// Crossover applet
// ----------------
// Educational demo program showing the relationship between recombination
// fraction and map distance between two loci on a chromosome.
//
// Author:
//   Paul O. Lewis                      
//   Department of Ecology and         
//      Evolutionary Biology        
//   The University of Connecticut    
//   75 N. Eagleville Road, Unit 3043
//   Storrs, CT 06269-3043
//
// Tel: (860) 486-2069
// Fax: (860) 486-6364
// E-mail: paul.lewis@uconn.edu
// http://hydrodictyon.eeb.uconn.edu/people/plewis/
//
// Copyright (C) 1999 by Paul O. Lewis
//
// While now modified almost beyond recognition, this applet grew out of
// playing with the Graph.java applet created by Jim Hagen and available
// through the web site java.sun.com
//
// Permission to use, copy, modify, and distribute this software
// and its documentation for NON-COMMERCIAL purposes and
// without fee is hereby granted.

import java.applet.Applet;
import java.awt.event.*;
import java.awt.*;
import java.io.*;
import java.util.*;
import java.net.*;

class Chromatid
{
   Color color;
   int xleft;
   int xright;
   int y;
   int y1;
   int locusA;
   int locusB;
   String alleleA;
   String alleleB;
   Vector crossoverPoints;

   boolean myA;
   boolean myB;

   final int radius = 2;

   public Chromatid( Color c, int xl, int xr, int yme, int yother1, int xA, int xB, String allA, String allB )
   {
      color = c;
      xleft = xl;
      xright = xr;
      y = yme;
      y1 = yother1;
      locusA = xA;
      locusB = xB;
      alleleA = allA;
      alleleB = allB;
      myA = true;
      myB = true;
      crossoverPoints = new Vector(2, 2);
   }

   public boolean IsMyA() {
      return myA;
   }

   public boolean IsMyB() {
      return myB;
   }

   public void SetLocusA( int k ) {
      locusA = k;
   }

   public void SetLocusB( int k ) {
      locusB = k;
   }

   public void ResetCrossOverPoints() {
      myA = true;
      myB = true;
      crossoverPoints.removeAllElements();
   }

   public void AddCrossOverPoint( double x ) {
      Double d = new Double(x);
      crossoverPoints.addElement(d);
   }

   public void UpdateConstitutionFlags()
   {
    if( crossoverPoints.isEmpty() ) {
      myA = true;
      myB = true;
    }
    else {
      int crossovers = crossoverPoints.size();
      int xstart = xleft;
      boolean atOtherY = false;
      for( int i = 0; i < crossovers; i++ )
      {
        // xopoint is the position of the next crossover point
        // as a fraction of the chromatid's length
        Double d = (Double)crossoverPoints.elementAt(i);
    		double xopoint = d.doubleValue();
        int xend = xleft + (int)( xopoint * ( xright - xleft ) );

        // ignore crossovers that are too close to previous crossover to draw
        if( xend < xstart + radius )
          continue;

        // ignore crossovers if they are right on top of one of the loci
        int posA = xleft + locusA;
        int posB = xleft + locusB;
        if( (xend - radius <= posA) && (xend + radius >= posA) )
          continue;
        if( (xend - radius <= posB) && (xend + radius >= posB) )
          continue;

        if( atOtherY ) {
          // identify locus A if it lies in this section
          if( posA >= xstart && posA < xend - radius ) {
            myA = false;
          }

          // identify locus B if it lies in this section
          if( posB >= xstart && posB < xend - radius ) {
            myB = false;
          }

          atOtherY = false;
        }
        else {
          // identify locus A if it lies in this section
          if( posA >= xstart && posA < xend - radius ) {
            myA = true;
          }

          // identify locus B if it lies in this section
          if( posB >= xstart && posB < xend - radius ) {
            myB = true;
          }

          atOtherY = true;
        }
        xstart = xend + radius + 2;
      }

      if( atOtherY ) {

        // identify locus A if it lies in this section
        int posA = xleft + locusA;
        if( posA >= xstart && posA < xright ) {
          myA = false;
        }

        // identify locus B if it lies in this section
        int posB = xleft + locusB;
        if( posB >= xstart && posB < xright ) {
          myB = false;
        }

      }
      else {
        // identify locus A if it lies in this section
        int posA = xleft + locusA;
        if( posA >= xstart && posA < xright ) {
          myA = true;
        }

        // place locus B if it lies in this section
        int posB = xleft + locusB;
        if( posB >= xstart && posB < xright ) {
          myB = true;
        }
      }
    }
	}

	public void paint( Graphics g )
  {
		g.setColor( color );
    if( crossoverPoints.isEmpty() ) {
  		g.drawLine( xleft, y, xright, y );
	  	g.drawString( alleleA, xleft + locusA, y-radius );
		  g.drawString( alleleB, xleft + locusB, y-radius );
  		g.fillOval( xleft+locusA-radius, y-radius, 2*radius, 2*radius );
	  	g.fillOval( xleft+locusB-radius, y-radius, 2*radius, 2*radius );
    }
    else {
      int crossovers = crossoverPoints.size();
      int xstart = xleft;
      boolean atOtherY = false;
      for( int i = 0; i < crossovers; i++ )
      {
        // xopoint is the position of the next crossover point
        // as a fraction of the chromatid's length
        Double d = (Double)crossoverPoints.elementAt(i);
    		double xopoint = d.doubleValue();
        int xend = xleft + (int)( xopoint * ( xright - xleft ) );

        // ignore crossovers that are too close to previous crossover to draw
        if( xend < xstart + radius )
          continue;

        // ignore crossovers if they are right on top of one of the loci
        int posA = xleft + locusA;
        int posB = xleft + locusB;
        if( (xend - radius <= posA) && (xend + radius >= posA) )
          continue;
        if( (xend - radius <= posB) && (xend + radius >= posB) )
          continue;

        if( atOtherY ) {
      		g.drawLine( xstart, y1, xend - radius, y1 );
      		g.drawLine( xend - radius, y1, xend + 2*radius, y );

          // identify locus A if it lies in this section
          if( posA >= xstart && posA < xend - radius ) {
      	  	g.drawString( alleleA, xleft + locusA, y1 - radius );
        		g.fillOval( xleft + locusA - radius, y1 - radius, 2*radius, 2*radius );
          }

          // identify locus B if it lies in this section
          if( posB >= xstart && posB < xend - radius ) {
      		  g.drawString( alleleB, xleft + locusB, y1 - radius );
      	  	g.fillOval( xleft + locusB - radius, y1 - radius, 2*radius, 2*radius );
          }

          atOtherY = false;
        }
        else {
      		g.drawLine( xstart, y, xend - radius, y );
      		g.drawLine( xend - radius, y, xend + 2*radius, y1 );

          // identify locus A if it lies in this section
          if( posA >= xstart && posA < xend - radius ) {
      	  	g.drawString( alleleA, xleft + locusA, y - radius );
        		g.fillOval( xleft + locusA - radius, y - radius, 2*radius, 2*radius );
          }

          // identify locus B if it lies in this section
          if( posB >= xstart && posB < xend - radius ) {
      		  g.drawString( alleleB, xleft + locusB, y - radius );
      	  	g.fillOval( xleft + locusB - radius, y - radius, 2*radius, 2*radius );
          }

          atOtherY = true;
        }
        xstart = xend + radius + 2;
      }

      if( atOtherY ) {
        g.drawLine( xstart, y1, xright, y1 );

        // identify locus A if it lies in this section
        int posA = xleft + locusA;
        if( posA >= xstart && posA < xright ) {
          g.drawString( alleleA, xleft + locusA, y1 - radius );
          g.fillOval( xleft + locusA - radius, y1 - radius, 2*radius, 2*radius );
        }

        // identify locus B if it lies in this section
        int posB = xleft + locusB;
        if( posB >= xstart && posB < xright ) {
          g.drawString( alleleB, xleft + locusB, y1 - radius );
          g.fillOval( xleft + locusB - radius, y1 - radius, 2*radius, 2*radius );
        }

      }
      else {
        g.drawLine( xstart, y, xright, y );

        // identify locus A if it lies in this section
        int posA = xleft + locusA;
        if( posA >= xstart && posA < xright ) {
          g.drawString( alleleA, xleft + locusA, y - radius );
          g.fillOval( xleft + locusA - radius, y - radius, 2*radius, 2*radius );
        }

        // place locus B if it lies in this section
        int posB = xleft + locusB;
        if( posB >= xstart && posB < xright ) {
          g.drawString( alleleB, xleft + locusB, y - radius );
          g.fillOval( xleft + locusB - radius, y - radius, 2*radius, 2*radius );
        }

      }
    }
	}
};

class ChromoPanel extends Canvas implements MouseListener, MouseMotionListener
{
	final int width = 200;
	final int height = 200;

   Chromatid one_a;
   Chromatid one_b;
   Chromatid two_a;
   Chromatid two_b;

   int nAB;
   int nab;
   int nAb;
   int naB;

   double locusA = 0.3;
   double locusB = 0.8;

	Font normalFont = null;

	Image offimg = null;
	Graphics offg = null;
	boolean first_update = true;

	public ChromoPanel() {
		setSize( width, height );

      // create chromatids, specifying
      //   color of chromatid
      //   x coordinate of left end of chromatid
      //   x coordinate of right end of chromatid
      //   y coordinate of chromatid
      //   y coordinate of one non-homologous chromatid
      //   x coordinate of the A locus
      //   x coordinate of the B locus
      int xleft   = 10;
      int xright  = width - 10;
      int y       = 2*height/8;
      int yother  = 5*height/8;
      int xA      = (int)(locusA * (double)( width - 20 ) );
      int xB      = (int)(locusB * (double)( width - 20 ) );
      one_a = new Chromatid( Color.blue, xleft, xright, y, yother, xA, xB, "A", "B" );

      xleft   = 10;
      xright  = width - 10;
      y       = 3*height/8;
      yother =  6*height/8;
      one_b = new Chromatid( Color.blue, xleft, xright, y, yother, xA, xB, "A", "B" );

      xleft   = 10;
      xright  = width - 10;
      y       = 5*height/8;
      yother  = 2*height/8;
      two_a = new Chromatid( Color.red, xleft, xright, y, yother, xA, xB, "a", "b" );

      xleft   = 10;
      xright  = width - 10;
      y       = 6*height/8;
      yother  = 3*height/8;
      two_b = new Chromatid( Color.red, xleft, xright, y, yother, xA, xB, "a", "b" );

      nAB = 0;
      nab = 0;
      nAb = 0;
      naB = 0;
	}

  public void ResetCounts() {
      nAB = 0;
      nab = 0;
      nAb = 0;
      naB = 0;
      one_a.ResetCrossOverPoints();
      one_b.ResetCrossOverPoints();
      two_a.ResetCrossOverPoints();
      two_b.ResetCrossOverPoints();
      repaint();
  }

  public void GetCounts( Label AB, Label ab, Label Ab, Label aB, Label rf ) {
    AB.setText( Integer.toString(nAB) );
    ab.setText( Integer.toString(nab) );
    Ab.setText( Integer.toString(nAb) );
    aB.setText( Integer.toString(naB) );
    double d = 0.0;
    double total = (double)( nAB + nab + nAb + naB );
    if( total > 0.0 ) {
      d = (double)( nAb + naB ) / total;
      rf.setText( Double.toString(d) );
    }
    else
      rf.setText( "*****" );
  }

  public void SetFirstLocusPosition( double d ) {
    int xA = (int)(d * (double)( width - 20 ) );
    one_a.SetLocusA(xA);
    one_b.SetLocusA(xA);
    two_a.SetLocusA(xA);
    two_b.SetLocusA(xA);
    repaint();
  }

  public void SetSecondLocusPosition( double d ) {
    int xB  = (int)(d * (double)( width - 20 ) );
    one_a.SetLocusB(xB);
    one_b.SetLocusB(xB);
    two_a.SetLocusB(xB);
    two_b.SetLocusB(xB);
    repaint();
  }

  public void UpdateCounts() {
    one_a.UpdateConstitutionFlags();
    one_b.UpdateConstitutionFlags();
    two_a.UpdateConstitutionFlags();
    two_b.UpdateConstitutionFlags();

    if( one_a.IsMyA() && one_a.IsMyB() ) {
      nAB++;
    }
    else if( one_a.IsMyA() && !one_a.IsMyB() ) {
      nAb++;
    }
    else if( !one_a.IsMyA() && one_a.IsMyB() ) {
      naB++;
    }
    else if( !one_a.IsMyA() && !one_a.IsMyB() ) {
      nab++;
    }

    if( one_b.IsMyA() && one_b.IsMyB() ) {
      nAB++;
    }                 else if( one_b.IsMyA() && !one_b.IsMyB() ) {
      nAb++;
    }
    else if( !one_b.IsMyA() && one_b.IsMyB() ) {
      naB++;
    }
    else if( !one_b.IsMyA() && !one_b.IsMyB() ) {
      nab++;
    }

    if( two_a.IsMyA() && two_a.IsMyB() )
      nab++;
    else if( two_a.IsMyA() && !two_a.IsMyB() )
      naB++;
    else if( !two_a.IsMyA() && two_a.IsMyB() )
      nAb++;
    else if( !two_a.IsMyA() && !two_a.IsMyB() )
      nAB++;

    if( two_b.IsMyA() && two_b.IsMyB() )
      nab++;
    else if( two_b.IsMyA() && !two_b.IsMyB() )
      naB++;
    else if( !two_b.IsMyA() && two_b.IsMyB() )
      nAb++;
    else if( !two_b.IsMyA() && !two_b.IsMyB() )
      nAB++;
  }

  public double GetNextExponential( Random rng, double lambda ) {
      // pick an exponential random variable based on lambda
      double exprn = 0.0;
      while( exprn <= 0.0 || exprn > 1.0 )
        exprn = 1.0 - rng.nextDouble();
      exprn = -Math.log(exprn); // was dividing by lambda here;
      return exprn;
  }

  public void Simulate( Random rng, double lambda ) {

    // pick exponential random variables to determine
    // crossover points
    double currPos1 = 0.0; // for chromatids one_a and two_a
    double currPos2 = 0.0; // for chromatids one_b and two_b

    // resetting counts each time for testing purposes
    //ResetCounts();

    // counts accumulate with each simulation (normal procedure)
    one_a.ResetCrossOverPoints();
    one_b.ResetCrossOverPoints();
    two_a.ResetCrossOverPoints();
    two_b.ResetCrossOverPoints();

    for(;;) {
      double exprn = GetNextExponential( rng, lambda );

      // place a crossover at a distance exprn from
      // left end of chromatids one_a and two_a
      currPos1 += exprn;
      if( currPos1 >= 1.0 )
        break;

      one_a.AddCrossOverPoint( currPos1 );
      two_a.AddCrossOverPoint( currPos1 );

      exprn = GetNextExponential( rng, lambda );

      // place a crossover at a distance exprn from
      // left end of chromatids one_b and two_b
      currPos2 += exprn;
      if( currPos2 >= 1.0 )
        break;

      one_b.AddCrossOverPoint( currPos2 );
      two_b.AddCrossOverPoint( currPos2 );
    }

    repaint();
  }

	public void update( Graphics g ) {
		if( first_update ) {
			offimg = createImage( width, height );
			offg = offimg.getGraphics();
			normalFont = new Font( "Ariel", Font.BOLD, 10 );
			first_update = false;
		}
		offg.setColor( Color.lightGray );
		offg.fillRect( 0, 0, width, height );

     // paint chromosomes
      one_a.paint(offg);
      one_b.paint(offg);
      two_a.paint(offg);
      two_b.paint(offg);

		paint(g);
	}

	public void paint( Graphics g ) {
		if( first_update )
			repaint();
		else
			g.drawImage( offimg, 0, 0, this );
	}

    public Dimension getPreferredSize() {
        return new Dimension( width, height );
    }

	public void mouseMoved( MouseEvent e ) {}
	public void mouseEntered( MouseEvent e ) {}
	public void mouseExited( MouseEvent e ) {}
	public void mouseClicked( MouseEvent e ) {}

	public void mousePressed( MouseEvent e ) {
		int curr_x = e.getX();
		int curr_y = e.getY();
      // do stuff
	}

	public void mouseReleased( MouseEvent e ) {
		int curr_x = e.getX();
		int curr_y = e.getY();
      // do stuff
		repaint();
	}

	public void mouseDragged( MouseEvent e ) {
		int curr_x = e.getX();
		int curr_y = e.getY();
      // do stuff
		repaint();
	}
};

public class CrossOver extends Applet implements WindowListener, ActionListener, ItemListener, MouseListener, MouseMotionListener
{
  Label num_AB;
  Label num_ab;
  Label num_Ab;
  Label num_aB;
  Label recomb_frac;
	ChromoPanel chromoPanel = null;
	Button simButton = null;
	Button resetButton = null;
	Choice centiMorgans = null;
	Choice firstLocus = null;
	Choice secondLocus = null;
	boolean first_update = true;
	Random rng;
	Point locusA1;
	Point locusA2;
	Point locusB1;
	Point locusB2;

	public CrossOver() {
	rng = new Random();
    locusA1 = new Point();
    locusA2 = new Point();
    locusB1 = new Point();
    locusB2 = new Point();
	}

	public void setAppletFrame( Frame f ) {
		f.addWindowListener(this);
	}

	public void windowOpened( WindowEvent e ) {}
	public void windowClosing( WindowEvent e ) { System.exit(0); }
	public void windowClosed( WindowEvent e ) {}
	public void windowIconified( WindowEvent e ) {}
	public void windowDeiconified( WindowEvent e ) {}
	public void windowActivated( WindowEvent e ) {}
	public void windowDeactivated( WindowEvent e ) {}

	public void actionPerformed( ActionEvent e ) {
		if( e.getSource() == simButton ) {
			Simulate();
		}
		else if( e.getSource() == resetButton ) {
      chromoPanel.ResetCounts();
      chromoPanel.GetCounts( num_AB, num_ab, num_Ab, num_aB, recomb_frac );
		}
	}

	public void itemStateChanged( ItemEvent e ) {
    if( e.getSource() == firstLocus ) {
      double d = Double.valueOf( firstLocus.getSelectedItem() ).doubleValue();
      chromoPanel.SetFirstLocusPosition(d);
    }
    else if( e.getSource() == secondLocus ) {
      double d = Double.valueOf( secondLocus.getSelectedItem() ).doubleValue();
      chromoPanel.SetSecondLocusPosition(d);
    }
	}

	public void mouseClicked( MouseEvent e ) {}
	public void mousePressed( MouseEvent e ) {
    Point clickPoint = e.getPoint();
  }
	public void mouseReleased( MouseEvent e ) {
		// do stuff
	}
	public void mouseEntered( MouseEvent e ) {}
	public void mouseExited( MouseEvent e ) {}
	public void mouseDragged( MouseEvent e ) {}
	public void mouseMoved( MouseEvent e ) {}

	public void Simulate() {
    // compute lambda from centiMorgans Choice object
		String ss = centiMorgans.getSelectedItem();
		double cM = Double.valueOf(ss).doubleValue();
    double lambda = cM / 100.0;
    chromoPanel.Simulate( rng, lambda );
    chromoPanel.UpdateCounts();
    chromoPanel.GetCounts( num_AB, num_ab, num_Ab, num_aB, recomb_frac );
	}

	public void init() {
		setLayout( new BorderLayout() );

		Panel p1 = new Panel();
		chromoPanel = new ChromoPanel();
		chromoPanel.addMouseListener(this);
		chromoPanel.addMouseListener(chromoPanel);
		chromoPanel.addMouseMotionListener(this);
		chromoPanel.addMouseMotionListener(chromoPanel);
		p1.add(chromoPanel);
		add( "Center", p1 );

		Panel p2 = new Panel();
		simButton = new Button( "Simulate" );
		simButton.addActionListener(this);
		p2.add(simButton);
		resetButton = new Button( "Reset" );
		resetButton.addActionListener(this);
		p2.add(resetButton);
		add( "South", p2 );

		Panel p3 = new Panel();
    p3.setLayout( new GridLayout( 8, 1 ) );

    // centimorgans choice
		centiMorgans = new Choice();
		centiMorgans.addItem( "100" );
		centiMorgans.addItem( "200" );
		centiMorgans.addItem( "500" );
		centiMorgans.addItem( "1000" );
    Panel p3a = new Panel();
		p3a.add( new Label( "centimorgans:", Label.RIGHT ) );
		p3a.add( centiMorgans );
    p3.add(p3a);

    // firstLocus choice
		firstLocus = new Choice();
		firstLocus.addItem( "0.1" );
		firstLocus.addItem( "0.2" );
		firstLocus.addItem( "0.3" );
		firstLocus.addItem( "0.4" );
		firstLocus.addItem( "0.5" );
		firstLocus.addItem( "0.6" );
		firstLocus.addItem( "0.7" );
		firstLocus.addItem( "0.8" );
		firstLocus.addItem( "0.9" );
    firstLocus.select(2);
		firstLocus.addItemListener(this);
    Panel p3b = new Panel();
		p3b.add( new Label( "locus A:", Label.RIGHT ) );
    p3b.add( firstLocus );
    p3.add(p3b);

    // secondLocus choice
		secondLocus = new Choice();
		secondLocus.addItem( "0.1" );
		secondLocus.addItem( "0.2" );
		secondLocus.addItem( "0.3" );
		secondLocus.addItem( "0.4" );
		secondLocus.addItem( "0.5" );
		secondLocus.addItem( "0.6" );
		secondLocus.addItem( "0.7" );
		secondLocus.addItem( "0.8" );
		secondLocus.addItem( "0.9" );
    secondLocus.select(7);
		secondLocus.addItemListener(this);
    Panel p3c = new Panel();
		p3c.add( new Label( "locus B:", Label.RIGHT ) );
    p3c.add( secondLocus );
    p3.add(p3c);

    Panel p3d = new Panel();
		p3d.add( new Label( "No. AB gametes:", Label.RIGHT ) );
    num_AB = new Label( "0", Label.LEFT );
    p3d.add( num_AB );
    p3.add(p3d);

    Panel p3e = new Panel();
		p3e.add( new Label( "No. ab gametes:", Label.RIGHT ) );
    num_ab = new Label( "0", Label.LEFT );
    p3e.add( num_ab );
    p3.add(p3e);

    Panel p3f = new Panel();
		p3f.add( new Label( "No. Ab gametes:", Label.RIGHT ) );
    num_Ab = new Label( "0", Label.LEFT );
    p3f.add( num_Ab );
    p3.add(p3f);

    Panel p3g = new Panel();
		p3g.add( new Label( "No. aB gametes:", Label.RIGHT ) );
    num_aB = new Label( "0", Label.LEFT );
    p3g.add( num_aB );
    p3.add(p3g);

    Panel p3h = new Panel();
		p3h.add( new Label( "Recomb. fraction:", Label.RIGHT ) );
    recomb_frac = new Label( "*****", Label.LEFT );
    p3h.add( recomb_frac );
    p3.add(p3h);

		add( "West", p3 );

		repaint();
	}

	public static void main( String args[] )
	{
		Frame f = new Frame("Crossing Over Demo");
		f.setSize( 500, 300 );
		CrossOver xo = new CrossOver();
		xo.setAppletFrame(f);
		xo.init();
		f.add( "Center", xo );
		f.show();
	}
}