# $Id: SiteMatrix.pm 16123 2009-09-17 12:57:27Z cjfields $ #--------------------------------------------------------- =head1 NAME Bio::Matrix::PSM::SiteMatrix - SiteMatrixI implementation, holds a position scoring matrix (or position weight matrix) and log-odds =head1 SYNOPSIS use Bio::Matrix::PSM::SiteMatrix; # Create from memory by supplying probability matrix hash # both as strings or arrays # where the frequencies $a,$c,$g and $t are supplied either as # arrayref or string. Accordingly, lA, lC, lG and lT are the log # odds (only as arrays, no checks done right now) my ($a,$c,$g,$t,$score,$ic, $mid)=@_; #or my ($a,$c,$g,$t,$score,$ic,$mid)=('05a011','110550','400001', '100104',0.001,19.2,'CRE1'); #Where a stands for all (this frequency=1), see explanation bellow my %param=(-pA=>$a,-pC=>$c,-pG=>$g,-pT=>$t, -lA=>$la, -lC=>$lc,-lG=>$lg,-lT=>$l, -IC=>$ic,-e_val=>$score, -id=>$mid); my $site=Bio::Matrix::PSM::SiteMatrix->new(%param); #Or get it from a file: use Bio::Matrix::PSM::IO; my $psmIO= Bio::Matrix::PSM::IO->new(-file=>$file, -format=>'transfac'); while (my $psm=$psmIO->next_psm) { #Now we have a Bio::Matrix::PSM::Psm object, # see Bio::Matrix::PSM::PsmI for details #This is a Bio::Matrix::PSM::SiteMatrix object now my $matrix=$psm->matrix; } # Get a simple consensus, where alphabet is {A,C,G,T,N}, # choosing the character that both satisfies a supplied or default threshold # frequency and is the most frequenct character at each position, or N. # So for the position with A, C, G, T frequencies of 0.5, 0.25, 0.10, 0.15, # the simple consensus character will be 'A', whilst for 0.5, 0.5, 0, 0 it # would be 'N'. my $consensus=$site->consensus; # Get the IUPAC ambiguity code representation of the data in the matrix. # Because the frequencies may have been pseudo-count corrected, insignificant # frequences (below 0.05 by default) are ignored. So a position with # A, C, G, T frequencies of 0.5, 0.5, 0.01, 0.01 will get the IUPAC code 'M', # while 0.97, 0.01, 0.01, 0.01 will get the code 'A' and # 0.25, 0.25, 0.25, 0.25 would get 'N'. my $iupac=$site->IUPAC; # Getting/using regular expression (a representation of the IUPAC string) my $regexp=$site->regexp; my $count=grep($regexp,$seq); my $count=($seq=~ s/$regexp/$1/eg); print "Motif $mid is present $count times in this sequence\n"; =head1 DESCRIPTION SiteMatrix is designed to provide some basic methods when working with position scoring (weight) matrices, such as transcription factor binding sites for example. A DNA PSM consists of four vectors with frequencies {A,C,G,T}. This is the minimum information you should provide to construct a PSM object. The vectors can be provided as strings with frequenciesx10 rounded to an int, going from {0..a} and 'a' represents the maximum (10). This is like MEME's compressed representation of a matrix and it is quite useful when working with relational DB. If arrays are provided as an input (references to arrays actually) they can be any number, real or integer (frequency or count). When creating the object you can ask the constructor to make a simple pseudo count correction by adding a number (typically 1) to all positions (with the -correction option). After adding the number the frequencies will be calculated. Only use correction when you supply counts, not frequencies. Throws an exception if: You mix as an input array and string (for example A matrix is given as array, C - as string). The position vector is (0,0,0,0). One of the probability vectors is shorter than the rest. Summary of the methods I use most frequently (details bellow): iupac - return IUPAC compliant consensus as a string score - Returns the score as a real number IC - information content. Returns a real number id - identifier. Returns a string accession - accession number. Returns a string next_pos - return the sequence probably for each letter, IUPAC symbol, IUPAC probability and simple sequence consenus letter for this position. Rewind at the end. Returns a hash. pos - current position get/set. Returns an integer. regexp - construct a regular expression based on IUPAC consensus. For example AGWV will be [Aa][Gg][AaTt][AaCcGg] width - site width get_string - gets the probability vector for a single base as a string. get_array - gets the probability vector for a single base as an array. get_logs_array - gets the log-odds vector for a single base as an array. New methods, which might be of interest to anyone who wants to store PSM in a relational database without creating an entry for each position is the ability to compress the PSM vector into a string with losing usually less than 1% of the data. this can be done with: my $str=$matrix->get_compressed_freq('A'); or my $str=$matrix->get_compressed_logs('A'); Loading from a database should be done with new, but is not yest implemented. However you can still uncompress such string with: my @arr=Bio::Matrix::PSM::_uncompress_string ($str,1,1); for PSM or my @arr=Bio::Matrix::PSM::_uncompress_string ($str,1000,2); for log odds =head1 FEEDBACK =head2 Mailing Lists User feedback is an integral part of the evolution of this and other Bioperl modules. Send your comments and suggestions preferably to one of the Bioperl mailing lists. Your participation is much appreciated. bioperl-l@bioperl.org - General discussion http://bioperl.org/wiki/Mailing_lists - About the mailing lists =head2 Support Please direct usage questions or support issues to the mailing list: I rather than to the module maintainer directly. Many experienced and reponsive experts will be able look at the problem and quickly address it. Please include a thorough description of the problem with code and data examples if at all possible. =head2 Reporting Bugs Report bugs to the Bioperl bug tracking system to help us keep track the bugs and their resolution. Bug reports can be submitted via the web: http://bugzilla.open-bio.org/ =head1 AUTHOR - Stefan Kirov Email skirov@utk.edu =head1 CONTRIBUTORS Sendu Bala, bix@sendu.me.uk =head1 APPENDIX The rest of the documentation details each of the object methods. Internal methods are usually preceded with a _ =cut # Let the code begin... package Bio::Matrix::PSM::SiteMatrix; use strict; use base qw(Bio::Root::Root Bio::Matrix::PSM::SiteMatrixI); =head2 new Title : new Usage : my $site=Bio::Matrix::PSM::SiteMatrix->new(-pA=>$a,-pC=>$c, -pG=>$g,-pT=>$t, -IC=>$ic, -e_val=>$score, -id=>$mid); Function: Creates a new Bio::Matrix::PSM::SiteMatrix object from memory Throws : If inconsistent data for all vectors (A,C,G and T) is provided, if you mix input types (string vs array) or if a position freq is 0. Returns : Bio::Matrix::PSM::SiteMatrix object Args : -pA => vector with the frequencies or counts of A -pC => vector for C -pG => vector for G -pt => vector for T -lA => vector for the log of A -lC => vector for the log of C -lG => vector for the log of G -lT => vector for the log of T -IC => real number, the information content of this matrix -e_val => real number, the expect value -id => string, an identifier -width => int, width of the matrix in nucleotides -sites => int, the number of sites that went into this matrix -model => hash ref, background frequencies for A, C, G and T -correction => number, the number to add to all positions to achieve psuedo count correction (default 0: no correction) NB: do not use correction when your input is frequences! -accession_number => string, an accession number Vectors can be strings of the frequencies where the frequencies are multiplied by 10 and rounded to the nearest whole number, and where 'a' is used to denote the maximal frequency 10. There should be no punctuation (spaces etc.) in the string. For example, 'a0501'. Alternatively frequencies or counts can be represented by an array ref containing the counts, frequencies or logs as any kind of number. =cut sub new { my ($class, @args) = @_; my $self = $class->SUPER::new(@args); my $consensus; # Too many things to rearrange, and I am creating simultanuously >500 # such objects routinely, so this becomes performance issue my %input; while (@args) { (my $key = shift @args) =~ s/-//g; #deletes all dashes (only dashes)! $input{$key} = shift @args; } $self->{_position} = 0; $self->{IC} = $input{IC}; $self->{e_val} = $input{e_val}; $self->{width} = $input{width}; $self->{logA} = $input{lA}; $self->{logC} = $input{lC}; $self->{logG} = $input{lG}; $self->{logT} = $input{lT}; $self->{sites} = $input{sites}; $self->{id} = $input{id} || 'null'; $self->{correction} = $input{correction} || 0; $self->{accession_number} = $input{accession_number}; return $self unless (defined($input{pA}) && defined($input{pC}) && defined($input{pG}) && defined($input{pT})); # This should go to _initialize? # Check for input type- no mixing alllowed, throw ex if (ref($input{pA}) =~ /ARRAY/i ) { $self->throw("Mixing matrix data types not allowed: C is not reference") unless(ref($input{pC})); $self->throw("Mixing matrix data types not allowed: G is not reference") unless (ref($input{pG})); $self->throw("Mixing matrix data types not allowed: T is not reference") unless (ref($input{pT})); $self->{probA} = $input{pA}; $self->{probC} = $input{pC}; $self->{probG} = $input{pG}; $self->{probT} = $input{pT}; } else { $self->throw("Mixing matrix data types not allowed: C is reference") if (ref($input{pC})); $self->throw("Mixing matrix data types not allowed: G is reference") if (ref($input{pG})); $self->throw("Mixing matrix data types not allowed: T is reference") if (ref($input{pT})); $self->{probA} = [split(//,$input{pA})]; $self->{probC} = [split(//,$input{pC})]; $self->{probG} = [split(//,$input{pG})]; $self->{probT} = [split(//,$input{pT})]; for (my $i=0; $i<= @{$self->{probA}}+1; $i++) { # we implictely assume these are MEME-style frequencies x 10, so # 'a' represents the 'maximum', 10. Other positions can actually # add up to over 10 due to rounding, but I don't think that is a # problem? if (${$self->{probA}}[$i] and ${$self->{probA}}[$i] eq 'a') { ${$self->{probA}}[$i]='10'; } if (${$self->{probC}}[$i] and ${$self->{probC}}[$i] eq 'a') { ${$self->{probC}}[$i]='10'; } if (${$self->{probG}}[$i] and ${$self->{probG}}[$i] eq 'a') { ${$self->{probG}}[$i]='10'; } if (${$self->{probT}}[$i] and ${$self->{probT}}[$i] eq 'a') { ${$self->{probT}}[$i]='10'; } } } # Check for position with 0 for all bases, throw exception if so for (my $i=0;$i <= $#{$self->{probA}}; $i++) { if ((${$self->{probA}}[$i] + ${$self->{probC}}[$i] + ${$self->{probG}}[$i] + ${$self->{probT}}[$i]) == 0) { $self->throw("Position meaningless-all frequencies are 0"); } # apply psuedo-count correction to all values - this will result in # very bad frequencies if the input is already frequences and a # correction value as large as 1 is used! if ($self->{correction}) { ${$self->{probA}}[$i] += $self->{correction}; ${$self->{probC}}[$i] += $self->{correction}; ${$self->{probG}}[$i] += $self->{correction}; ${$self->{probT}}[$i] += $self->{correction}; } # (re)calculate frequencies my $div= ${$self->{probA}}[$i] + ${$self->{probC}}[$i] + ${$self->{probG}}[$i] + ${$self->{probT}}[$i]; ${$self->{probA}}[$i]=${$self->{probA}}[$i]/$div; ${$self->{probC}}[$i]=${$self->{probC}}[$i]/$div; ${$self->{probG}}[$i]=${$self->{probG}}[$i]/$div; ${$self->{probT}}[$i]=${$self->{probT}}[$i]/$div; } # Calculate the logs if ((!defined($self->{logA})) && ($input{model})) { $self->calc_weight($input{model}); } # Make consensus, throw if any one of the vectors is shorter $self->_calculate_consensus; return $self; } =head2 _calculate_consensus Title : _calculate_consensus Function: Internal stuff =cut sub _calculate_consensus { my $self=shift; my ($lc,$lt,$lg)=($#{$self->{probC}},$#{$self->{probT}},$#{$self->{probG}}); my $len=$#{$self->{probA}}; $self->throw("Probability matrix is damaged for C: $len vs $lc") if ($len != $lc); $self->throw("Probability matrix is damaged for T: $len vs $lt") if ($len != $lt); $self->throw("Probability matrix is damaged for G: $len vs $lg") if ($len != $lg); for (my $i=0; $i<$len+1; $i++) { #*** IUPACp values not actually used (eg. by next_pos) (${$self->{IUPAC}}[$i],${$self->{IUPACp}}[$i])=_to_IUPAC(${$self->{probA}}[$i], ${$self->{probC}}[$i], ${$self->{probG}}[$i], ${$self->{probT}}[$i]); (${$self->{seq}}[$i], ${$self->{seqp}}[$i]) = _to_cons(${$self->{probA}}[$i], ${$self->{probC}}[$i], ${$self->{probG}}[$i], ${$self->{probT}}[$i]); } return $self; } =head2 calc_weight Title : calc_weight Usage : $obj->calc_weight({A=>0.2562, C=>0.2438, G=>0.2432, T=>0.2568}); Function: Recalculates the PSM (or weights) based on the PFM (the frequency matrix) and user supplied background model. Throws : if no model is supplied Returns : n/a Args : reference to a hash with background frequencies for A,C,G and T =cut sub calc_weight { my ($self, $model) = @_; my %model; $model{probA}=$model->{A}; $model{probC}=$model->{C}; $model{probG}=$model->{G}; $model{probT}=$model->{T}; foreach my $let qw(probA probC probG probT) { my @str; $self->throw('You did not provide valid model\n') unless (($model{$let}>0) && ($model{$let}<1)); foreach my $f (@{$self->{$let}}) { my $w=log($f)-log($model{$let}); push @str,$w; } my $llet=$let; $llet=~s/prob/log/; $self->{$llet}=\@str; } return $self; } =head2 next_pos Title : next_pos Usage : Function: Retrives the next position features: frequencies for A,C,G,T, the main letter (as in consensus) and the probabilty for this letter to occur at this position and the current position Returns : hash (pA,pC,pG,pT,logA,logC,logG,logT,base,prob,rel) Args : none =cut sub next_pos { my $self = shift; $self->throw("instance method called on class") unless ref $self; my $len=@{$self->{seq}}; my $pos=$self->{_position}; # End reached? if ($pos<$len) { my $pA=${$self->{probA}}[$pos]; my $pC=${$self->{probC}}[$pos]; my $pG=${$self->{probG}}[$pos]; my $pT=${$self->{probT}}[$pos]; my $lA=${$self->{logA}}[$pos]; my $lC=${$self->{logC}}[$pos]; my $lG=${$self->{logG}}[$pos]; my $lT=${$self->{logT}}[$pos]; my $base=${$self->{seq}}[$pos]; my $prob=${$self->{seqp}}[$pos]; $self->{_position}++; my %seq=(pA=>$pA,pT=>$pT,pC=>$pC,pG=>$pG, lA=>$lA,lT=>$lT,lC=>$lC,lG=>$lG,base=>$base,rel=>$pos, prob=>$prob); return %seq; } else {$self->{_position}=0; return;} } =head2 curpos Title : curpos Usage : Function: Gets/sets the current position. Converts to 0 if argument is minus and to width if greater than width Returns : integer Args : integer =cut sub curpos { my $self = shift; my $prev = $self->{_position}; if (@_) { $self->{_position} = shift; } return $prev; } =head2 e_val Title : e_val Usage : Function: Gets/sets the e-value Returns : real number Args : none to get, real number to set =cut sub e_val { my $self = shift; my $prev = $self->{e_val}; if (@_) { $self->{e_val} = shift; } return $prev; } =head2 IC Title : IC Usage : Function: Get/set the Information Content Returns : real number Args : none to get, real number to set =cut sub IC { my $self = shift; my $prev = $self->{IC}; if (@_) { $self->{IC} = shift; } return $prev; } =head2 accession_number Title : accession_number Function: Get/set the accession number, this will be unique id for the SiteMatrix object as well for any other object, inheriting from SiteMatrix Returns : string Args : none to get, string to set =cut sub accession_number { my $self = shift; my $prev = $self->{accession_number}; if (@_) { $self->{accession_number} = shift; } return $prev; } =head2 consensus Title : consensus Usage : Function: Returns the consensus Returns : string Args : (optional) threshold value 1 to 10, default 5 '5' means the returned characters had a 50% or higher presence at their position =cut sub consensus { my ($self, $thresh) = @_; if ($thresh) { my $len=$#{$self->{probA}}; for (my $i=0; $i<$len+1; $i++) { (${$self->{seq}}[$i], ${$self->{seqp}}[$i]) = _to_cons(${$self->{probA}}[$i], ${$self->{probC}}[$i], ${$self->{probG}}[$i], ${$self->{probT}}[$i], $thresh); } } my $consensus=''; foreach my $letter (@{$self->{seq}}) { $consensus .= $letter; } return $consensus; } =head2 width Title : width Usage : Function: Returns the length of the sites in used to make this matrix Returns : int Args : none =cut sub width { my $self = shift; my $width=@{$self->{probA}}; return $width; } =head2 sites Title : sites Usage : Function: Get/set the number of sites that were used to make this matrix Returns : int Args : none to get, int to set =cut sub sites { my $self = shift; if (@_) { $self->{sites} = shift } return $self->{sites} || return; } =head2 IUPAC Title : IUPAC Usage : Function: Returns IUPAC compliant consensus Returns : string Args : optionally, also supply a whole number (int) of 1 or higher to set the significance level when considering the frequencies. 1 (the default) means a 0.05 significance level: frequencies lower than 0.05 will be ignored. 2 Means a 0.005 level, and so on. =cut sub IUPAC { my ($self, $thresh) = @_; if ($thresh) { my $len=$#{$self->{probA}}; for (my $i=0; $i<$len+1; $i++) { (${$self->{IUPAC}}[$i],${$self->{IUPACp}}[$i])=_to_IUPAC(${$self->{probA}}[$i], ${$self->{probC}}[$i], ${$self->{probG}}[$i], ${$self->{probT}}[$i], $thresh); } } my $iu=$self->{IUPAC}; my $iupac=''; foreach my $let (@{$iu}) { $iupac .= $let; } return $iupac; } =head2 _to_IUPAC Title : _to_IUPAC Usage : Function: Converts a single position to IUPAC compliant symbol. For rules see the implementation Returns : char, real number Args : real numbers for frequencies of A,C,G,T (positional) optionally, also supply a whole number (int) of 1 or higher to set the significance level when considering the frequencies. 1 (the default) means a 0.05 significance level: frequencies lower than 0.05 will be ignored. 2 Means a 0.005 level, and so on. =cut sub _to_IUPAC { my ($a, $c, $g, $t, $thresh) = @_; $thresh ||= 1; $thresh = int($thresh); $a = sprintf ("%.${thresh}f", $a); $c = sprintf ("%.${thresh}f", $c); $g = sprintf ("%.${thresh}f", $g); $t = sprintf ("%.${thresh}f", $t); my $total = $a + $c + $g + $t; return 'A' if ($a == $total); return 'G' if ($g == $total); return 'C' if ($c == $total); return 'T' if ($t == $total); my $r=$g+$a; return 'R' if ($r == $total); my $y=$t+$c; return 'Y' if ($y == $total); my $m=$a+$c; return 'M' if ($m == $total); my $k=$g+$t; return 'K' if ($k == $total); my $s=$g+$c; return 'S' if ($s == $total); my $w=$a+$t; return 'W' if ($w == $total); my $d=$r+$t; return 'D' if ($d == $total); my $v=$r+$c; return 'V' if ($v == $total); my $b=$y+$g; return 'B' if ($b == $total); my $h=$y+$a; return 'H' if ($h == $total); return 'N'; } =head2 _to_cons Title : _to_cons Usage : Function: Converts a single position to simple consensus character and returns its probability. For rules see the implementation Returns : char, real number Args : real numbers for A,C,G,T (positional), and optional 5th argument of threshold (as a number between 1 and 10, where 5 is default and means the returned character had a 50% or higher presence at this position) =cut sub _to_cons { my ($A, $C, $G, $T, $thresh) = @_; $thresh ||= 5; # this multiplication by 10 is just to satisfy the thresh range of 1-10 my $a = $A * 10; my $c = $C * 10; my $g = $G * 10; my $t = $T * 10; return 'N',10 if (($a<$thresh) && ($c<$thresh) && ($g<$thresh) && ($t<$thresh)); return 'N',10 if (($a==$t) && ($a==$c) && ($a==$g)); # threshold could be lower than 50%, so must check is not only over # threshold, but also the highest frequency return 'A',$a if (($a>=$thresh) && ($a>$t) && ($a>$c) && ($a>$g)); return 'C',$c if (($c>=$thresh) && ($c>$t) && ($c>$a) && ($c>$g)); return 'G',$g if (($g>=$thresh) && ($g>$t) && ($g>$c) && ($g>$a)); return 'T',$t if (($t>=$thresh) && ($t>$g) && ($t>$c) && ($t>$a)); return 'N',10; } =head2 get_string Title : get_string Usage : Function: Returns given probability vector as a string. Useful if you want to store things in a rel database, where arrays are not first choice Throws : If the argument is outside {A,C,G,T} Returns : string Args : character {A,C,G,T} =cut sub get_string { my $self=shift; my $base=shift; my $string=''; my @prob; BASE: { if ($base eq 'A') {@prob= @{$self->{probA}}; last BASE; } if ($base eq 'C') {@prob= @{$self->{probC}}; last BASE; } if ($base eq 'G') {@prob= @{$self->{probG}}; last BASE; } if ($base eq 'T') {@prob= @{$self->{probT}}; last BASE; } $self->throw ("No such base: $base!\n"); } foreach my $prob (@prob) { my $corrected = $prob*10; my $next=sprintf("%.0f",$corrected); $next='a' if ($next eq '10'); $string .= $next; } return $string; } =head2 get_array Title : get_array Usage : Function: Returns an array with frequencies for a specified base Returns : array Args : char =cut sub get_array { my $self=shift; my $base=uc(shift); return @{$self->{probA}} if ($base eq 'A'); return @{$self->{probC}} if ($base eq 'C'); return @{$self->{probG}} if ($base eq 'G'); return @{$self->{probT}} if ($base eq 'T'); $self->throw("No such base: $base!\n"); } =head2 get_logs_array Title : get_logs_array Usage : Function: Returns an array with log_odds for a specified base Returns : array Args : char =cut sub get_logs_array { my $self=shift; my $base=uc(shift); return @{$self->{logA}} if (($base eq 'A') && ($self->{logA})); return @{$self->{logC}} if (($base eq 'C') && ($self->{logC})); return @{$self->{logG}} if (($base eq 'G') && ($self->{logG})); return @{$self->{logT}} if (($base eq 'T') && ($self->{logT})); $self->throw ("No such base: $base!\n") if (!grep(/$base/,qw(A C G T))); return; } =head2 id Title : id Usage : Function: Gets/sets the site id Returns : string Args : string =cut sub id { my $self = shift; my $prev = $self->{id}; if (@_) { $self->{id} = shift; } return $prev; } =head2 regexp Title : regexp Usage : Function: Returns a regular expression which matches the IUPAC convention. N will match X, N, - and . Returns : string Args : none (works at the threshold last used for making the IUPAC string) =cut sub regexp { my $self=shift; my $regexp; foreach my $letter (@{$self->{IUPAC}}) { my $reg; LETTER: { if ($letter eq 'A') { $reg='[Aa]'; last LETTER; } if ($letter eq 'C') { $reg='[Cc]'; last LETTER; } if ($letter eq 'G') { $reg='[Gg]'; last LETTER; } if ($letter eq 'T') { $reg='[Tt]'; last LETTER; } if ($letter eq 'M') { $reg='[AaCcMm]'; last LETTER; } if ($letter eq 'R') { $reg='[AaGgRr]'; last LETTER; } if ($letter eq 'W') { $reg='[AaTtWw]'; last LETTER; } if ($letter eq 'S') { $reg='[CcGgSs]'; last LETTER; } if ($letter eq 'Y') { $reg='[CcTtYy]'; last LETTER; } if ($letter eq 'K') { $reg='[GgTtKk]'; last LETTER; } if ($letter eq 'V') { $reg='[AaCcGgVv]'; last LETTER; } if ($letter eq 'H') { $reg='[AaCcTtHh]'; last LETTER; } if ($letter eq 'D') { $reg='[AaGgTtDd]'; last LETTER; } if ($letter eq 'B') { $reg='[CcGgTtBb]'; last LETTER; } $reg='\S'; } $regexp .= $reg; } return $regexp; } =head2 regexp_array Title : regexp_array Usage : Function: Returns a regular expression which matches the IUPAC convention. N will match X, N, - and . Returns : array Args : none (works at the threshold last used for making the IUPAC string) To do : I have separated regexp and regexp_array, but maybe they can be rewritten as one - just check what should be returned =cut sub regexp_array { my $self=shift; my @regexp; foreach my $letter (@{$self->{IUPAC}}) { my $reg; LETTER: { if ($letter eq 'A') { $reg='[Aa]'; last LETTER; } if ($letter eq 'C') { $reg='[Cc]'; last LETTER; } if ($letter eq 'G') { $reg='[Gg]'; last LETTER; } if ($letter eq 'T') { $reg='[Tt]'; last LETTER; } if ($letter eq 'M') { $reg='[AaCcMm]'; last LETTER; } if ($letter eq 'R') { $reg='[AaGgRr]'; last LETTER; } if ($letter eq 'W') { $reg='[AaTtWw]'; last LETTER; } if ($letter eq 'S') { $reg='[CcGgSs]'; last LETTER; } if ($letter eq 'Y') { $reg='[CcTtYy]'; last LETTER; } if ($letter eq 'K') { $reg='[GgTtKk]'; last LETTER; } if ($letter eq 'V') { $reg='[AaCcGgVv]'; last LETTER; } if ($letter eq 'H') { $reg='[AaCcTtHh]'; last LETTER; } if ($letter eq 'D') { $reg='[AaGgTtDd]'; last LETTER; } if ($letter eq 'B') { $reg='[CcGgTtBb]'; last LETTER; } $reg='\S'; } push @regexp,$reg; } return @regexp; } =head2 _compress_array Title : _compress_array Usage : Function: Will compress an array of real signed numbers to a string (ie vector of bytes) -127 to +127 for bi-directional(signed) and 0..255 for unsigned Returns : String Args : array reference, followed by an max value and direction (optional, default 1-unsigned),1 unsigned, any other is signed. =cut sub _compress_array { my ($array,$lm,$direct)=@_; my $str; return unless(($array) && ($lm)); $direct=1 unless ($direct); my $k1= ($direct==1) ? (255/$lm) : (127/$lm); foreach my $c (@{$array}) { $c=$lm if ($c>$lm); $c=-$lm if (($c<-$lm) && ($direct !=1)); $c=0 if (($c<0) && ($direct ==1)); my $byte=int($k1*$c); $byte=127+$byte if ($direct !=1);#Clumsy, should be really shift the bits my $char=chr($byte); $str.=$char; } return $str; } =head2 _uncompress_string Title : _uncompress_string Usage : Function: Will uncompress a string (vector of bytes) to create an array of real signed numbers (opposite to_compress_array) Returns : string, followed by an max value and direction (optional, default 1-unsigned), 1 unsigned, any other is signed. Args : array =cut sub _uncompress_string { my ($str,$lm,$direct)=@_; my @array; return unless(($str) && ($lm)); $direct=1 unless ($direct); my $k1= ($direct==1) ? (255/$lm) : (127/$lm); foreach my $c (split(//,$str)) { my $byte=ord($c); $byte=$byte-127 if ($direct !=1);#Clumsy, should be really shift the bits my $num=$byte/$k1; push @array,$num; } return @array; } =head2 get_compressed_freq Title : get_compressed_freq Usage : Function: A method to provide a compressed frequency vector. It uses one byte to code the frequence for one of the probability vectors for one position. Useful for relational database. Improvment of the previous 0..a coding. Example : my $strA=$self->get_compressed_freq('A'); Returns : String Args : char =cut sub get_compressed_freq { my $self=shift; my $base=shift; my $string=''; my @prob; BASE: { if ($base eq 'A') { @prob= @{$self->{probA}} unless (!defined($self->{probA})); last BASE; } if ($base eq 'G') { @prob= @{$self->{probG}} unless (!defined($self->{probG})); last BASE; } if ($base eq 'C') { @prob= @{$self->{probC}} unless (!defined($self->{probC})); last BASE; } if ($base eq 'T') { @prob= @{$self->{probT}} unless (!defined($self->{probT})); last BASE; } $self->throw ("No such base: $base!\n"); } my $str= _compress_array(\@prob,1,1); return $str; } =head2 get_compressed_logs Title : get_compressed_logs Usage : Function: A method to provide a compressed log-odd vector. It uses one byte to code the log value for one of the log-odds vectors for one position. Example : my $strA=$self->get_compressed_logs('A'); Returns : String Args : char =cut sub get_compressed_logs { my $self=shift; my $base=shift; my $string=''; my @prob; BASE: { if ($base eq 'A') {@prob= @{$self->{logA}} unless (!defined($self->{logA})); last BASE; } if ($base eq 'C') {@prob= @{$self->{logC}} unless (!defined($self->{logC})); last BASE; } if ($base eq 'G') {@prob= @{$self->{logG}} unless (!defined($self->{logG})); last BASE; } if ($base eq 'T') {@prob= @{$self->{logT}} unless (!defined($self->{logT})); last BASE; } $self->throw ("No such base: $base!\n"); } return _compress_array(\@prob,1000,2); } =head2 sequence_match_weight Title : sequence_match_weight Usage : Function: This method will calculate the score of a match, based on the PWM if such is associated with the matrix object. Returns undef if no PWM data is available. Throws : if the length of the sequence is different from the matrix width Example : my $score=$matrix->sequence_match_weight('ACGGATAG'); Returns : Floating point Args : string =cut sub sequence_match_weight { my ($self,$seq)=@_; return unless ($self->{logA}); my $width=$self->width; $self->throw ("I can calculate the score only for sequence which are exactly my size for $seq, my width is $width\n") unless (length($seq)==@{$self->{logA}}); $seq = uc($seq); my @seq=split(//,$seq); my $score = 0; my $i=0; foreach my $pos (@seq) { my $tv = 'log'.$pos; $self->warn("Position ".($i+1)." of input sequence has unknown (ambiguity?) character '$pos': scores will be wrong") unless defined $self->{$tv}; $score += defined $self->{$tv} ? $self->{$tv}->[$i] : 0; $i++; } return $score; } =head2 get_all_vectors Title : get_all_vectors Usage : Function: returns all possible sequence vectors to satisfy the PFM under a given threshold Throws : If threshold outside of 0..1 (no sense to do that) Example : my @vectors=$self->get_all_vectors(4); Returns : Array of strings Args : (optional) floating =cut sub get_all_vectors { my $self=shift; my $thresh=shift; $self->throw("Out of range. Threshold should be >0 and 1<.\n") if (($thresh<0) || ($thresh>1)); my @seq=split(//,$self->consensus($thresh*10)); my @perm; for my $i (0..@{$self->{probA}}) { push @{$perm[$i]},'A' if ($self->{probA}->[$i]>$thresh); push @{$perm[$i]},'C' if ($self->{probC}->[$i]>$thresh); push @{$perm[$i]},'G' if ($self->{probG}->[$i]>$thresh); push @{$perm[$i]},'T' if ($self->{probT}->[$i]>$thresh); push @{$perm[$i]},'N' if ($seq[$i] eq 'N'); } my $fpos=shift @perm; my @strings=@$fpos; foreach my $pos (@perm) { my @newstr; foreach my $let (@$pos) { foreach my $string (@strings) { my $newstring = $string . $let; push @newstr,$newstring; } } @strings=@newstr; } return @strings; } 1;