#!/usr/bin/perl
# Copyright (C) 2007-2011 Ian Korf, Genís Parra, and Keith Brandam
#
# 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.

use strict; use warnings;
use FAlite;
use Getopt::Std;
use vars qw($opt_w $opt_s $opt_r $opt_g $opt_d $opt_a $opt_c $opt_f $opt_o);

################################
#
#   S e t u p
#
################################

# set up some default values
my $window_step = 1;
my $window_size = 7;
my $donor = 5;
my $acceptor = 10;
my $cutoff      =  1.2;
my $gap         = 5; # how far can two peaks be apart to still be considered one peak?
my $gff         = 0; 
my $weighting_factor = 200;

getopts('w:s:d:c:a:f:g:ro');
$window_size   = $opt_w if $opt_w;
$window_step  = $opt_s if $opt_s;
$donor = $opt_d if $opt_d;
$acceptor = $opt_a if $opt_a;
$cutoff = $opt_c if $opt_c;
$gap = $opt_g if $opt_g;
$weighting_factor = $opt_f if $opt_f;

$gff = 1 if $opt_o;

die "
usage: imeter_window.pl [options] <fasta file>

options:
  -w <int>     window size nt    [default $window_size]
  -s <int>     step size  nt     [default $window_step]
  -d <int>     donor sequence to clip [default $donor]
  -a <int>     acceptor sequence to clip [default $acceptor]
  -g <int>     minimum gap allowed between high scoring windows [default $gap]
  -c <float>   threshold value to decide what is a high scoring window [default $cutoff]
  -f <int>     weighting factor to penalize peaks that are further away [default $weighting_factor]

  -r           calculate score for reverse strand
  -o		   print GFF info of each peak

" unless @ARGV == 1;

die "Window size (-w) must be at least 5\n" if ($window_size < 5);
die "Window step (-s) must be <= window size (-w)\n" if ($window_step > $window_size);

my ($FASTA) = @ARGV;


######################################
#
#   R e a d   P a r a m e t e r s
#
######################################

my %pentamer_scores;

while (<DATA>) {
	my ($word, $score) = split;
	$pentamer_scores{$word} = $score;
}


################################
#
#   M a i n   L o o p
#
################################

# check for standard input otherwise open regular filehandle
my ($fasta, $input);

if ($FASTA eq '-') {
	$fasta = new FAlite(\*STDIN);
} else {
    open($input,"<", $FASTA) or die "Can't open $FASTA\n";
    $fasta = new FAlite(\*$input);
}

while (my $entry = $fasta->nextEntry) {
	my ($id) = $entry->def =~ /^>(\S+)/;
	my $seq = uc $entry->seq;
	

	# clip sequence to remove donor and acceptor?
	$seq = substr($seq, $donor, -$acceptor);
	
	# loop over input sequence in pentamer windows, and extract score from %pentamer_scores
	my @records;
	for (my $i = 0; $i <= length($seq) - 5; $i++){
	    my $subseq = substr($seq, $i, 5);
		# are we working on reverse strand?
		$subseq = reverse_complement(substr($seq, $i, 5)) if ($opt_r);
		$records[$i]{start}  = $i;
	   	$records[$i]{end}    = $i + 4;
	   	$records[$i]{score}  = $pentamer_scores{$subseq};
#		print "$records[$i]{start}-$records[$i]{end}) $records[$i]{score}\n";
	}					

	# now we want to make a list of the windows whose average score (per base) exceeds the $cutoff value
	# this loop starts at the middle position of the first window (e.g. position 3)
	# and loops through the middle position of the last window
	# but will calculate the window score from 1st base to end of window (e.g. 1 to 5)
	my @windows = ();
	my $high_scoring_window_count = 0;
	
	for (my $i = 0; $i < @records - $window_size + 5; $i += $window_step){

		my ($start, $end) = ($i, $i + $window_size - 1); 
		my $window_score = 0;
		
		# now loop through all pentamers that comprise the window and add their score to $window_score
	  	for (my $j = $start; $j + 4 <= $end; $j++){
		 	$window_score +=  $records[$j]{score};
		}

		# if window score is above cutoff, store details...but store average score per base
 		if ($window_score >= $cutoff) {
       		my $avg_score = $window_score/$window_size;
    		$windows[$high_scoring_window_count]{start}     = $i;
    		$windows[$high_scoring_window_count]{end}       = $i + $window_size - 1;
    		$windows[$high_scoring_window_count]{avg_score} = $avg_score;
    		$high_scoring_window_count++;		    
#			print "$start-$end\tHigh scoring window \#$high_scoring_window_count\tavg_score per base = $avg_score\n";
 		} else {
#			print "$start-$end\n";
		}
	}
		
	################################
	#
	#   F i n d   P e a k s 
	#
	################################

   	my @peak; 
   	my $peak_counter = 0;

    # Genis automatically defines first peak as equal to the first high scoring window. Why?
   	$peak[0]{start}     = $windows[0]{start};
   	$peak[0]{end}       = $windows[0]{end};
   	$peak[0]{avg_score} = $windows[0]{avg_score};

	# loop through remaining high scoring windows  I.e. start at $i = 1 rather than 0
   	for (my $i = 1; $i < @windows; $i++ ){
	#	print "$i) $windows[$i]{start}-$windows[$i]{end}) avg_score = $windows[$i]{avg_score}\n";

		# now ask whether current window is within $gap nt of current peak
    	if ($windows[$i]{start} - $peak[$peak_counter]{end} < $gap){
#			print "\tBEFORE: Peak $peak_counter\t$peak[$peak_counter]{start}-$peak[$peak_counter]{end} $peak[$peak_counter]{avg_score}\n";

			# if window overlaps peak, then change end coordinate of current peak...
        	$peak[$peak_counter]{end} = $windows[$i]{end};

			# also change the score of the peak by making a new average score
    	 	$peak[$peak_counter]{avg_score} = (($peak[$peak_counter]{avg_score} + $windows[$i]{avg_score}) / 2);

#			print "\tAFTER:  Peak $peak_counter\t$peak[$peak_counter]{start}-$peak[$peak_counter]{end} avg_score = $peak[$peak_counter]{avg_score}\n\n";
      	} else {
			# at this point you have defined one peak and can start looking for the next one
			# increment peak counter and set default values of 2nd peak to be that of current window (???)
        	$peak_counter++;
	 		$peak[$peak_counter]{start}     = $windows[$i]{start};
	 		$peak[$peak_counter]{end}       = $windows[$i]{end};
	 		$peak[$peak_counter]{avg_score} = $windows[$i]{avg_score};
      	}
	}

	################################
	#
	#   S c o r e   P e a k s 
	#
	################################
	
	my $imeter2_score = 0;

    for (my $i = 0; $i <= $peak_counter; $i++ ){  		
    	my $peak_score = 0;
		
		# just skip forward if there are no peaks
		next if not defined($peak[$i]{start});
#		print "$i) $peak[$i]{start}-$peak[$i]{end}\n";

	 	for (my $j = $peak[$i]{start}; $j <= $peak[$i]{end} - 4; $j++){
			$peak_score +=  $records[$j]{score};
       	}

		# calculate a weighted score based on distance of peak
		# should have two variables here? distance based on start or middle of peak?
		# 1/200 could also be variable
		# include a donor offset in case a large amount of sequence was clipped
        my $weighted_score = $peak_score * exp(-($peak[$i]{start}+$donor) * 1/$weighting_factor); 
#		print "$i) $peak[$i]{start}-$peak[$i]{end}\tavg_score per base = $peak[$i]{avg_score}\tTotal peak score = $peak_score\tweighted score = $weighted_score\n";
	    printf("%s\tIMEter\tpeak\t%d\t%d\t%.2f\t+\t.\t.\n", $id, $peak[$i]{start}, $peak[$i]{end}, $weighted_score) if ($gff);	     
	    $imeter2_score += $weighted_score;
	}
	
	# with large window sizes can end up in situations where individually positive scoring
	# windows can be connected by short regions of negative score. Can end up producing a single
	# large negative peak. So should always set to zero if this happens.
	$imeter2_score = 0 if ($imeter2_score < 0);
	# print out final score
	my $formatted_score = sprintf("%.2f",$imeter2_score);
	print "$id\t$formatted_score\n" if (!$gff);
}

close $input if ($FASTA ne '-');

exit(0);

############################ 
#
#   S U B R O U T I N E S 
#
#############################


sub reverse_complement {
        my ($seq) = @_;
        $seq = reverse $seq;
        $seq =~ tr[ACGTRYMKWSBDHVacgtrymkwsdbhv]
                  [TGCAYRKMSWVHDBtgcayrkmswvhdb];
        return $seq;
}

exit(0); 

__DATA__
CGCCG	1.9580717108796
CGGCG	1.89858928684913
CGATT	1.68863052531273
CGCGA	1.53667722117749
CGATC	1.53403084338351
CGTCG	1.46858951901267
TCGAT	1.46420405405747
CGACG	1.44336022300819
TCGCG	1.44145179886508
GGGTT	1.35746397134248
TTCGA	1.33065188608934
TCCGA	1.31535436911392
TAGGG	1.30875596065583
GATCG	1.29712261029596
CCGAT	1.23538159551726
AGGGT	1.22400503605628
CGAAT	1.21952606581964
CGCGT	1.16873483963394
CTGGG	1.16846062383037
AATCG	1.16092466449249
TCGAA	1.10557017686345
ATTCG	1.09071473475617
ATCGA	1.08390957678889
GCGAT	1.07898018687561
CTCCG	1.05658125879546
CTTCG	1.04815333484276
ATCGG	1.03260130108353
CTCGA	1.028601858824
TCGGA	1.00050734586122
TCTCG	0.971621826745853
TTCGT	0.952693930736816
CCGCG	0.947333620700545
TGGGT	0.932790145711152
GTTCG	0.925407959931484
TTTCG	0.923184630271459
GCGCG	0.904950787100565
CGCGC	0.896010742747351
GATTT	0.884967290549799
CGGAT	0.839427214380983
TTAGG	0.833409505673864
TTCGC	0.829408458555992
ACGCG	0.823414896392352
TCGTC	0.816841155397732
GATTC	0.813734269542041
GGCGA	0.810974638891551
GCGAA	0.801083708944288
TCGTT	0.794851840541371
GATCT	0.79228837704842
TCGAG	0.77551545056079
CGGAG	0.772681475947738
GAATT	0.768895625240019
GCTCG	0.765717528197974
TCGTG	0.765536197778033
ATCGC	0.753830731787942
TTCCG	0.753777067085019
AGATC	0.743416759544082
GGATT	0.738459869539721
GTCGG	0.732836783296118
CGAGA	0.720740440485157
TCGCT	0.718581034584657
GGGGG	0.70448620469887
ACGAT	0.70069365311742
TCGGC	0.679770548392498
ATCCG	0.67158552743916
GAATC	0.668362418258892
CGATG	0.668253666741412
ATCGT	0.663349985957075
GGATC	0.653414789993102
TGATT	0.651859535050857
GATTG	0.651371333188124
GTCGA	0.640126339788273
TACGA	0.638587759938491
TGCGA	0.635404435732243
CGTTG	0.620786927905642
CTCTC	0.612646291653529
TTGGG	0.611663191383443
AGCGA	0.609359977687843
GGTTT	0.60678020402394
TCGCC	0.600166777163455
CGGAA	0.599570252432654
TCTGG	0.575313160853235
TTGAT	0.57405149184092
AATTG	0.56428349148006
GACGA	0.556870881776073
TTTGA	0.548013098283707
CATCG	0.539451689142155
CTCGC	0.538257679660418
AATTT	0.537571354653054
AGATT	0.533597316279989
CGAAA	0.533279116412035
TCCGT	0.530125273679323
TGGGG	0.528076971661135
CGTGA	0.521442707482325
GATCC	0.520384510537196
GGGGT	0.518610594926785
CGTTT	0.517700993843756
CAATT	0.512335633746589
CTCGT	0.503807665299624
TCTCT	0.502758812047804
GCCGA	0.500884405642724
TCCGG	0.490277650758596
CTAGG	0.489607837019728
CCGCC	0.488352773834104
TCGTA	0.487567615078276
CGAGT	0.487284506446613
ATTGA	0.47611957533133
TTGCG	0.474565323488285
TCTTC	0.471488172619884
CGAAG	0.471402704904167
TGGAT	0.465313844186266
GGAAT	0.465230248365438
CCGAC	0.464033094638691
GAGAT	0.455860053701235
AATTC	0.455406775124901
CGTGT	0.454670371731613
ATCTG	0.452193583001034
TAGGT	0.449154206206427
TGTCG	0.448125416452959
ACGAA	0.440473712196741
CCGGA	0.439382429577612
CGTCT	0.437924187673594
GCGTT	0.436974343823236
CGGTG	0.430347170398538
GGGTC	0.425926824253123
TCGCA	0.425689888312575
TTTAG	0.425293677388668
GCGAG	0.421765016102562
GTTGA	0.420638571947255
GATTA	0.41775407143528
TTGAG	0.414369128014788
ATTTG	0.413158501792671
TTTTG	0.403318742169936
TATCG	0.400953982619998
TAGAT	0.400516415097981
TTACG	0.391756796723354
AAATT	0.389639056870056
TGAAT	0.386753486554355
TTCTC	0.380445833910427
CCGGC	0.379489298128071
ATTAG	0.378677957438089
TCAAT	0.377132106537503
CTCTG	0.37709182435122
ATTGG	0.375823413399552
TGATC	0.375193304905936
TTGGA	0.369752324992483
ACGGA	0.369295320906443
GGGAT	0.365367420678465
GACGG	0.359381724679496
TTTGG	0.356224770403762
TCACG	0.353325980376382
CGCTT	0.353028548143417
CACGA	0.352287271674337
TGCGT	0.351674627796777
GTTTC	0.351013202018079
CGTAG	0.349831696639845
CGCGG	0.34396286449893
TTGAA	0.342787770792165
AGGTT	0.341919255188085
GAAAT	0.341655671021215
GGGGA	0.339804383017196
CTGGA	0.335536987628781
CAGAT	0.329676913524751
ATTTC	0.327881399863137
GCGGA	0.327765636971128
GTGTT	0.325619681351018
TTTTT	0.320951827266984
AACGA	0.319371976534809
GTTTT	0.31816186232913
TTAGA	0.316456895662144
CGTTC	0.313556450216839
GTCGT	0.309525909849445
TCGAC	0.308698273160184
CGAGG	0.307305840340378
GTTTG	0.307300685105561
TTCGG	0.304505396159422
TCTCC	0.303393354781151
GGTTG	0.301577309497946
GAGCT	0.299993053517199
GGTCG	0.299763060588394
GTGGG	0.298397747036893
ACGAG	0.293236965909734
TCTGA	0.289173286924383
GCCGC	0.285859909935361
AATCT	0.285726199407039
ATTTT	0.285709175242844
ATCTC	0.281640124849346
AGCTC	0.281167507199299
CGTAA	0.276016433637018
CGGCC	0.272765530402771
GTACG	0.271830940622156
TCTGT	0.269055158920522
TCCCG	0.267823096514846
TACGG	0.265960352497656
TTTGT	0.265782951526918
TGTTG	0.263923954693901
CTGCG	0.261682715162143
CCTCG	0.260590816456668
TCGGG	0.260062588916757
TGAGA	0.260047132789181
GGAGA	0.257828947693203
GTCGC	0.257391073772486
CGCTC	0.257330047354216
TTGTG	0.257051047670598
TAATT	0.256860674873277
TTGTT	0.256476688297139
GTGAT	0.256013399993321
CGGGA	0.249991237080519
CTTCT	0.249741497412638
ACGCC	0.249321410383867
GATGA	0.247063321083149
TGTGT	0.246695940977044
CGAAC	0.245670202940741
CCCTA	0.245615782233538
TGGGA	0.243619184743254
GGGAA	0.243204438429951
CCCCG	0.242876739384615
ATGGG	0.242486698817857
CCCGC	0.237391200300885
AACCC	0.234574535913631
GTTGT	0.232554587478665
CGTTA	0.232362361442737
GAGTT	0.231563123534815
GCCGG	0.23021716741315
GAGCG	0.228929621552689
CGAGC	0.222168377576661
TGTTC	0.221044181947151
GAGAA	0.219555264301105
TCGGT	0.219518834551903
GAGAG	0.208380831657565
CGCCC	0.206459340748994
AAATC	0.202859754946927
GGTGA	0.201215619117446
GGTTC	0.20119441228521
GTTTA	0.197274799154291
TTCAA	0.196414917939348
GTGAG	0.195691909020497
TGAGT	0.195405159459963
GTAAT	0.192303996850478
TGGAG	0.19040931949048
GCGTA	0.189198942193659
TAGCG	0.18636154794557
CGTAT	0.185853613303813
GGCGT	0.185302689152431
CGCCA	0.184473315722928
CTCGG	0.184193634614107
GTGTG	0.183498192305683
TCAGA	0.18323943613229
TGGCG	0.182894048644891
TGTTT	0.182863893584129
TTCTG	0.182503573141235
GTGAA	0.182355915887428
GCTTC	0.181551563518676
CGGGG	0.180924248641857
AGGAT	0.180227074287396
AGTTT	0.17541070959167
AGCTT	0.174294364975844
TGTGA	0.171158732676561
GAAGA	0.170248578242138
GTGGA	0.169784645058391
CCGTC	0.168578101620764
GATCA	0.167382101568694
CTGAT	0.167322584595177
TCCTC	0.166732486722795
GTGCG	0.165984228617908
TTGGT	0.163434885624097
TGGAA	0.16270220029749
AATTA	0.16207553170491
TCTAG	0.157143946846453
CAACG	0.154929040108913
CCGAA	0.154929040108913
ATTGT	0.154693786126999
TAGCT	0.153151852856246
GGGCT	0.153036980767704
GTTCT	0.152082551107451
GTAGA	0.149061010353521
TTAGC	0.144383940326387
CGTCA	0.140668346983743
GGGTA	0.140559448794974
CGTGG	0.134170479942115
CTACG	0.134170479942115
GGTGG	0.133438085456013
GTTAG	0.133249493795218
AAAAA	0.133170344691739
TGGTT	0.133050585399332
GCGTC	0.130000643813058
TAGGA	0.128728958342207
GGAGC	0.128344254517951
GACGC	0.125782694449396
CCGTT	0.125533645090069
TGACG	0.122945093138699
TTTCT	0.121855474178757
GTCCG	0.113866383487026
GCGTG	0.113108864414286
AGGGC	0.111561530799392
AGAAT	0.111258568451936
TGAGC	0.109277927836196
CAATC	0.109263440473484
CGCCT	0.108197989763922
TCCGC	0.107895506265405
GCTTT	0.107861191018911
GTCTC	0.107075916847081
TAAAG	0.10666874655683
CGATA	0.103513530608363
TAATC	0.101940116363427
AGTCG	0.101901676469774
AGAGA	0.0988748439961036
ATTCT	0.0976162597186412
TTCTT	0.0962796044234169
TGAAG	0.0948141586755538
TTTTA	0.0939130541787958
CGCTG	0.0925065395750977
CACGC	0.0921932847609499
ACCCT	0.08627267944197
TGGTG	0.0853284704115846
GGTTA	0.0845575055838716
AAGTT	0.0842766821489443
CTGTT	0.0830686734105418
AGGTC	0.0801612717069403
CTGTG	0.0792803021494396
CTCAA	0.0781112208452093
CGACC	0.0775541961797058
ATTCA	0.0775272398485388
TAGAG	0.0766006794239527
TGAAA	0.0758731720063378
CGGCA	0.0752018476381781
TTAGT	0.072113167851472
GAGGT	0.0703872988835497
GTGTA	0.0693807754904059
GTTGG	0.0686552659669205
CCAAT	0.0656704297759193
AAAGT	0.0637488686883097
CCCGA	0.0632403104170584
GAGTG	0.0630515970208145
ATTCC	0.0582203335779393
CTCTT	0.0576580995101856
TGAGG	0.0535834856176667
AAGCG	0.0534675552836506
TGATG	0.0497454416855899
TGGGC	0.0470484998961702
TAGTG	0.0467875759903206
AATCC	0.045822269718321
CGACT	0.0456075497392072
TGTGG	0.0441939650355964
CCGTG	0.0441819746013736
CTTTG	0.0427124247636199
GAGTC	0.0412082321542124
GGAGT	0.0383577943959422
CGCAT	0.0375720894707539
TCAAA	0.0371352321774813
CTGAG	0.0369070657519436
TTTTC	0.0366421097023559
GGCGC	0.0366090729201512
AGTGT	0.0354963740733539
GAACG	0.0348137564089057
AAGAT	0.0334391928386216
GAGTA	0.0327376209381121
TTAAT	0.0321872234918359
ACGAC	0.0317299753112403
GAAGC	0.0295266088145157
ACGGG	0.0293981580250534
GTTCC	0.0289817357272023
CGCAG	0.0267033299469884
GATGT	0.0257889892936043
TTGCT	0.0249910986551121
TTTCA	0.0246562822548905
GCCCG	0.0216625092454484
ATTTA	0.0216133133224111
TTTGC	0.0200351919652183
AATCA	0.018684962131576
TTTAT	0.0168377408198272
AAGGG	0.0153575066289381
GCTCT	0.0151376799457114
CTTAG	0.0138186669132079
ATGAT	0.013507089512147
AAGCT	0.013248418031724
AGGCG	0.0123246446661122
AATGG	0.0121617494101195
AGACG	0.0104204832107867
TGTAG	0.00756817617997382
GAGGA	0.00710162263505581
TTGTA	0.00614676295493688
GGTGT	0.00394228699535577
CGGAC	0.00292594666386249
CTAAT	0.00248807446910671
CGGCT	0.00201313736995697
AAAAT	0.00156381949700917
ATGGA	0.000369848014199603
TTCTA	-0.00129334411715977
GGCGG	-0.00261223687756752
TATTG	-0.00317543449371773
CTTCC	-0.00446353054445054
TAGTT	-0.00493125748055918
ATCTA	-0.00801179418371471
TTCAG	-0.0083704845183599
CTCCT	-0.00876015953722325
GTTCA	-0.0108744256148423
CTTCA	-0.0110236120203611
CCAGA	-0.0112879125558385
CAAAT	-0.0113527064645012
GGAGG	-0.0128570505770652
CCGAG	-0.0132255659205478
AAAGG	-0.0132975938911409
AGTGA	-0.0137211578211973
GGAAA	-0.0138547511290648
TGCTT	-0.0140078904149838
TTTAA	-0.0148040880732568
GCGGC	-0.0149959613333999
TCATC	-0.0153620882747128
ATACG	-0.0169947474593978
ACTCG	-0.0169947474593978
GGGCA	-0.0182198622076862
TCTAT	-0.0206425244745421
CGTCC	-0.0207506360592072
TACGT	-0.0208315444605166
GTTGC	-0.0221133662025512
GGTCT	-0.0240610137740121
AGATG	-0.0253698642966061
TCTTT	-0.0257534864564362
TGTAA	-0.0292083989664887
AGCTG	-0.0305663840601226
ATGAA	-0.0312610156961839
CTCTA	-0.0315356374833311
ATGCG	-0.0324617847834652
GGAAG	-0.0355204887247811
ATTGC	-0.0355752227190473
TTATG	-0.0380110160434741
ATCTT	-0.03818710383648
TTAAG	-0.0389938385893288
AGGGA	-0.0396802247139974
AAGGT	-0.0410986772281356
AGAGT	-0.0428262850640291
GCTCC	-0.0436166392731677
TTCAT	-0.0458977356417383
CCTCT	-0.0465907398812604
GAAAA	-0.0468250792912201
GGTAA	-0.048980202627789
TCTCA	-0.0495658084931177
TGTAT	-0.0496024480634805
GTCAA	-0.0516161280706739
AGTTC	-0.0524375435402492
GCAAT	-0.0528209775101375
GCTTA	-0.0544047663370141
CTTTT	-0.0545320943291384
GTATC	-0.0565130816669947
CGCAA	-0.0565750650847993
GTTAA	-0.0569671520116333
TTCCT	-0.0581144228768585
CTAGA	-0.0581308859745691
TCTGC	-0.0583569182383258
TATAG	-0.060593391860491
TAGAA	-0.0636355863556268
GGGAG	-0.0641882491946744
TAACG	-0.0652067015230943
TTAAA	-0.0654704162477162
GTCTG	-0.0697264327361046
GGTCA	-0.0700266541095165
ATCAA	-0.0738747317943393
GCTTG	-0.0743337695733435
AGAAA	-0.074399634286671
GAAAG	-0.0745172974537947
ACGTT	-0.0747949095621474
GCTCA	-0.0752992206416396
ATCAG	-0.0760515004796167
CCTTC	-0.0772444020201207
GATGG	-0.0779051279491823
GTGGT	-0.0779192542218771
AAGGA	-0.0800952893114639
AGTTG	-0.0805749077732114
TGCTC	-0.082941875031097
TATGG	-0.0829617770181421
TAAGG	-0.084946809361472
TTCAC	-0.0858340572645679
GGCCG	-0.0860790593948824
TCCAA	-0.08626603386908
TGTTA	-0.0863336210619895
TCCCC	-0.0896545136187097
AAACG	-0.0901002741117809
TTTCC	-0.0928104191820169
CGACA	-0.0929984733346731
GTAAA	-0.0955048483793725
GTGTC	-0.0963962420358637
GAGGG	-0.0972107246215873
TAAAT	-0.0979775665299235
TCCTT	-0.0980029621869184
ACGTA	-0.100503642991543
CAAAA	-0.100852351412775
CTGAA	-0.101507734317218
CCTAA	-0.10153010695579
CTATG	-0.102992442331229
GTATT	-0.104891041987009
AGGAG	-0.105598510114306
GTAGC	-0.106319851832507
GGAAC	-0.106698544510636
CTCAG	-0.107479060075415
CGCTA	-0.108543275893941
CCCAA	-0.108763529532322
GAATG	-0.109256831026262
AGTAG	-0.109552615466826
CACCG	-0.109898647547932
CGTAC	-0.111201753633157
GGCTC	-0.1123438230541
ATTAA	-0.112411780535553
TAAGA	-0.112732616371407
AGGAA	-0.11311762915987
ATGTG	-0.114348004127255
TTCCC	-0.114386155100207
TTATT	-0.114974000942771
GTAGT	-0.115379833367845
TATGA	-0.115638687172146
GCCGT	-0.116834754951086
ACGGC	-0.116875575352614
GCTGA	-0.116962418252402
CGGTT	-0.117736587708759
CTTTA	-0.118570432812007
CTTTC	-0.119563711980698
GATAA	-0.119732252355718
GAAGT	-0.120742605981724
CCGTA	-0.121210353348244
ATAGA	-0.121273680340135
CGGGT	-0.121588595088504
CCACG	-0.121638521378574
GCGAC	-0.122604935419996
AGAGC	-0.122604935419996
GATAG	-0.122895772038437
AGGGG	-0.12459348851345
TCACT	-0.126338291180154
CCCAG	-0.12827562304909
GTCTT	-0.128413753763033
ATGTT	-0.128600854980021
TCTTA	-0.133513872564847
CCGGT	-0.133931353092787
ATCCA	-0.134446154171758
TTATC	-0.134984830452472
TCTAA	-0.135379870277452
ATGAG	-0.135390526617442
CTTGA	-0.135458719873427
GTATA	-0.137072771158831
TATGT	-0.138825179229171
GCTGG	-0.140198995434735
TACGC	-0.14033110431637
GAAGG	-0.145786784495705
GTTAT	-0.146065760154842
TCTAC	-0.151928154906749
GGATA	-0.154126837063967
CAAAG	-0.155029446211342
GTATG	-0.155383229516454
CGGTC	-0.157348884744731
TCAGC	-0.15869003320288
TTGAC	-0.159193535952887
TGCCG	-0.1599442972445
CGTGC	-0.160012624462343
AGGTG	-0.160273191590137
AAGAA	-0.160383343685728
CTCCA	-0.161213874482313
AATGA	-0.16127677022315
ACCCA	-0.162900486564829
ATGGT	-0.16403955013231
CGCAC	-0.16476058258245
TTGTC	-0.16487656193133
AAAGA	-0.165200663434147
GCTAG	-0.165355581989114
AGTCT	-0.166858639669001
GGCTT	-0.170787705398674
AAGAG	-0.171611657297936
AGAAG	-0.17179047413075
CTGCT	-0.174220282072523
ATTAC	-0.175466408198939
CAATG	-0.176015928135884
AGTGG	-0.177646298977958
AACGT	-0.177975831880462
AGCGT	-0.17827016711347
AGCTA	-0.178352636833384
CCTAG	-0.178494693616279
TCTTG	-0.179338080871652
CCTCC	-0.17953935139613
AAAAG	-0.180805345454524
CTTAA	-0.182855816521811
GACTC	-0.182969061188353
GGATG	-0.184123232569659
ACTTT	-0.18687057939662
CTTGT	-0.187410721524429
CTGTA	-0.188122346344204
ACCGA	-0.189928810087258
AATGT	-0.190191140129755
GATGC	-0.193463305322859
TTCCA	-0.194455220439674
AACGG	-0.195236482129828
ATCAT	-0.195313336372864
ATAAA	-0.195730108737853
CACGT	-0.195853917450635
CTCCC	-0.196583321384717
GACTT	-0.197133993672318
GACGT	-0.198137566587354
CCTTT	-0.198224086305773
TTTAC	-0.198707914505788
GTAGG	-0.199643817906037
TGTCT	-0.200155106299296
TCCAG	-0.200379635481819
CCCGG	-0.200946386701788
ATAGG	-0.202580312140592
AAATG	-0.20275429355622
ATGTA	-0.202821751287424
CTATC	-0.204211054818863
ATTAT	-0.204381809440182
CTAGT	-0.204692531699375
TGATA	-0.210501478471669
CCAAA	-0.212401605770642
ACTCT	-0.213195668752932
ATAGT	-0.213309405351875
TATCT	-0.213418339744376
ACGTC	-0.216387081740613
TAATG	-0.21753958923616
TAAAA	-0.217648516518661
GCGCC	-0.219466474672586
TGCGG	-0.220307451111956
TGCAA	-0.221634311355296
CAGCT	-0.222180221141007
TCATT	-0.223125028926298
CTGGT	-0.223129882553469
CAGAG	-0.225774727140809
GAAAC	-0.226005806684363
CAAGT	-0.226085597824664
ACGCA	-0.226425332913643
CTCAC	-0.230035295578686
CACTC	-0.230779793904348
AAACC	-0.232218585277904
GGTAG	-0.232732020238626
CTATT	-0.234498360624001
TAAGC	-0.235245072118329
TGACT	-0.23680735980625
TTACT	-0.236911710550822
TAGTA	-0.240080882874468
TCATG	-0.241909083138178
TTATA	-0.242763790398092
TGCCC	-0.243451115216323
GGGTG	-0.243544614295483
TCAAG	-0.244600781684768
TATTT	-0.245950943710661
ATCCT	-0.246070625769649
AAGTG	-0.24661822542927
TCAGT	-0.248007366714394
CAGTG	-0.248102605909777
CGGTA	-0.248721698868125
ATAAT	-0.250798475718849
GTTAC	-0.251917821518304
CAGAA	-0.252423175906953
ACGTG	-0.25299105430078
GGTAT	-0.253867519195786
GGCTA	-0.253891850421226
TGGTA	-0.254346634174747
TAGTC	-0.254420338879079
GACCG	-0.256182755956131
TGGTC	-0.256187497865296
TATAA	-0.257049895018083
TCAGG	-0.257057287695906
GTAAG	-0.260108459169931
AGAGG	-0.260108459169931
AGTAA	-0.260393774120112
GAGGC	-0.264224567642163
GCACG	-0.264666741132236
GGACG	-0.264846378176594
CATTG	-0.26801143652696
CATAG	-0.269187753080794
AAAGC	-0.269780193990774
ACCAA	-0.271684810477551
GAACA	-0.272932499527515
ACAAA	-0.273272918368379
GAACT	-0.274540340512518
CATTT	-0.276650756745857
CCCTT	-0.277267475702067
CCGCT	-0.279253508436635
ACGGT	-0.280380854196193
GAATA	-0.284088922849814
TGGCT	-0.284685268252205
ACTTG	-0.28496239213274
GTCTA	-0.286117869623847
GATAT	-0.287990317689824
ACAAT	-0.289915766197521
GCTAA	-0.290386486338294
GCCCA	-0.291257157740595
CTTGG	-0.292286346386073
CTAAA	-0.29397707681115
CACTG	-0.295317115234149
TCCAT	-0.295585337659628
TAAGT	-0.298454770819414
GAACC	-0.298582606984567
TATTC	-0.30010865854033
GCAGA	-0.300147096428379
CTACT	-0.301427225140911
TACTT	-0.302100309027599
CATGG	-0.304570993230989
ATCAC	-0.305850082167107
GCAAA	-0.306578071322227
AGGTA	-0.306582888969432
ATAAG	-0.307155382070352
AGTTA	-0.308612271300568
AGTAT	-0.308678254499578
TACCG	-0.308712888831995
TCCTG	-0.311435937546406
GTGAC	-0.312601335767775
TACTC	-0.313002117176577
CCCCA	-0.313219795629494
AACAA	-0.317024498783058
AACTT	-0.320634880179708
CATGA	-0.321446541661719
TACAA	-0.322104163482499
GAGAC	-0.322441232190271
ACTAG	-0.322470787739837
GTGGC	-0.325035095790704
GGACT	-0.326419619785983
TAGGC	-0.3271760796692
ATATA	-0.327864761547153
AAAAC	-0.329815653246362
TCCAC	-0.331695541418951
GGGCG	-0.332864801605245
TCCCA	-0.332864801605245
TCACC	-0.333222424397865
CAAGG	-0.333308689150523
TTGCA	-0.334017670080039
TGAAC	-0.334329330628778
ACAGA	-0.336591544974004
CTAAG	-0.336672912510338
CCATT	-0.337032940626343
GGTAC	-0.340396248127567
GTCAG	-0.340715216742815
GCTAT	-0.341245221895337
TTGGC	-0.341997325080214
GACAA	-0.342600660175259
AGCGC	-0.342934890299552
GGGAC	-0.345144563025731
GCTGC	-0.345641273321871
CAGCG	-0.347571300420271
AGGCT	-0.34870238243892
GAGCC	-0.349113465228677
TATAT	-0.34955646054428
AAGTC	-0.350443394722123
ATCCC	-0.35175334710138
TGTAC	-0.352188959411617
AACGC	-0.352554707934526
AAGTA	-0.352896607451902
AGAAC	-0.355346255942856
TTGCC	-0.356359850373295
TCCCT	-0.357651584792863
GAGCA	-0.358556947258026
AGCCG	-0.359050308863567
TGTGC	-0.360007029224052
CTTAT	-0.361635636057526
TATTA	-0.363102452493257
GCTGT	-0.36973295034443
AGATA	-0.371626009910817
CCAAG	-0.372269134805403
ACTGT	-0.373689709868815
AATAA	-0.37541623680567
ACACG	-0.381896939567974
GGACC	-0.38366349747421
TACCC	-0.384300604191272
ACTTC	-0.384928378848172
CCCCT	-0.387153003918898
TTACA	-0.389368201021271
TCAAC	-0.389983463103983
AAACT	-0.390135325082596
CTAGC	-0.390443107681279
ATGTC	-0.392534899728385
CATCT	-0.393489339896008
TCATA	-0.395211256475601
GTCCT	-0.395565243735099
GATAC	-0.395579404283118
CCCTC	-0.398029610666563
TCCTA	-0.398099462242257
GCATG	-0.398582369367124
TTAAC	-0.39962214771615
CCCAT	-0.399635507611701
AGCAA	-0.400239925996667
GCCCC	-0.403066413011974
CCGGG	-0.403066413011974
GTGCT	-0.404975371333353
AGCGG	-0.406265294679294
TGCTG	-0.408274542855133
CCTGA	-0.409423180936957
GTACT	-0.409470059583689
GGCAA	-0.4096475126635
ACCGG	-0.410765126907465
ATAGC	-0.411573133112225
TATCA	-0.41204632984588
GGTCC	-0.412485259401397
CCCGT	-0.413141681213471
GACTA	-0.415386684647842
GTACC	-0.416082015229648
CATGT	-0.416477429628999
ACGCT	-0.418654398481753
TCACA	-0.418654398481753
ATATG	-0.419723037036013
GCGCT	-0.422192707395061
GTCAC	-0.425234931042867
ATGGC	-0.426369005909339
AGGAC	-0.426402210165375
ACCTA	-0.42822443838037
CATCA	-0.430479080705637
AACTC	-0.431723069051281
GGCTG	-0.435871975423669
GCTAC	-0.436847146202967
GCGCA	-0.437412990977841
AATAG	-0.437477556980264
CAGGG	-0.437504710043379
TAAAC	-0.441576453954318
TTACC	-0.442421808505304
TGGAC	-0.444533030307359
CACAG	-0.44576638687684
TACTA	-0.446669624915745
GGTGC	-0.447167807394099
CTATA	-0.447548707432658
TAGAC	-0.447856585260801
GACCT	-0.448115819595702
CAGTT	-0.449350630017223
CCCAC	-0.450484950051358
CTTAC	-0.453670888813485
CACTT	-0.453984820826981
ACTGG	-0.454035450701441
TGTCA	-0.454895103359827
ACAAG	-0.454898808943884
TATAC	-0.455709274759372
ATATT	-0.455931632317112
CATAA	-0.456132673727494
AGACT	-0.456471293033117
TGCTA	-0.456979074780271
CACAC	-0.457896840388287
GCAAG	-0.459481723778511
ATGCT	-0.46080580940706
CACTA	-0.461372208731373
CTTGC	-0.461883112282788
GCGGG	-0.463392057558675
GACTG	-0.463582157587696
GTAAC	-0.464623389776124
AATGC	-0.466086700157116
CAAGA	-0.471205701493723
TACTG	-0.472188506070242
AATAT	-0.474439360583214
AGTCA	-0.476604396529199
AAGGC	-0.478531978303434
CTGTC	-0.479233166672468
CTACA	-0.480892345340427
CTCAT	-0.482995208090756
CCTCA	-0.484168736230736
CACAA	-0.486284504602373
CCATG	-0.486384314993607
ACTCA	-0.487569440638288
TATGC	-0.48834175909544
CCTTA	-0.48965078322558
GCCTC	-0.490040769976521
GCCAA	-0.490871046264722
CCTAT	-0.492007966250755
ACTAC	-0.494371829040379
ACTGA	-0.495701384718114
TAATA	-0.495726178617851
AACCT	-0.497198608987726
GACCC	-0.498378625010384
TGCAT	-0.499225294915397
CATTA	-0.499871715763389
GCCTT	-0.503741106348182
TACAT	-0.505207426264732
GGGGC	-0.505415272454381
AAATA	-0.505464156918917
CACGG	-0.507120847279383
GTGCA	-0.50897309186757
CAGGA	-0.513966218628749
ACCGT	-0.514681286255529
GGCAG	-0.517210534794027
AGCAG	-0.51746455276121
GACCA	-0.517793472322878
CCACA	-0.518671369156648
ACTAA	-0.521812536726635
GCATT	-0.522388570981521
GGACA	-0.522397478760903
CAATA	-0.523774882594819
ATGCA	-0.523793540323793
CAAGC	-0.524127976029293
ACATT	-0.525187279607929
GGCCA	-0.528041664416565
GCCAT	-0.528995591249163
CCTTG	-0.529472855005267
AGCCA	-0.538543837440373
ATACA	-0.540471971425766
TGACC	-0.541394569559948
AAACA	-0.543128026721186
CCATC	-0.543740735901105
ACCTC	-0.544525077556013
CACCA	-0.544723395589238
ATGAC	-0.546831222784232
GCATC	-0.547472194365466
CCACT	-0.549968357714696
AGTCC	-0.550284074772865
AACCA	-0.554243263634952
CAAAC	-0.554856241275789
CCGCA	-0.556157922231688
ATATC	-0.557854039478724
ACTTA	-0.564176277306848
TATCC	-0.564694275479488
GTACA	-0.566769797403983
TACAG	-0.56686611941594
AAGAC	-0.567395495121552
TACCA	-0.569105496636929
AGACC	-0.569917624108707
TAACC	-0.572112188335296
TGCGC	-0.575463900133807
TAGCA	-0.576032051862681
AGGCA	-0.578484574320773
CAGTC	-0.578597470090523
TGTCC	-0.579784981160346
ACTAT	-0.579819107566953
CAACA	-0.58122922608945
GTCAT	-0.582036554057293
GCCAC	-0.582036554057294
AGTAC	-0.582713716726796
TAACT	-0.583839923093219
ACACT	-0.584944481554052
AACAG	-0.587282723623253
GCGGT	-0.588162656854135
ACCTT	-0.588803164269448
CGGGC	-0.59309174256629
CCATA	-0.593289351106787
AACTA	-0.593303175505819
CATCC	-0.595413151493888
ACACA	-0.600881369127938
CAGGT	-0.602295393041094
CATTC	-0.604553990618721
AAGCC	-0.617779739141801
ACAGT	-0.617783063749074
TGCCT	-0.618598497007595
CCCCC	-0.618795104067412
TGGCC	-0.62267853855464
CTGCA	-0.627041256045611
GGCAT	-0.6285255719325
AAGCA	-0.630708287215777
CAGTA	-0.634901068033669
ATAAC	-0.636364990067841
GCAGT	-0.638953306825394
AGACA	-0.640174990108816
CATAT	-0.640275014556355
CAACT	-0.642624162729505
CACAT	-0.645239341355423
TACAC	-0.645251849060956
ATACT	-0.645335646892835
GCAGC	-0.647893636196478
ACAAC	-0.649382862383693
GCAAC	-0.649532701568123
CAGAC	-0.651828368980578
CTACC	-0.653674428145951
CCTGT	-0.657033663064235
ACATG	-0.657743805474551
GTCCA	-0.658139533143085
GGCCT	-0.658370245697949
TGCAG	-0.658775997341004
ACATA	-0.659325440966376
TACCT	-0.668979241072995
AATAC	-0.672613500214558
GACAT	-0.676713253595736
GCCTA	-0.678324869116283
TGACA	-0.680116675064136
GCCCT	-0.682640494995699
TAACA	-0.683420348427699
GTGCC	-0.683627435203866
ATGCC	-0.687302020754713
CCTGG	-0.688033201445446
CCACC	-0.688835312996876
AACAC	-0.689015465776288
TAGCC	-0.69004374367566
AGTGC	-0.692666057491793
ACTCC	-0.69481871015715
GCATA	-0.698201553441526
CCAGG	-0.699340463461568
AACTG	-0.700096845226654
ACCAT	-0.700192977530895
CCAAC	-0.702898875805731
AACAT	-0.704142217287306
AACCG	-0.715303084920758
GACAC	-0.727992907673275
AGGCC	-0.734039647502344
CAACC	-0.735606942649304
ACCAG	-0.736990177207164
GTCCC	-0.740590311350159
CCAGT	-0.742870449846628
CCCTG	-0.75653428528943
CCTAC	-0.756614732220663
CATGC	-0.759195835923889
AGCAT	-0.77075592878589
ATACC	-0.77399934537506
AGCCT	-0.784399601515345
ACATC	-0.794087031172283
CATAC	-0.803481081114643
ACCCC	-0.813852229280367
GCACA	-0.814455592653003
CCAGC	-0.817140027143296
CTGAC	-0.82351239453199
AGCCC	-0.856211517496288
TGCAC	-0.858048813889297
CACCT	-0.858684771254162
CTAAC	-0.863419649089267
GGGCC	-0.868340739213935
ACCAC	-0.86900562012702
TGCCA	-0.871331616879748
GCACT	-0.878623519602114
TGGCA	-0.881108035287813
CCTGC	-0.890322040985988
GCAGG	-0.89300543695479
GACAG	-0.899328238823937
ACCTG	-0.908181003745726
AGCAC	-0.911616456560516
CTGGC	-0.913242462532667
CAGCA	-0.921988330779983
GGCCC	-0.93104418300094
GCCTG	-0.961228854389415
CACCC	-0.989775971344123
ACAGC	-0.997922447974458
ACTGC	-0.998004524210628
CAGGC	-1.00157544557108
ACCGC	-1.01697361077384
ACCCG	-1.01886274210142
ACACC	-1.05540736365246
GGCAC	-1.08767660211704
CAGCC	-1.09113228712117
ACAGG	-1.16699905477845
CTGCC	-1.22214060897091
GCCAG	-1.24404009054228
GCACC	-1.25559297804744