#!/usr/bin/perl -w

#    LACK v 3.1
#    lack30.pl
#    Copyright 2002-2005 Charlie Kim
#
#    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.
#
#    For a copy of the GNU General Public License, write to the Free Software
#    Foundation, Inc., 59 Temple Place, Suite 330, Boston, MA  02111-1307  USA

# This program uses the following modules

# Perl/Tk 800.023  Copyright (c) 1995-1996 Nick Ing-Simmons. 
# http://starbase.neosoft.com/%7Eclaird/comp.lang.perl.tk/ptkFAQ.html

# Statistics::Descriptive

use strict;
use Tk;
use Tk::Label;
use Tk::Button;
use Tk::Checkbutton;
use Tk::Frame;
use Tk::Entry;
use Tk::Radiobutton;
use Tk::Scale;
use Tk::Scrollbar;
use Tk::Text;
use Tk::ErrorDialog;
use Tk::ProgressBar;
use Tk::Balloon;
use Tk::ROText;
use Tk::NoteBook;

use Statistics::Descriptive;

use Getopt::Std;

#use bignum;

use Math::BigInt;
use Math::BigFloat;


our ($opt_w, $opt_f, $opt_a, $opt_i, $opt_r, $opt_o);
getopts('w:f:a:i:r:o:');
my ($wordfile, $fullfile, $analyzedfile, $iter, $raw, $outfile);
$wordfile = $opt_w if $opt_w;
$fullfile = $opt_f if $opt_f;
$analyzedfile = $opt_a if $opt_a;
$outfile = $opt_o if $opt_o;
if ($opt_i) {
    $iter = $opt_i;
}
else { $iter = 1000; }
if ($opt_r) {
    $raw = 1;
}
else {$raw = 0; }

if (!$wordfile || !$fullfile || !$analyzedfile || !$outfile) {
    &lackgui;
}
else { &lackcommand($wordfile,$analyzedfile,$fullfile,$iter,$raw,$outfile); }

sub lackgui {
    my $mw = MainWindow->new(-title=>'LACK 3.1');

    my $data = <<EOF;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=
EOF

    my $image = $mw->Photo(-data => $data);
    $mw->Icon( -image => $image );

    $mw->Label(-text=>'Lexical Analysis by Charlie Kim',
	       )->pack();
    
# Input #
    
    my $inputfr = $mw->Frame(-relief=>'groove',
			     -borderwidth=>2,
			     )->pack(-side=>'top',
				     -anchor=>'nw',
				     -fill=>'both',
				     );
    
    my $wordfile_label = $inputfr->Label(-text=>'Wordlist File',
		                          )->grid(-row=>0,-column=> 0,-sticky=>'e');
    my $wordfile_lab_bal = $mw->Balloon(-state=>'balloon',
                                        -background=>'white');
    my $wordfilehelp = "A line-delimited list of words to search for.\nExample:\niron\nmanganese\nmagnesium\ncalcium\ndivalent";
    $wordfile_lab_bal->attach($wordfile_label,
                              -balloonmsg => $wordfilehelp,
                              );


    my $wordfile;
    my $wordfile_e = $inputfr->Entry(-state=>'normal',
				     -textvariable=> \$wordfile,
				     -width=>30,
				     )->grid(-row=>0,-column=> 1,-sticky=>'w');
    $inputfr->Button(-text=>'Browse',
		     -command=> [ \&selectsinglefile, \$wordfile_e , \$mw ],
		     -borderwidth=>1,
		     -padx=> 0,
		     -pady=> 0,
		     )->grid(-row=>0,-column=> 2,-sticky=>'w');
    
    my $full_label =$inputfr->Label(-text=>'Full Dataset File',
		                    )->grid(-row=>1,-column=> 0,-sticky=>'e');
    my $full_lab_bal = $mw->Balloon(-state=>'balloon',
                                    -background=>'white');
    my $fullhelp = "Full filtered dataset.  Should be identical to the full dataset used for analysis (e.g. in SAM or Cluster).";
    $full_lab_bal->attach($full_label,
                          -balloonmsg => $fullhelp);


    my $annfile;
    my $annfile_e = $inputfr->Entry(-state=>'normal',
				    -textvariable=> \$annfile,
				    -width=>30,
				    )->grid(-row=>1,-column=> 1,-sticky=>'w');
    $inputfr->Button(-text=>'Browse',
		     -command=> [ \&selectsinglefile, \$annfile_e, \$mw ],
		     -borderwidth=>1,
		     -padx=> 0,
		     -pady=> 0,
		     )->grid(-row=>1,-column=> 2,-sticky=>'w');
    
    my $anal_label = $inputfr->Label(-text=>'Significant Genes File',
		                     )->grid(-row=>2,-column=> 0,-sticky=>'e');
    my $anal_lab_bal = $mw->Balloon(-state=>'balloon',
                                    -background=>'white');
    my $analhelp = "The top significant genes generated in an analysis (e.g. SAM or Cluster).\nShould have far fewer entries than the full dataset.  Also known as the significant genes list (SGL).";
    $anal_lab_bal->attach($anal_label,
                          -balloonmsg=>$analhelp);


    my $datafile;
    my $datafile_e = $inputfr->Entry(-state=>'normal',
				     -textvariable=> \$datafile,
				     -width=>30,
				     )->grid(-row=>2,-column=> 1,-sticky=>'w');
    $inputfr->Button(-text=>'Browse',
		     -command=> [ \&selectsinglefile, \$datafile_e, \$mw ],
		     -borderwidth=>1,
		     -padx=> 0,
		     -pady=> 0,
		     )->grid(-row=>2,-column=> 2,-sticky=>'w');
    
    my $statfr = $mw->Frame(-relief=>'groove',
			     -borderwidth=>2,
			     )->pack(-side=>'top',
				     -anchor=>'nw',
				     -fill=>'both',
				     );

    my $stattype = 0;
    $statfr->Label(-text=>"Statistics")->grid(-row=>5,-column=>0,-sticky=>'e');
    my $iter_e;
    my $raw_c;
    my $iter_label;
    my $raw_label;
    my $binbut = $statfr->Radiobutton(-text=> "Binomial",
				      -variable=> \$stattype,
				      -value=> 0,
				      -borderwidth=>0,
				      -command=> [\&modstate,\$iter_e,\$raw_c,\$stattype,\$iter_label,\$raw_label ],
				      )->grid(-row=>5,
					      -column=>1,
					      -sticky=>'w',
					      );
    my $poibut = $statfr->Radiobutton(-text=> "Poisson",
				      -variable=> \$stattype,
				      -value=> 1,
				      -borderwidth=>0,
				      -command=> [\&modstate,\$iter_e,\$raw_c,\$stattype,\$iter_label,\$raw_label ],
				      )->grid(-row=>6,
					      -column=>1,
					      -sticky=>'w',
					      );
    
    
    my $iterations = 1000;
    $iter_label = $statfr->Label(-text=>'Iterations',
#				 -foreground=>'SystemDisabledText',
				 )->grid(-row=>10,
					 -column=>1,
					 -sticky=>'e',
					 );

    # portability ok
    if ($^O =~ /mswin/i) {
	$iter_label->configure(-foreground=>'SystemDisabledText');
    }
    else {
	$iter_label->configure(-foreground=>'grey');
    }


    my $iter_lab_bal = $mw->Balloon(-state=>'balloon',
                                    -background=>'white');
    my $iterhelp = "The number of random datasets to generate.";
    $iter_lab_bal->attach($iter_label,
                          -balloonmsg=>$iterhelp);
    
    $iter_e = $statfr->Entry(-state=>'normal',
			     -textvariable=> \$iterations,
			     -width=>10,
			     -state=>'disabled',
#			     -foreground=>'SystemDisabledText',
#			     -background=>'SystemButtonFace',
			     )->grid(-row=>10,
				     -column=>2,
				     -sticky=>'w',
				     );
# portability ok
    if ($^O =~ /mswin/i) {
	$iter_e->configure(-foreground=>'SystemDisabledText',
			   -background=>'SystemButtonFace',
			   );
    }
    else {
	$iter_e->configure(-foreground=>'grey',
			   -background=>'grey',
			   );
    }
    
    my $rawout = 0;
    $raw_label = $statfr->Label(-text=>"Raw Counts Output",
#				-foreground=>'SystemDisabledText',
				)->grid(-row=>11,-column=>1,-sticky=>'e');

# portability ok
    if ($^O =~ /mswin/i) {
	$raw_label->configure(-foreground=>'SystemDisabledText',
			   );
    }
    else {
	$raw_label->configure(-foreground=>'grey',
			   );
    }

    my $raw_lab_bal = $mw->Balloon(-state=>'balloon',
                                   -background=>'white');
    my $rawhelp = "Include raw tally values from the random datasets in the output.";
    $raw_lab_bal->attach($raw_label,
                         -balloonmsg=>$rawhelp);
    
    
    $raw_c = $statfr->Checkbutton(-variable => \$rawout,
				  -state=>'disabled'
				  )->grid(-row=>11,-column=>2,-sticky=>'w');
    
# Run #
    my $percent_done = 0;
    my $progress = $mw->ProgressBar(-width => 8,
				    -blocks => 100,
				    -gap => 0,
				    -colors => [0, 'darkblue'],
				    -variable => \$percent_done,
				    -borderwidth => 2,
#				    -troughcolor => 'SystemButtonFace',
				    )->pack(-fill => 'x',
					    );

#portability ok
    if ($^O =~ /mswin/i) {
	$progress->configure(-troughcolor=>'SystemButtonFace',
			     );
    }
    else {
	$progress->configure(-troughcolor=>'grey',
			     );
    }
    
# log window
    my $log_f = $mw->Frame(-relief=>'groove',
			   -borderwidth=>2,
			   )->pack(-fill=>'both',
				   -expand=>1);
    my $logwin = $log_f->Scrolled("Text")->pack(-fill=>'both',
						-expand=>1);
    $logwin->configure(-height=>15,
		       -width=>50,
		       -wrap=>'none',
		       -state=>'disabled',
		       );


# text options
    my $textopt_f = $mw->Frame(-relief=>'groove',
			   -borderwidth=>2,
			   )->pack(-fill=>'both');
    my $verbose = 0;
    my $verb_label = $textopt_f->Label(-text=>"Verbose matching",
				   )->grid(-row=>0,
					   -column=>0,
					   -sticky=>'e');
    my $verb_lab_bal = $textopt_f->Balloon(-state=>'balloon',
					   -background=>'white');
    my $verb_help = "Displays word matches found in the annotation in the results box.";
    $verb_lab_bal->attach($verb_label,
			  -balloonmsg=>$verb_help);

    my $verb_c = $textopt_f->Checkbutton(-variable => \$verbose,
					 )->grid(-row=>0,
						 -column=>1,
						 -sticky=>'w');
    
    $textopt_f->Button(-text=>"Save Results",
		       -command=> [ \&saveresults,\$mw,\$logwin ],
		       -state=> 'normal',
		       )->grid(-row=>0,
			       -column=>2,
			       -sticky=>'e');    

    my $statusb = $mw->ROText(-height=>1,
			      -width=>60,
			      -wrap=>'word',
#			      -background=>'SystemButtonFace',
			      -relief=>'flat',
			      -border=>0,
			      )->pack(-side=>'left',
				      -anchor=>'sw');
#portability ok
    if ($^O =~ /mswin/i) {
	$statusb->configure(-background=>'SystemButtonFace');
    }
    else {
	$statusb->configure(-background=>'grey');
    }
    $statusb->insert('end','Idle');
    
    $mw->Button(-text=>"Run LACK",
		-command=> [ \&lackguimain,\$wordfile,\$datafile,\$annfile,\$iterations,\$mw,\$percent_done,\$rawout,\$logwin,\$stattype,\$verbose,\$statusb ],
		-state=> 'normal',
		)->pack(-pady=>4);

    $mw->Button(-text=>"Help",
		-command=> [\&makehelp,\$mw],
		)->pack(-pady=>4);
    
    $mw->Button(-text=>"Exit",
		-command=> sub { exit },
		)->pack(-pady=>2);
    MainLoop;
}

sub makehelp {
    my $mwref = shift;
    my $mw = $$mwref;

    my $helpwin = MainWindow->new(-title=>"LACK Help");
    $helpwin->focusForce;

    my $data = <<EOF;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=
EOF

    my $image = $helpwin->Photo(-data => $data);
    $helpwin->Icon( -image => $image );

    $helpwin->Button(-text=>"Close Help",
		     -command=> sub { $helpwin->destroy; },
		     )->pack(-pady=>10);

    my $hf = $helpwin->Frame()->pack(-fill=>'both',
				     -expand=>1,
				     );

    my $hn = $hf->NoteBook()->pack(-fill=>'both',
				   -expand=>1,
				   );
    my $overview = $hn->add("overview",
			 -label=>"Overview",
			 );

    my $files = $hn->add("files",
			 -label=>"File Formats",
			 );

    my $options = $hn->add("options",
			   -label=>"Commands and Options",
			   );

    my $stats = $hn->add("stats",
			 -label=>"Statistics",
			 );

    my $warn = $hn->add("warn",
			-label=>"Warnings",
			);

    my $add = $hn->add("add",
		       -label=>"Additional Help",
		       );

    my $ov_t = $overview->Scrolled('ROText',
				   -wrap=>'word',
				   -scrollbars=>'osoe',
				   )->pack(-fill=>'both',
					   -expand=>1,
					   );
    my $file_t = $files->Scrolled('ROText',
				  -wrap=>'word',
				  -scrollbars=>'osoe',
				  )->pack(-fill=>'both',
					  -expand=>1,
					  );
    my $opt_t = $options->Scrolled('ROText',
				   -wrap=>'word',
				   -scrollbars=>'osoe',
				   )->pack(-fill=>'both',
					   -expand=>1,
					   );
    my $stat_t = $stats->Scrolled('ROText',
				  -wrap=>'word',
				  -scrollbars=>'osoe',
				  )->pack(-fill=>'both',
					  -expand=>1,
					  );
    my $warn_t = $warn->Scrolled('ROText',
				 -scrollbars=>'osoe',
				 -wrap=>'word',
				 )->pack(-fill=>'both',
					 -expand=>1,
					 );
    my $add_t = $add->Scrolled('ROText',
			       -scrollbars=>'osoe',
			       -wrap=>'word',
			       )->pack(-fill=>'both',
				       -expand=>1,
				       );

    my $ov_data = <<EOF;
LACK is a tool for assessing lexical bias in analyzed microarray dataset.  The first step in a typical microarray analysis is to identify genes which are differentially regulated.  This is typically done using clustering software or statistical analysis software (such as SAM).

After the significant genes list (SGL) has been generated, it is often apparent that there are lexical trends in the SGL.  For example, genes of the same metabolic pathway are often co-regulated, and this results in certain words being over-represented in the SGL.  LACK is a tool for assessing the statistical significance of these apparent trends.
EOF

    my $file_data = <<EOF;
Three separate files are required to run LACK.


Wordlist File
=============
The word list file is a line-delimited text file of search terms.

  Example:
    redox
    oxidoreductase
    reductase
    glutathione
    thioredoxin     
    oxidase

Full Dataset File
=================
The full dataset file is the dataset used to generate the SGL.  The full dataset should be IDENTICAL to the dataset on which the analysis was performed.  This means that the full dataset used for LACK should already have had all data filtering performed prior to running LACK.  The only requirement is that each entry be on a separate line; tabs and other such delimiters are generally ignored.

Significant Genes File
======================
This is the file containing the SGL.  This file should be in the same format as the full dataset, only much smaller since it contains only genes which are differentially regulated.  Note that the SGL should be an exact subset of the full dataset.
EOF

    my $opt_data = <<EOF;
Statistics
==========
See the Statistics tab in the help.

Raw Counts Output
=================
If you wish to generate raw tally data for analysis using an external statistical method, perform a Poisson analysis and check Raw Counts Output.

Verbose matching
================
Selecting this option will report word matches in the full dataset.  This option can be useful for familiarizing oneself with how the pattern matching algorithm of LACK performs.

Save Results
============
Saves the text window results to a text file.

Run LACK
========
Executes LACK.  Note that all 3 files must be loaded prior to execution.

Help
====
Pop-up help window.

Exit
====
Exit LACK.

Status Window
=============
The lower left corner of the interface displays the current status of LACK.
EOF

    my $stat_data = <<EOF;
Two statistical methods are available for analysis of the SGL.

Binomial
========
The binomial approach is more accurate than Poisson, so it should be used whenever possible.  It may not be possible to use binomial statistics for some large datasets/large SGLs due to the large factorials required in calculation of the binomial coefficient.

Poisson
=======
In the cases which binomial modeling cannot be used, Poisson should be chosen for analysis.  Generally, 100 random samples (iterations) are enough to generate good p-values, but the time required to generate 1000 should be only incrementally longer;  we therefore recommend at least 1000 iterations.  Additionally, if Poisson statistics are used, p-values should be compared between at least two runs to ensure that one was not anomalous.

Additionally, Poisson can be used to generate raw tally data.  This data includes the number of genes in the random samples which contain a match for each iteration.  This data can then be analyzed by other statistical methods.  Additionally, researchers may want to consider saving this raw output anytime Poisson analysis is performed, since it is the only way to precisely reproduce the analysis.
EOF

    my $warn_data = <<EOF;
There are several pitfalls which can lead to a false determination of significance.  It is CRITICAL that these are avoided.

1)  The full dataset MUST be identical to the input into the SGL-generation method (e.g. Cluster).  The dataset must have already had all filters applied.  Using a genome annotation or whole microarray annotation is NOT appropriate, as the dataset used to generate the SGL may not be representative of a genome or even the microarray used.

2) Word selection must be performed with care to avoid bias.  For example, inconsistencies in annotation could cause some spots on a microarray to be annotated with the word "heme," with a single spot using the spelling "haeme."  If this single spot is generated in the SGL, is it appropriate to select it for the word list?  The bias has already been introduced, so in this case it may be more prudent to allow a fellow researcher to select heme-related words based on the full dataset without knowledge of the discrepancy in spellings.

3) Words should be selected from the full dataset, not the SGL.  If possible, the search terms should be chosen prior to generation of the SGL.  Many microarray experiments are exploratory and thus cannot achieve this; in this case, it becomes important to not generate bias by choosing words directly from the SGL.  If some genes of a pathway are differentially regulated in the SGL, then the wordlist should include ALL genes of the pathway (unless additional information is available regarding differential regulation of the genes in the pathway).  A rigorous way to achieve this would be to ask a colleague to select terms from the full dataset related to the hypothesis.
EOF

    my $add_data = <<EOF;
For additional help, see the LACK manual or contact the author at http://falkow.stanford.edu
EOF

    $ov_t->insert('end',$ov_data);
    $file_t->insert('end',$file_data);
    $opt_t->insert('end',$opt_data);
    $stat_t->insert('end',$stat_data);
    $warn_t->insert('end',$warn_data);
    $add_t->insert('end',$add_data);
}

sub saveresults {
    my $mwref = shift;
    my $mw = $$mwref;
    my $logwinref = shift;
# fix portability
    my $outfile = $mw->getSaveFile(-title=>'Save Results As');
    open(OUTFILE,">$outfile") or die "Can't open output file $outfile\n";
    print OUTFILE $$logwinref->get("1.0","end");
    close OUTFILE;
    $mw->messageBox(-title => 'Finished',
		    -message => 'Results Saved',
		    -type => 'OK');
}

sub modstate {
    my $iter_ref = shift;
    my $raw_ref = shift;
    my $stateref = shift;
    my $iter_l_ref = shift;
    my $raw_l_ref = shift;
    
# portability ok
    if ($^O =~ /mswin/i) {
	if ($$stateref == 0) {
	    $$iter_ref->configure(-state=>'disabled');
	    $$iter_ref->configure(-background=>'SystemButtonFace');
	    $$iter_ref->configure(-foreground=>'SystemDisabledText');
	    $$raw_ref->configure(-state=>'disabled');
	    $$iter_l_ref->configure(-foreground=>'SystemDisabledText');
	    $$raw_l_ref->configure(-foreground=>'SystemDisabledText');
	}
	elsif ($$stateref == 1) {
	    $$iter_ref->configure(-state=>'normal');
	    $$iter_ref->configure(-background=>'white');
	    $$iter_ref->configure(-foreground=>'SystemButtonText');
	    $$raw_ref->configure(-state=>'normal');
	    $$iter_l_ref->configure(-foreground=>'SystemButtonText');
	    $$raw_l_ref->configure(-foreground=>'SystemButtonText');
	}
	else {die "Problem with statistics state\n";}
    }
    else {
	if ($$stateref == 0) {
	    $$iter_ref->configure(-state=>'disabled');
	    $$iter_ref->configure(-background=>'lightgrey');
	    $$iter_ref->configure(-foreground=>'grey');
	    $$raw_ref->configure(-state=>'disabled');
	    $$iter_l_ref->configure(-foreground=>'grey');
	    $$raw_l_ref->configure(-foreground=>'grey');
	}
	elsif ($$stateref == 1) {
	    $$iter_ref->configure(-state=>'normal');
	    $$iter_ref->configure(-background=>'white');
	    $$iter_ref->configure(-foreground=>'black');
	    $$raw_ref->configure(-state=>'normal');
	    $$iter_l_ref->configure(-foreground=>'black');
	    $$raw_l_ref->configure(-foreground=>'black');
	}
	else {die "Problem with statistics state\n";}
    }
}


sub printlog {
    my $line = shift;
    my $logwinref = shift;
    my $logwin = $$logwinref;
    $logwin->configure(-state=>'normal');
    $logwin->insert('end',$line);
    $logwin->yview(moveto=>1);
#    $logwin->configure(-state=>'disabled');
    $logwin->update();
}

sub lackguimain {
    my $wordfileref = shift;
    my $wordfile = $$wordfileref;
    my $datafileref = shift;
    my $datafile = $$datafileref;
    my $annfileref = shift;
    my $annfile = $$annfileref;
    my $iterationsref = shift;
    my $iterations = $$iterationsref;
    my $mwref = shift;
    my $mw = $$mwref;
    my $progref = shift;
    my $rawoutref = shift;
    my $rawout = $$rawoutref;
    my $logwinref = shift;
    my $logwin = $$logwinref;
    my $stattyperef = shift;
    my $verboseref = shift;
    my $statusbref = shift;

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Clearing results');
    $mw->update;

    $logwin->configure(-state=>'normal');
    $logwin->delete('1.0','end');
    $logwin->configure(-state=>'disabled');
    $logwin->update();

    if ($$stattyperef == 0) {
	&lackguimain_binomial($wordfileref,$datafileref,$annfileref,$iterationsref,$mwref,$progref,$rawoutref,$logwinref,$verboseref,$statusbref);
    }
    elsif ($$stattyperef == 1) {
	&lackguimain_poisson($wordfileref,$datafileref,$annfileref,$iterationsref,$mwref,$progref,$rawoutref,$logwinref,$verboseref,$statusbref);
    }
    else {
	die "Statistics type not specified or not found\n";
    }
    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Idle');
    $mw->update;
    $$progref = 0;
}

sub lackguimain_binomial {
    my $wordfileref = shift;
    my $wordfile = $$wordfileref;
    my $datafileref = shift;
    my $datafile = $$datafileref;
    my $annfileref = shift;
    my $annfile = $$annfileref;
    my $iterationsref = shift;
    my $iterations = $$iterationsref;
    my $mwref = shift;
    my $mw = $$mwref;
    my $progref = shift;
    my $rawoutref = shift;
    my $rawout = $$rawoutref;
    my $logwinref = shift;
    my $logwin = $$logwinref;
    my $verboseref = shift;
    my $statusbref = shift;

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Beginning binomial analysis');
    $mw->update;

    if (!$wordfile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No word list file specified\n";
	return;
    }

    if (!$datafile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No dataset file specified\n";
	return;
    }

    if (!$annfile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No annotation file specified\n";
	return;
    }

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Reading search terms');
    $mw->update;

    my @wordlist;
    open(WORDLIST,$wordfile) or die "Couldn't open word file: $wordfile\n";
    while(<WORDLIST>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;
	push @wordlist, $_;
    }

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analyzing SGL');
    $mw->update;

    open(DATAFILE,$datafile) or die "Couldn't open analyzed dataset file: $datafile\n";
    my @dataann;
    my $datahits = 0;
    my $datasize = 0;
    while(<DATAFILE>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;

	my $temphit = &countwords(\@wordlist,$_);
	if ($temphit == 2) {
	    $datahits++;
#	    print "datahit: $_\n";
	}
	$datasize++;
    }
#    print "datahits: $datahits\t$datasize: $datasize\n";

# remember line numbers of hits in annotation
    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analyzing full dataset');
    $mw->update;

    open(ANNLIST,$annfile) or die "Couldn't open full dataset file: $annfile\n";

    my $prelimcount = 0;
    while(<ANNLIST>) {
	next if !$_;
	$prelimcount++;
    }

    seek ANNLIST,0,0;

    my $fulllinecount = 0;
    my %linehits;
    my $fullhits = 0;
    my $prog = $$progref;
    my $lastprog = 0;
    while(<ANNLIST>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;
	my $temphit = &countfullwords(\@wordlist,$_,$logwinref,$verboseref,$fulllinecount);
#	print "line: $fulllinecount\thit: $hits\n";
	if ($temphit == 2) {
#	    print "fullhit: $_\n";
	    $linehits{$fulllinecount} = 1;
	    $fullhits++;
	}
	$fulllinecount++;
	$prog = int(100 * $fulllinecount / $prelimcount);
#	print "$prog\n";
	if ($prog % 20 == 0) {
	    $$progref = $prog unless $lastprog == $prog;
	    $mw->update;
	}
	$lastprog = $prog;
    }
#    print "$fulllinecount\n";

    &printlog("\n",$logwinref) if $$verboseref;

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Calculating statistics');
    $mw->update;

    &printlog("Significant Dataset\n",$logwinref);
    &printlog("\tHits\t$datahits\n",$logwinref);
    &printlog("\tTotal Dataset\t$datasize\n",$logwinref);

    my @pval;
    my @histo;
    my $n = $datasize;
    my $X = 0;

    my $p = Math::BigFloat->new($fullhits);
    $p->bdiv($fulllinecount);

    my $q = Math::BigFloat->new('1');
    $q->bsub($p);

    my $cumulative = Math::BigFloat->new('0');
    my $massdensity = 0;
    my $curve_side_flag = 0;
    while () {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end',"Calculating binomial term for $X hits");
	$mw->update;

	my $n_over_n_minus_x = Math::BigInt->new('1');
	my $xfact = Math::BigInt->new('1');
	for (my $c = $n; $c > $n - $X; $c--) {
	    $n_over_n_minus_x->bmul($c);
	}
	for (my $d = 1; $d <= $X; $d++) {
	    $xfact->bmul($d);
	}

	my $nCxval = Math::BigFloat->new($n_over_n_minus_x);
	$nCxval->bdiv($xfact);

	my $term2 = Math::BigFloat->new($p);
	$term2->bpow($X);
	my $term3 = Math::BigFloat->new($q);
	$term3->bpow($n-$X);

	my $temp_p = Math::BigFloat->new($nCxval);
	$temp_p->bmul($term2);
	$temp_p->bmul($term3);

	my $temp_histo = $temp_p * 100; # 100 is arbitrary
	my $temp_p2 = sprintf("%.10f",$temp_p);

	$temp_p2 = '<0.0000000001' if $temp_p2 == 0;

	$massdensity = $temp_p2 if $X == $datahits;
	$cumulative += $temp_p if $X <= $datahits;
	$temp_histo = &myround($temp_histo);
	push @pval, $temp_p2;
	push @histo, $temp_histo;
	if ($temp_p > 0.01 && $curve_side_flag == 0) {
	    $curve_side_flag++;
	}
	last if $temp_p < 0.00001 && $curve_side_flag && $X >= $datahits; # arbitrary cutoff
	$X++;
    }

    $cumulative->ffround(-10);
    my $invcumul = 1 - $cumulative;
    $cumulative = $cumulative->bstr;

    if ($cumulative == 1) {
	$cumulative = '>0.9999999999';
    }
    if ($massdensity == 0) {
	$massdensity = '<0.0000000001';
    }
    if ($invcumul == 0) {
	$invcumul = '<0.0000000001';
    }

    &printlog("\tp(x <= $datahits)\t$cumulative\n",$logwinref);
    &printlog("\tp(x = $datahits)\t$massdensity\n",$logwinref);
    &printlog("\tp(x > $datahits)\t$invcumul\n",$logwinref);

# OUTPUT STATS
    &printlog("\nCalculated Binomial Distribution\n",$logwinref);
    &printlog("\n\tDistribution Statistics\n",$logwinref);
    my $mean = $n*$p;
    $mean = sprintf("%.10f",$mean);
    &printlog("\t\tMean\t$mean\n",$logwinref);

# HISTOGRAM BIN & FREQ OUTPUT
    &printlog("\n\tHistogram Tally\n",$logwinref);
    &printlog("\t\tHits\tExpected frequency in 100 samples\tp(x = Hits)\n",$logwinref);
    for (my $c = 0; $c<= $#histo; $c++) {
	&printlog("\t\t$c\t$histo[$c]\t$pval[$c]\n",$logwinref);
    }

#    close OUTFILE;
    $$progref = 100;
    $mw->update;
    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analysis complete');
    $mw->update;

    $mw->messageBox(-title => 'Program Finished',
		    -message => 'Processing complete',
		    -type => 'OK');
}

sub myround {
    my $num = shift;
    my $intnum = int($num);
    my $remain = $num - $intnum;

    return $intnum if $remain < 0.5;
    return $intnum+1;
}

sub lackguimain_poisson {
    my $wordfileref = shift;
    my $wordfile = $$wordfileref;
    my $datafileref = shift;
    my $datafile = $$datafileref;
    my $annfileref = shift;
    my $annfile = $$annfileref;
    my $iterationsref = shift;
    my $iterations = $$iterationsref;
    my $mwref = shift;
    my $mw = $$mwref;
    my $progref = shift;
    my $rawoutref = shift;
    my $rawout = $$rawoutref;
    my $logwinref = shift;
    my $logwin = $$logwinref;
    my $verboseref = shift;
    my $statusbref = shift;

    my $poissonconfirm = $mw->messageBox(-title => 'Confirm Poisson',
					  -message => 'This version of LACK contains an update that allows processing of very large factorials, allowing use of binomial statistics even for very large datasets.  However, Poisson statistics, while slightly less accurate, can be computed faster.  Are you sure you wish to use Poisson statistics?',
					  -type => 'YesNo',
					  -default => 'yes');
    

#    print "$poissonconfirm\n";
    if ($poissonconfirm =~ /no/i) {
	return;
    }

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Beginning Poisson analysis');
    $mw->update;

    if (!$wordfile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No word list file specified\n";
	return;
    }

    if (!$datafile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No dataset file specified\n";
	return;
    }

    if (!$annfile) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "No annotation file specified\n";
	return;
    }

    if (!$iterations) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "Must specify non-zero number of iterations\n";
	return;
    }

    if ($iterations =~ /\D/) {
	$$statusbref->delete('1.0','end');
	$$statusbref->insert('end','Error');
	die "Iterations must be numeric\n";
	return;
    }



    if ($iterations < 100) {
	my $answer = $mw->messageBox(-title => 'Warning',
				     -type => 'YesNo',
				     -default => 'no',
				     -message => "This program uses a statistical parameter which assumes many iterations.  You have chosen to use only $iterations iterations, which could cause inaccurate statistical results.  Do you wish to proceed?");
	unless ($answer eq 'yes') {
	    	$$statusbref->delete('1.0','end');
		$$statusbref->insert('end','Error');
		return;
	    }
    }

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Reading search terms');
    $mw->update;

    my @wordlist;
    open(WORDLIST,$wordfile) or die "Couldn't open word file: $wordfile\n";
    while(<WORDLIST>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;
	push @wordlist, $_;
    }

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analyzing SGL');
    $mw->update;

    open(DATAFILE,$datafile) or die "Couldn't open analyzed dataset file: $datafile\n";
    my @dataann;
    my $datahits = 0;
    my $datasize = 0;
    while(<DATAFILE>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;

	my $temphit = &countwords(\@wordlist,$_);
	if ($temphit == 2) {
	    $datahits++;
#	    print "datahit: $_\n";
	}
	$datasize++;
    }
#    print "datahits: $datahits\t$datasize: $datasize\n";

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analyzing full dataset');
    $mw->update;

    $$progref = 1;

# remember line numbers of hits in annotation
    open(ANNLIST,$annfile) or die "Couldn't open full dataset file: $annfile\n";
    my $prelimcount = 0;
    while(<ANNLIST>) {
	next if !$_;
	$prelimcount++;
    }

    seek ANNLIST,0,0;

    my $fulllinecount = 0;
    my %linehits;
    my $prog = $$progref;
    my $lastprog = 0;
    while(<ANNLIST>) {
	chomp;
	$_ =~ s/\r//;
	next if !$_;
	my $temphit = &countfullwords(\@wordlist,$_,$logwinref,$verboseref,$fulllinecount);
#	print "line: $fulllinecount\thit: $hits\n";
	if ($temphit == 2) {
#	    print "fullhit: $_\n";
	    $linehits{$fulllinecount} = 1;
	}
	$prog = int(100 * $fulllinecount / $prelimcount);
#	print "$prog\n";
	if ($prog % 20 == 0) {
	    $$progref = $prog unless $prog == $lastprog;
	    $mw->update;
	}
	$lastprog = $prog;
	$fulllinecount++;
    }
#    print "$fulllinecount\n";

    &printlog("\n",$logwinref) if $$verboseref;

#    $$progref = 1;
#    $mw->update;

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Generating random samples');
    $mw->update;

#    my $outfile = $mw->getSaveFile(-title=>'Save Results As');
#    open(OUTFILE,">$outfile") or die "Can't open output file $outfile\n";
    &printlog("Significant Dataset\n",$logwinref);
    &printlog("\tHits\t$datahits\n",$logwinref);
    &printlog("\tTotal Dataset\t$datasize\n",$logwinref);

    my @statdata;
    for (my $d = 0; $d < $iterations; $d++) {
	my @int = &randint($fulllinecount,$datasize);

	my $fullhits = 0;
	foreach (@int) {
	    if ($linehits{$_}) {
		$fullhits++;
	    }
	}
#	print "fullhits: $fullhits\n";
	push @statdata, $fullhits;
    }

# GENERATE STATS

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Calculating statistics');
    $mw->update;

    my @stats = &calcdescstat(\@statdata);

    my $mean = $stats[1];
#    my $stdev = $stats[2];

    my $p_less_than_hits;
    for (my $c = 0; $c < $datahits; $c++) {
	my $tempval = ($mean ** $c) * exp(-$mean) / factorial($c);
	$p_less_than_hits += $tempval;
    }

    my $p_hits = ($mean ** $datahits) * exp(-$mean) / factorial($datahits);

    my $ptotal = $p_less_than_hits + $p_hits;
    &printlog("\tp(x <= $datahits)\t$ptotal\n",$logwinref);
    &printlog("\tp(x = $datahits)\t$p_hits\n",$logwinref);

# OUTPUT STATS
    &printlog("\nPoisson Random Sampling\n",$logwinref);
    &printlog("\n\tDistribution Statistics\n",$logwinref);
    &printlog("\t\tCount\t$stats[0]\n",$logwinref);
    &printlog("\t\tMean\t$stats[1]\n",$logwinref);
    &printlog("\t\tMin\t$stats[3]\n",$logwinref);
    &printlog("\t\tMax\t$stats[4]\n",$logwinref);

# HISTOGRAM BIN & FREQ OUTPUT
    my %histotally = ();
    foreach (@statdata) {
	$histotally{$_}++;
    }
    my $min = $stats[3];
    my $max = $stats[4];

    &printlog("\n\tHistogram Tally\n",$logwinref);
    &printlog("\t\tHits\tFrequency\n",$logwinref);
    for (my $c = $min; $c <= $max; $c++) {
	if ($histotally{$c}) {
	    &printlog("\t\t$c\t$histotally{$c}\n",$logwinref);
	}
	else { &printlog("\t\t$c\t0\n",$logwinref); }
    }

# RAW COUNTS OUTPUT
    if ($rawout) {
	my $rawout = $mw->getSaveFile(-title=>'Save Raw Poisson Results As');
	open(RAWOUT,">$rawout") or die "Can't open output file $outfile\n";
	print RAWOUT "Raw Poisson Sample Counts\n";
	print RAWOUT "\tHits\tTotal Dataset Size\n";
	foreach (@statdata) {
	    print RAWOUT "\t$_\t$datasize\n";
	}
	close RAWOUT;
    }

    $$progref = 100;
    $mw->update;

    $$statusbref->delete('1.0','end');
    $$statusbref->insert('end','Analysis complete');
    $mw->update;

    $mw->messageBox(-title => 'Program Finished',
		    -message => 'Processing complete',
		    -type => 'OK');
}

sub lackcommand {
    my ($wordfile,$datafile,$annfile,$iterations,$rawout,$outfile) = @_;

    if (!$wordfile) {
	die "No word list file specified\n";
	return;
    }

    if (!$datafile) {
	die "No dataset file specified\n";
	return;
    }

    if (!$annfile) {
	die "No annotation file specified\n";
	return;
    }

    if (!$iterations) {
	die "Must specify non-zero number of iterations\n";
	return;
    }

    if ($iterations =~ /\D/) {
	die "Iterations must be numeric\n";
	return;
    }

    if (!$outfile) {
	die "No output file specified\n";
	return;
    }

    print "Reading wordlist ...";
    my @wordlist;
    open(WORDLIST,$wordfile) or die "Couldn't open word file: $wordfile\n";
    while(<WORDLIST>) {
	chomp;
	push @wordlist, $_;
    }
    print " complete\n";

    print "Tallying terms in analyzed data file ...";
    open(DATAFILE,$datafile) or die "Couldn't open analyzed dataset file: $datafile\n";
    my @dataann;
    my $datahits = 0;
    my $datasize = 0;
    while(<DATAFILE>) {
	chomp;
	next if !$_;

	my $temphit = &countwords(\@wordlist,$_);
	if ($temphit == 2) {
	    $datahits++;
#	    print "datahit: $_\n";
	}
	$datasize++;
    }
#    print "datahits: $datahits\t$datasize: $datasize\n";
    print " complete\n";

    print "Tallying terms in full data file ...";
# remember line numbers of hits in annotation
    open(ANNLIST,$annfile) or die "Couldn't open full dataset file: $annfile\n";
    my $fulllinecount = 0;
    my %linehits;
    while(<ANNLIST>) {
	chomp;
	next if !$_;
	my $temphit = &countwords(\@wordlist,$_);
#	print "line: $fulllinecount\thit: $hits\n";
	if ($temphit == 2) {
#	    print "fullhit: $_\n";
	    $linehits{$fulllinecount} = 1;
	}
	$fulllinecount++;
    }
#    print "$fulllinecount\n";
    print " complete\n";

    open(OUTFILE,">$outfile") or die "Can't open output file: $outfile\n";
    print OUTFILE "Significant Dataset\n";
    print OUTFILE "\tHits\t$datahits\n";
    print OUTFILE "\tTotal Dataset\t$datasize\n";

    my @statdata;
    $| = 1;
    for (my $d = 0; $d < $iterations; $d++) {
	print "\b" x 60, "Generating and tallying random datasets ...";
	print " iteration ", $d+1;
	my @int = &randint($fulllinecount,$datasize);

	my $fullhits = 0;
	foreach (@int) {
	    if ($linehits{$_}) {
		$fullhits++;
	    }
	}
#	print "fullhits: $fullhits\n";
	push @statdata, $fullhits;
    }
    print " complete\n";

    print "Generating stats and output file ...";
# GENERATE STATS
    my @stats = &calcdescstat(\@statdata);

    my $mean = $stats[1];
#    my $stdev = $stats[2];

    my $p_less_than_hits;
    for (my $c = 0; $c < $datahits; $c++) {
	my $tempval = ($mean ** $c) * exp(-$mean) / factorial($c);
	$p_less_than_hits += $tempval;
    }

    my $p_hits = ($mean ** $datahits) * exp(-$mean) / factorial($datahits);

    print OUTFILE "\tp(x <= $datahits)\t", $p_less_than_hits + $p_hits, "\n";
    print OUTFILE "\tp(x = $datahits)\t$p_hits\n";

# OUTPUT STATS
    print OUTFILE "\nRandomized Annotation Set\n";
    print OUTFILE "\n\tDistribution Statistics\n";
    print OUTFILE "\t\tCount\t$stats[0]\n";
    print OUTFILE "\t\tMean\t$stats[1]\n";
    print OUTFILE "\t\tMin\t$stats[3]\n";
    print OUTFILE "\t\tMax\t$stats[4]\n";

# HISTOGRAM BIN & FREQ OUTPUT
    my %histotally = ();
    foreach (@statdata) {
	$histotally{$_}++;
    }
    my $min = $stats[3];
    my $max = $stats[4];

    print OUTFILE "\n\tHistogram Tally\n";
    print OUTFILE "\t\tHits\tFrequency\n";
    for (my $c = $min; $c <= $max; $c++) {
	if ($histotally{$c}) {
	    print OUTFILE "\t\t$c\t$histotally{$c}\n";
	}
	else { print OUTFILE "\t\t$c\t0\n"; }
    }

# RAW COUNTS OUTPUT
    if ($rawout) {
	print OUTFILE "\n\tRaw Counts\n";
	print OUTFILE "\t\tHits\tTotal Dataset Size\n";
	foreach (@statdata) {
	    print OUTFILE "\t\t$_\t$datasize\n";
	}
    }

    close OUTFILE;
    print " complete\n";
}

sub randint {
    my @integers = ();
    my %intcheck;
    my $c = 0;
    while ($c <= $_[1]) {
	my $randint = int(rand($_[0]));
	next if $intcheck{$randint};
	$intcheck{$randint} = 1;
	push @integers, $randint;
	$c++;
    }
    return @integers;
}

sub countwords {
    my $wordlistref = shift;
    my @wordlist = @{$wordlistref};
    my $annotation = shift;
    my $hitcounter = 0;

    my $hit = 1;
    foreach my $word (@wordlist) {
	if ($annotation =~ /($word)/i) {
	    next unless ($annotation =~ /\b$word/ || $annotation =~ /$word\b/);
#	    print "$word\t$annotation\n";
	    $hit++;
	    last;
	}
    }
    return $hit; # 1 = no match, 2 = match
}

sub countfullwords {
    my $wordlistref = shift;
    my @wordlist = @{$wordlistref};
    my $annotation = shift;
    my $hitcounter = 0;
    my $logwinref = shift;
    my $verboseref = shift;
    my $linecount = shift;

    my $hit = 1;
    foreach my $word (@wordlist) {
	if ($annotation =~ /($word)/i) {
	    next unless ($annotation =~ /\b($word)/ || $annotation =~ /($word)\b/);
#	    print "$word\t$annotation\n";
	    my $hitreport = "Found term ($1) in line $linecount $annotation\n";
	    &printlog($hitreport,$logwinref) if $$verboseref;
	    $hit++;
	    last;
	}
    }
    return $hit; # 1 = no match, 2 = match
}

sub factorial {
    my $n = shift;
    return undef if $n < 0; 
    return 1 if $n == 0; 
    return $n * factorial($n - 1);
} 

sub calcdescstat {
    my $dataref = shift;
    my @data = @{$dataref};

    my $stat = Statistics::Descriptive::Full->new();
    $stat->add_data(@data);
    my $count = $stat->count();
    my $mean = $stat->mean();
    my $stdev = $stat->standard_deviation();
    my $min = $stat->min();
    my $max = $stat->max();
    my $p1 = $stat->percentile(1);
    my $p5 = $stat->percentile(5);
    my $p95 = $stat->percentile(95);
    my $p99 = $stat->percentile(99);

    return ($count,$mean,$stdev,$min,$max,$p1,$p5,$p95,$p99);
}
    
sub selectsinglefile {
    my $entryblankref = shift;
    my $entryblank = $$entryblankref;
    my $mwref = shift;
    my $mw = $$mwref;

    my $file;
    if ($^O =~ /mswin/i) {
	my $opentypes = [
			 "{All files}     *           ",
			 "{PCL files}     {.pcl}      ",
			 "{Text files}    {.txt}      ",
			 ];
	$file = $mw->getOpenFile(-filetypes=>$opentypes);
    }
    else {
	$file = $mw->getOpenFile(-title=>'Load File');
    }
    if (defined $file and $file ne '') {
	$entryblank->delete(0, 'end');
	$entryblank->insert(0, $file);
	$entryblank->xview('end');
    }
}