null)
          bases = entryGroup.getSequenceEntry().getBases();
        if (bases == null)
        {
          entry = new Entry(new_embl_entry);
          bases = entry.getBases();
        }
        else
          entry = new Entry(bases, new_embl_entry);
        entryGroup.add(entry);
      }
      catch (OutOfRangeException e)
      {
        new MessageDialog(null, "read failed: one of the features in "
            + reference + " has an out of range " + "location: "
            + e.getMessage());
      }
      catch (NoSequenceException e)
      {
        // TODO Auto-generated catch block
        e.printStackTrace();
      }
    }
    return entryGroup;
  }
  
  /**
   * Test and download if on a http server
   * @param fileName
   * @return
   */
  private String testForURL(String fileName, boolean isBCF)
  {
    if(!fileName.startsWith("http:") && !fileName.startsWith("ftp:"))
      return fileName;

    return download(fileName+".tbi", ".tbi");
  }
  
  protected String download(String f, String suffix)
  {
    try
    {
      final URL urlFile = new URL(f);
      InputStream is = urlFile.openStream();

      // Create temp file.
      String name = urlFile.getFile();
      int ind = name.lastIndexOf('/');
      if(ind > -1)
        name = name.substring(ind+1);
      File bcfFile = File.createTempFile(name.replaceAll("[\\/\\s]", "_"), suffix);
      
      bcfFile.deleteOnExit();

      FileOutputStream out = new FileOutputStream(bcfFile);
      int c;
      while ((c = is.read()) != -1)
        out.write(c);
      out.flush();
      out.close();
      is.close();
      return bcfFile.getAbsolutePath();
    }
    catch(IOException ioe)
    {
      JOptionPane.showMessageDialog(null, 
          "Problem downloading\n"+f, 
          "Problem", JOptionPane.WARNING_MESSAGE);
    }
    return null;
  }
  
  /**
   * Read the vcf header
   * @param fileName
   * @return
   */
  private String readHeader(String fileName, int index)
  {
    StringBuffer buff = new StringBuffer();
    buff.append(fileName+"\n");
    try
    {
      if(IOUtils.isBCF(fileName))
      {
        vcfReaders[index] = new BCFReader(fileName);
        String hdr = ((BCFReader)vcfReaders[index]).headerToString();
        if(hdr.indexOf("VCFv4") > -1)
          vcfReaders[index].setVcf_v4(true);
        return hdr;
      }

      String indexfileName = testForURL(fileName, false);
      BlockCompressedInputStream is;
      if(fileName.startsWith("http")|| fileName.startsWith("ftp"))
      {
        URL url = new URL(fileName);
        if(fileName.startsWith("ftp"))
          vcfReaders[index] = new TabixReader(indexfileName.substring(0, indexfileName.length()-4), new FTPSeekableStream(url));
        else
          vcfReaders[index] = new TabixReader(indexfileName.substring(0, indexfileName.length()-4), url);
        is = new BlockCompressedInputStream(url);
      }
      else
      {
        vcfReaders[index] = new TabixReader(fileName);
        is = new BlockCompressedInputStream(new FileInputStream(fileName));
      }

      String line;
      while( (line = TabixReader.readLine(is) ) != null )
      {
        if(!line.startsWith("##"))
          break;
        
        if(line.indexOf("VCFv4") > -1)
          vcfReaders[index].setVcf_v4(true);
        buff.append(line+"\n");
      }
      is.close();
    }
    catch (IOException e)
    {
      e.printStackTrace();
    }
    
    return buff.toString();
  }
  
  /**
   * Set the number of bases being displayed
   * @param nbasesInView
   */
  private void setZoomLevel(final int nbasesInView)
  {
    int startValue = scrollBar.getValue();
    this.nbasesInView = nbasesInView;
    float pixPerBase = getPixPerBaseByWidth(); 
    this.nbasesInView = (int)(getWidth()/pixPerBase);
    
    if(scrollBar != null)
    {
      scrollBar.setValues(startValue, nbasesInView, 1, seqLength);
      scrollBar.setUnitIncrement(nbasesInView/20);
      scrollBar.setBlockIncrement(nbasesInView);
    }
  }
  
  public String getToolTipText()
  {
    if(mouseVCF == null)
      return null;

    String msg = 
           "Seq: "+mouseVCF.getChrom()+"\n";
    msg += "Pos: "+mouseVCF.getPos()+"\n";
    msg += "ID:  "+mouseVCF.getID()+"\n";
    msg += "Variant: "+mouseVCF.getRef()+" -> "+mouseVCF.getAlt().toString()+"\n";
    msg += "Qual: "+mouseVCF.getQuality()+"\n";
    String pl;
    if((pl = mouseVCF.getFormatValue("PL")) != null && pl.split(",").length > 1)
      msg += "Genotype likelihood (PL): "+pl+"\n";
    return msg;
  }
  
  
  
  /**
   * For VCF files with multiple references sequences, calculate
   * the offset from the start of the concatenated sequence for 
   * a given reference.
   * @param refName
   * @return
   */
  protected int getSequenceOffset(String refName)
  {
    if(!concatSequences)
      return 0;
    
    if(offsetLengths == null)
    {   
      String[] contigs = vcfReaders[0].getSeqNames();
      FeatureVector features = entryGroup.getAllFeatures();
      offsetLengths = new Hashtable<String, Integer>(contigs.length);
      for(int i=0; i<contigs.length; i++)
      {
        FeatureContigPredicate predicate = new FeatureContigPredicate(contigs[i]);
        for(int j=0; j<features.size(); j++)
        {
          if(predicate.testPredicate(features.elementAt(j)))
          {
            offsetLengths.put(contigs[i], features.elementAt(j).getFirstBase()-1);
            break;
          }
        }
      }
      
      if(offsetLengths.size() != contigs.length)
      {
        System.err.println("Number of contigs found : "+offsetLengths.size() +
                         "\nNumber of contigs in VCF: "+contigs.length);
        JOptionPane.showMessageDialog(this, 
            "There is a problem matching the reference sequences\n"+
            "to the names in the VCF file. This may mean the labels\n"+
            "on the reference features do not match those in the in\n"+
            "the VCF file.", 
            "Problem Found", JOptionPane.WARNING_MESSAGE);
        concatSequences = false;
        return 0;
      }
    }
    return offsetLengths.get(refName);
  }
  
  public void repaint()
  {
    super.repaint();
    if(graphPanel != null && graphPanel.isVisible())
      graphPanel.repaint();
  }
  
  protected void paintComponent(Graphics g)
  {
    super.paintComponent(g);
    
    Graphics2D g2d = (Graphics2D)g;
    mouseVCF = null;

    float pixPerBase = getPixPerBaseByWidth();
    int start = getBaseAtStartOfView();
    int end   = start+nbasesInView;
    
    drawSelectionRange((Graphics2D)g, pixPerBase, start, end);

    FeatureVector features = getCDSFeaturesInRange(start, end);
    for (int i = 0; i < vcfReaders.length; i++)
    {
      if(hideVcfList.contains(i))
        continue;
      
      if(concatSequences) 
      {
        String[] contigs = vcfReaders[0].getSeqNames();
        for(int j=0; j<contigs.length; j++)
        {