#!/usr/bin/perl -w

package runyinoyang;

use strict;
use IO::File;

use base 'Exporter'; 
our @EXPORT = qw/runyinoyang/;

use formatAlleleSeq;

#http://www.cbs.dtu.dk/services/YinOYang/output.php
# size max protein: 4000 amino acids!!!!

#For each sequence, this function will create a new file : Mitoprot work with only one sequence in one file.
sub runyinoyang($$$$$$$){
	
	my ($delta,$workpath,$outpath,$infile,$execommand,$encodingfile,$BASE_SEQ_NAME) = @_;
				
	my @args = ();
	my ($name,$seq,$seqname,$fh_temp,$outfile,$len);
	
	print "infile:$infile\n";
	
	my $prog = "yinoyang";
	
	my $input_file = "temp-".$prog.".fasta";
	my $output_file = "temp-".$prog.".".$prog;
	
	# get the names of the parameter files
	my ($command) = $execommand =~ /\/([^\/]+)$/;
	
	# get the base name of the input file to create the ouput file name
	($outfile) = $infile =~ /\/([^\/]+)$/;
	$outfile =~ s/\..*/_$prog\_results.res/;
	$outfile = $outpath."/".$outfile;
	print "OUTFILE: $outfile\n";
	
	# create the symbolic links for the executable to the working directory
	# otherwise the resulting file cannot be obtained
	@args = ("ln", "-s", $execommand, "$workpath/.");
	unless (-e "$workpath/$command") {system(@args) == 0 or die "system @args failed: $?"};
	
	# go to the working directory to run the command
	chdir "$workpath" or die "cannot change dir runyinoyang::runyinoyang chdir $workpath : $?";
	
	# get the encoing information
	my ($h_encodingName,$h_encodingID,$h_name_allele,$h_name_position,$h_name_var_type) = getEncoding($encodingfile);
	
	# open the input and output files	
	my $fh_in = new IO::File $infile || die "Can not open file $infile : $!";#Data
	my $fh_out = new IO::File ">>$workpath/$prog\_results.txt" || die "Can not create the result file (mitoprot) $workpath/$prog\_results.txt: $! \n";
	
		
	while($name = <$fh_in>){
		
		# check teh fasta format
		print "$name\n";
		if($name =~ /^>.*/){
						
			$fh_temp = new IO::File ">$workpath/temp-$prog.fasta" || die "Can not create $workpath/temp-$prog.fasta: $! \n";			
			print $fh_temp $name;#print the name of the SNP			
			$seq = <$fh_in>;			
			
			$len = length($seq);
			
			if($len >= 21 && $len <= 4000){
				
				print $fh_temp $seq;#Print the sequence of the SNP
				$fh_temp->close();				

				# RUN the program in the working dir
				# the output file is localized where the command is launched (!?)						
				@args = ("$workpath/$command", "$workpath/$input_file" , ">", "$workpath/$output_file");
				system("$workpath/$command $workpath/$input_file > $workpath/$output_file") ;# == 0 or die "system @args failed runyinoyang: $?";
										
				#~ @args = ("rm", "-f", "$workpath/temp-mitoprot.fasta");
				#~ system(@args) == 0 or die "system @args failed: $?";
				
				# generate an ouput file with results from mitoprot concatenated
				extract_yinoyang_results("$workpath/$output_file",$fh_out,$BASE_SEQ_NAME,$h_name_var_type);			
			}
			else{
				
				print "$name : protein size too long : $len => not analysed\n";
			}
		}
		else{
			
			print "Error file format not correct runyinoyang::runyinoyang: $infile should be fasta format\n";
		}
	}
	$fh_in->close();
	$fh_out->close();
	
	#############################################################
	# compare results for the 2 alleles and interpret the results
	
	getyinoyangVariations($delta,"$workpath/$prog\_results.txt",$h_encodingID,$h_encodingName,$h_name_position,$h_name_allele,$outfile,"$outpath/$prog\_title.txt",$h_name_var_type,$h_name_allele);
}


# Concatenation 
sub extract_yinoyang_results($$$$){	
	
	my ($resfile, $fh_out, $BASE_SEQ_NAME,$h_name_var_type) = @_;
	
	my $prog="yinoyang";
	
	my ($name,$position,$signal,$score);
	
	my $fh_in = new IO::File $resfile || die "Can not open the output file of $prog $resfile : $! \n";
	
	while(<$fh_in>){
		
		if($_ =~ m/^$BASE_SEQ_NAME\d+\s*\d*\s*\S*\s*\S*\s*\S*/){
		
			($name,$position,$signal,$score) = $_ =~/^([^\s]*)\s*(\d*)\s*\S*\s*(\S*)\s*(\S*)/;				
			
			if($h_name_var_type->{$name} eq "snp"){ ###
			
				print $fh_out "$name\t$position\t$signal\t$score\n";
			}
		}					
	}	
	$fh_in->close();
}



#Find the transcript who win/lost phosphorylation signal
sub getyinoyangVariations($$$$$$$$){
	
	my ($delta,$infile,$h_encodingID,$h_encodingName,$h_name_position,$h_name_allele,$outfile,$titlefile,$h_name_var_type,$h_name_allele)) = @_;		
	
	my $fh_in = new IO::File $infile || die "Can not open nrunyinoyang::getyinoyangVariations : $infile : $! \n";
	my $fh_out = new IO::File ">$outfile" || die "Can not open $outfile : $! \n";
	

	my ($line,$allele,$pos,$enzyme,$score,$name,$seq_name,$signal,$basis_name,$key_name,$diff_score);
	my ($nameA1,$nameA2,$score_diff);
	my ($start,$end,$ref,$alt,$info,$end_alt,$i);
	
	
	my %score_allele1 = (); # key: seq_name
	my %score_allele2 = ();
	my %signal_allele1 = ();	
	my %signal_allele2 = ();
	
	my %seq_list = ();
	
	my %netcglyc_res = ();
	my %change_position = ();
	
	my @tab1 = "";
	my @tab2 = "";
	my $c = 2;
	
	my %ref_pos = ();
	my %alt_pos = ();
	
	while($line=<$fh_in>){
		
		# get the information		
		($seq_name,$pos,$signal,$score) = $line =~ /([^\t]*)\t([^\t]*)\t([^\t]*)\t([^\n]*)/;
				
		# check that the id is existing
		if(defined $h_encodingID->{$seq_name}){
			
			($basis_name,$allele) = $h_encodingID->{$seq_name} =~ /(.*)_(allele\d)$/;
			
			if($h_name_var_type->{$seq_name} eq "snp"){ ###
			
				if($pos eq $h_name_position->{$seq_name}){
					
					if($h_name_allele->{$seq_name} eq "allele1"){
						
						$signal_allele1{$basis_name} = $signal;
						$score_allele1{$basis_name} = $score;
						
					}
					elsif($h_name_allele->{$seq_name} eq "allele2"){
						
						$signal_allele2{$basis_name} = $signal;
						$score_allele2{$basis_name} = $score;
						print "$basis_name : $signal_allele2{$basis_name} - $score_allele2{$basis_name}\n\n";
					}
					else{
					
						print "PB: $seq_name : $basis_name:$h_name_allele->{$seq_name} function nrunyinoyang::getyinoyangVariations\n";	
						exit(12);
					}				
				}				
			}	
			# INDELS
			else{
								
				# get the [REF/ALT-POS] information
				#~ print "$h_encodingID->{$name}\n";
				($info) = $h_encodingID->{$seq_name} =~  /\[([^\/]+\/.+\-\d*\-*\d+)\]_allele\d*/;
				
				# retrives the amino acids to check on					
				($start,$end,$end_alt) = analyseIndelChange($info);
				
				#~ print "coordinates: $start,$end,$end_alt\nPOSITION: $pos\n";
				
				# get the signals from the reference
				%ref_pos = ();															
				for($i=$start;$i<=$end;$i++){
					
					$ref_pos{$i} = "";						
					#~ print "ref:$i\n";		
				}
				
				# get the signals from the alternative
				%alt_pos = ();															
				for($i=$start;$i<=$end_alt;$i++){
					
					$alt_pos{$i} = "";											
					#~ print "alt:$i\n";
				}
						
				print "--> POS FROM RES: $pos\n";							
				
				if((defined $ref_pos{$pos}) and ($h_name_allele->{$seq_name} eq "allele1")){							
			
					$score_allele1{$basis_name} = "indel";	
					
					if(not defined $signal_allele1{$basis_name}){
						
						$signal_allele1{$basis_name} = 1;
					}
					else{
								
						$signal_allele1{$basis_name} = $signal_allele1{$basis_name} + 1; # number of signals on the reference for the indel
					}
					
					print "REF:$basis_name:$signal_allele1{$basis_name}\n";
				}
				
				if((defined $alt_pos{$pos}) and ($h_name_allele->{$seq_name} eq "allele2")){
					
					$score_allele2{$basis_name} = "indel";			
					
					if(not defined $signal_allele2{$basis_name}){
						
						$signal_allele2{$basis_name} = 1;
					}
					else{
						$signal_allele2{$basis_name} = $signal_allele2{$basis_name} + 1;	# number of signals on the alternative for the indel		
					}
					
					print "ALT:$basis_name:$signal_allele2{$basis_name}\n";
				}				
			}
		}
		else{
			
			print "PB: No encoding name for *$seq_name* in runyinoyang::getyinoyangVariations\n";
			exit(11);
		}
	}
	$fh_in->close();
	
	
	# analyse the information
	# to analyse the difference between the 2 alleles
	my $fh_title = new IO::File ">$titlefile" || die "Can not open $titlefile : $! \n";
	print $fh_title ("Sequence Name\tCase\tscore allele1\tscore allele 2\tsignal allele 1\tsignal allele 2\n");	
	$fh_title->close();
	
	foreach $basis_name (keys %signal_allele1){
				
		#~ ($basis_name) = $h_encodingID->{$seq_name} =~ /(.*)_allele\d$/;		
		
		#~ $nameA1 = $seq_name;
		#~ $name = $h_encodingID->{$seq_name};
		#~ $name =~ s/allele1/allele2/;		
		#~ $nameA2 = $h_encodingName->{$name};
		
		if($score_allele1{$basis_name} eq "indel" ){
			
			print "$basis_name : $signal_allele1{$basis_name} != $signal_allele2{$basis_name}\n";
			
			# the number of signals is different between reference and alternative at the indel part 
			if ($signal_allele1{$basis_name} != $signal_allele2{$basis_name}){
				
				print $fh_out ("$basis_name\tdiff\t$signal_allele1{$basis_name}\t$signal_allele2{$basis_name}\n");
			}
			delete $signal_allele2{$basis_name};
		}
		# snp
		else{
		
			if(not defined $signal_allele2{$basis_name}){
			
				print $fh_out ("$basis_name\tloss\t$score_allele1{$basis_name}\t\t$signal_allele1{$basis_name}\t\n");
			}
			else{
				
				$score_diff = $score_allele1{$basis_name} - $score_allele2{$basis_name};
				$score_diff =~ s/-//;
				
				if($score_diff >= $delta && $score_allele1{$basis_name} > $score_allele2{$basis_name}){
									
					print $fh_out ("$basis_name\tloss?\t$score_allele1{$basis_name}\t$score_allele2{$basis_name}\t$signal_allele1{$basis_name}\t$signal_allele2{$basis_name}\n");
				}
				elsif($score_diff >= $delta && $score_allele1{$basis_name} < $score_allele2{$basis_name}){
					
					print $fh_out ("$basis_name\tgain?\t$score_allele1{$basis_name}\t$score_allele2{$basis_name}\t$signal_allele1{$basis_name}\t$signal_allele2{$basis_name}\n");
					
				}
			}
			
			delete $signal_allele2{$basis_name};
		}
	}
	
	
	foreach $basis_name (keys %signal_allele2){
		
		#~ ($basis_name) = $h_encodingID->{$seq_name} =~ /(.*)_allele\d$/;		
		#~ 
		#~ $nameA2 = $seq_name;
		#~ $name = $h_encodingID->{$seq_name};
		#~ $name =~ s/allele2/allele1/;
		#~ $nameA1 = $h_encodingName->{$name};
						
		if(not defined $signal_allele1{$basis_name}){
		
			print $fh_out ("$basis_name\tgain\t\t$score_allele2{$basis_name}\t\t$signal_allele2{$basis_name}\n");
		}
		else{
			
			$score_allele1{$basis_name} =~ s /\,/\./;
			$score_allele2{$basis_name} =~ s /\,/\./;
			
			$score_diff = $score_allele1{$basis_name} - $score_allele2{$basis_name};
			$score_diff =~ s/-//;
			
			if($score_diff >= $delta && $score_allele1{$basis_name} > $score_allele2{$basis_name}){
								
				print $fh_out ("$basis_name\tloss?\t$score_allele1{$basis_name}\t$score_allele2{$basis_name}\t$signal_allele1{$basis_name}\t$signal_allele2{$basis_name}\n");
			}
			elsif($score_diff >= $delta && $score_allele1{$basis_name} < $score_allele2{$basis_name}){
				
				print $fh_out ("$basis_name\tgain?\t$score_allele1{$basis_name}\t$score_allele2{$basis_name}\t$signal_allele1{$basis_name}\t$signal_allele2{$basis_name}\n");
			}
		}		
	}
	

	$fh_out->close();
}












#~ #For each sequence, this function will create a new file : YinOYang work with only one sequence in one file.
#~ sub init($$$){
	#~ my ($delta, $path, $date) = @_;
	#~ print "Running YinOYang.\n";
	#~ unless (-e "$path/results/YinOYang"){
		#~ system("mkdir results/YinOYang");
	#~ }
	#~ my $sub = new IO::File "fic/sub_$date" || die "Can not open file sub : $!\n";
	#~ my $i = 1;
	#~ while(<$sub>){
		#~ if($_ =~ /^>(.*)/){
			#~ my $temp = new IO::File ">fic/temp-yinoyang_$date" || die "Can not create fic/temp-yinoyang_$date : $! \n";
			#~ my $name = $1;
			#~ print $temp ">@"."$name\n";
			#~ $_ =<$sub>;
			#~ print $temp $_;
			#~ $temp->close();
			#~ system("mv fic/temp-yinoyang_$date $path/Programmes/YinOYang/yinOyang-1.2");#Move file for run YinOYang
			#~ chdir "$path/Programmes/YinOYang/yinOyang-1.2";
			#~ `./yinOyang temp-yinoyang_$date >results-yinoyang_$date`;
			#~ system("rm -f tempfile");#Clean
			#~ my $temp2 = new IO::File "results-yinoyang_$date" || die "Can not open the result file of YinOYang : $! \n";
			#~ my $res = new IO::File ">>$path/results/YinOYang/yinoyang_$date" || die "Can not create the result file (yinoyang) : $! \n";
			#~ while(<$temp2>){
				#~ extract_results($res);
			#~ }
			#~ $temp2->close();
			#~ $res->close();
			#~ #system("mv tempfile.tmp $path/results/YinOYang/seq$i");#Rename and replace file (optional)
			#~ $i++;
			#~ chdir "$path";
		#~ }
		#~ else{
			#~ print "Error\n";
		#~ }
	#~ }
	#~ $sub->close();
	#~ search_var($delta,$path,$date);
#~ }
#~ 
#~ #Concatenation in results/YinOYang/yinoyang
#~ sub extract_results($){
	#~ my $res = shift;
	#~ if($_ =~ m/^__(\d*)\s*(\d*)\s*\S*\s*(\S*)\s*(\S*)/){
		#~ my $name = $1;
		#~ my $position = $2;
		#~ my $agree = $3;
		#~ my $score = $4;
		#~ print $res ">$name $position $score $agree\n";
	#~ }
#~ }
#~ 
#~ sub search_var($$$){
	#~ my ($delta, $path, $date) = @_;
	#~ 
	#~ my $sav = new IO::File "fic/sav_$date" || die "Can not open sav_$date : $! \n";
	#~ my %id;#Hash with all name / id
	#~ while(<$sav>){
		#~ if($_ =~ m/^>(\S*)\s*(.*)/){
			#~ $id{$2} .= $1;
		#~ }
	#~ }
	#~ $sav->close();
	#~ 
	#~ my $tmp = new IO::File "$path/results/YinOYang/yinoyang_$date" || die "$! \n";
	#~ my $yinoyang = new IO::File ">$path/results/programs/yinoyang_$date" || die "$! \n";
	#~ my @tab1 = "";
	#~ my @tab2 = "";
	#~ my $allele = "";
	#~ my $c = 2;
	#~ while(<$tmp>){
		#~ my $line = $_;
		#~ if($line =~ s/^>(\d*)/$id{$1}/){#Substitute the ID by his coresponding name
			#~ if($line =~ m/(\S*)_allele(\d)\s(\d*)\s(\S*)\s(\S*)/){
				#~ if($2 eq $allele){
					#~ if($c == 0){#Same allele1
						#~ $allele = $2;
						#~ my $position = $3;
						#~ my $score = $4;
						#~ if($5 =~ m/\++/){
							#~ push(@tab1,$position,$score);
						#~ }
					#~ }
					#~ elsif($c == 1){#Same allele2
						#~ $allele = $2;
						#~ my $position = $3;
						#~ my $score = $4;
						#~ if($5 =~ m/\++/){
							#~ push(@tab2,$position,$score);
						#~ }
					#~ }
				#~ }
				#~ else{
					#~ if($c == 0){#Other allele
						#~ $c++;
						#~ my $name = $1;
						#~ $allele = $2;
						#~ my $position = $3;
						#~ my $score = $4;
						#~ push(@tab2,$name);
						#~ if($5 =~ m/\++/){
							#~ push(@tab2,$position,$score);
						#~ }
					#~ }
					#~ elsif($c == 1){#Other transcript
						#~ compare($yinoyang,$delta,\@tab1,\@tab2);
						#~ @tab1 = "";#Clean tab1
						#~ @tab2 = "";#Clean tab2
						#~ my $name = $1;
						#~ $allele = $2;
						#~ my $position = $3;
						#~ my $score = $4;
						#~ push(@tab1,$name);
						#~ if($5 =~ m/\++/){
							#~ push(@tab1,$position,$score);
						#~ }
						#~ $c = 0;
					#~ }
					#~ elsif($c == 2){#Initialisation
						#~ my $name = $1;
						#~ $allele = $2;
						#~ my $position = $3;
						#~ my $score = $4;
						#~ push(@tab1,$name);
						#~ if($5 =~ m/\++/){
							#~ push(@tab1,$position,$score);
						#~ }
						#~ $c = 0;
					#~ }
				#~ }
			#~ }
		#~ }
	#~ }
	#~ compare($yinoyang,$delta,\@tab1,\@tab2);#For the last transcript
	#~ $tmp->close();
	#~ $yinoyang->close();
#~ }
#~ 
#~ sub compare{
	#~ my ($yinoyang,$delta,$ref1,$ref2) = @_;
	#~ my @tab1 = @$ref1;
	#~ my @tab2 = @$ref2;
	#~ my $j = 2;
	#~ for(my $i = 2; $i<$#tab1+1; $i=$i+2){
		#~ if(defined($tab1[$i]) && defined($tab2[$j])){
			#~ if($tab1[$i] == $tab2[$j]){#Same position
				#~ my $diffscore = $tab1[$i+1] - $tab2[$j+1];
				#~ if($diffscore >= $delta){
					#~ print $yinoyang "$tab1[1] : Signal lost at position $tab1[$i]. Score allele 1 = $tab1[$i+1] - Score allele 2 = $tab2[$j+1]\n";
				#~ }
				#~ elsif($diffscore <= -$delta){
					#~ print $yinoyang "$tab1[1] : Signal gain at position $tab1[$i]. Score allele 1 = $tab1[$i+1] - Score allele 2 = $tab2[$j+1]\n";
				#~ }
			#~ }
			#~ elsif($tab1[$i] > $tab2[$j]){
				#~ print $yinoyang "$tab1[1] : Signal gain at position $tab2[$j]. Score : $tab2[$j+1]\n";
				#~ $i = $i-2;#Stay in same column tab1
			#~ }
			#~ elsif($tab1[$i] < $tab2[$j]){
				#~ print $yinoyang "$tab1[1] : Signal lost at position $tab1[$i]. Score : $tab1[$i+1]\n";
				#~ $j = $j-2;#Stay in same column tab2
			#~ }
			#~ $j=$j+2;
		#~ }
	#~ }
	#~ $j=0;
#~ }

1;