Summary

Bio::Matrix::PSM::SiteMatrix - SiteMatrixI implementation, holds a
position scoring matrix (or position weight matrix)

Package variables

Included modules

Inherit

Bio::Matrix::PSM::SiteMatrixI Bio::Root::Root

Synopsis

  use Bio::Matrix::PSM::SiteMatrix;
  # Create from memory by supplying probability matrix hash
  # both as strings or arrays
  # where $a,$c,$g and $t are either arrayref or string
  my ($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,
             -IC=>$ic,-e_val=>$score, -id=>$mid);
  my $site=new Bio::Matrix::PSM::SiteMatrix(%param);
  #Or get it from a file:
  use Bio::Matrix::PSM::IO;
  my $psmIO= new Bio::Matrix::PSM::IO(-file=>$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 highest probability or N if prob is too low
  my $consensus=$site->consensus;

  #Getting/using regular expression
  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";

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 frequencies where the frequency is {0..a} and a=1. This
is the way MEME 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 the constructor will check for positions that
equal 0. If such is found it will increase the count for all
positions by one and recalculate the frequency. Potential bug- if you
are using frequencies and one of the positions is 0 it will change
significantly. However, you should never have frequency that equals
0.
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.

Methods

Methods description

 Title   : new
 Usage   : my $site=new Bio::Matrix::PSM::SiteMatrix(-pA=>$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.
 Example :
 Returns :  Bio::Matrix::PSM::SiteMatrix object
 Args    :  hash

 Title   : _calculate_consensus
 Usage   :
 Function: Internal stuff
 Throws  :
 Example :
 Returns :
 Args    :

 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
 Throws  :
 Example :
 Returns : hash (pA,pC,pG,pT,base,prob,rel)
 Args    : none

 Title   : curpos
 Usage   :
 Function: Gets/sets the current position. Converts to 0 if argument is minus and
            to width if greater than width
 Throws  :
 Example :
 Returns : integer
 Args    : integer

 Title   : e_val
 Usage   :
 Function: Gets/sets the e-value
 Throws  :
 Example :
 Returns : real number
 Args    : real number

 Title   : IC
 Usage   :
 Function: Information content
 Throws  :
 Example :
 Returns : real number
 Args    : none

 Title   : accession_number
 Usage   :
 Function: accession number, this will be unique id for the SiteMatrix object as
 			well for any other object, inheriting from SiteMatrix
 Throws  :
 Example :
 Returns : string
 Args    : string

 Title   : consensus
 Usage   :
 Function: Returns the consensus
 Throws  :
 Example :
 Returns : string
 Args    :

 Title   : width
 Usage   :
 Function: Returns the length of the site
 Throws  :
 Example :
 Returns : number
 Args    :

 Title   : IUPAC
 Usage   :
 Function: Returns IUPAC compliant consensus
 Throws  :
 Example :
 Returns : string
 Args    :

 Title   : _to_IUPAC
 Usage   :
 Function: Converts a single position to IUPAC compliant symbol and returns its probability.
            For rules see the implementation
 Throws  :
 Example :
 Returns : char, real number
 Args    : real numbers for A,C,G,T (positional)

 Title   : _to_cons
 Usage   :
 Function: Converts a single position to simple consensus character and returns its probability.
            For rules see the implementation
 Throws  :
 Example :
 Returns : char, real number
 Args    : real numbers for A,C,G,T (positional)

 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}
 Example :
 Returns : string
 Args    : character {A,C,G,T}

 Title   : get_array
 Usage   :
 Function: Returns an array with frequencies for a specified base
 Throws  :
 Example :
 Returns : array
 Args    : char

 Title   : id
 Usage   :
 Function: Gets/sets the site id
 Throws  :
 Example :
 Returns : string
 Args    : string

 Title   : regexp
 Usage   :
 Function: Returns a regular expression which matches the IUPAC convention.
            N will match X, N, - and .
 Throws  :
 Example :
 Returns : string
 Args    :

 Title   : regexp_array
 Usage   :
 Function: Returns a regular expression which matches the IUPAC convention.
            N will match X, N, - and .
 Throws  :
 Example :
 Returns : array
 Args    :
 To do   : I have separated regexp and regexp_array, but
           maybe they can be rewritten as one - just check what should be returned

Methods code

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/-//gi; #deletes all dashes (only dashes)!
	$input{$key} = shift @args;
    }
    $self->{_position}   = 0;
    $self->{IC}     = $input{IC};
    $self->{e_val}  = $input{e_val};
    $self->{sites}  = $input{sites};
    $self->{width}  = $input{width};
    $self->{accession_number}=$input{accession_number};
    $self->{_correction}   =  defined($input{correction}) ? 
	$input{correction} : 1 ; # Correction might be unwanted- supply your own
    # No id provided, null for the sake of rel db
    $self->{id}= defined($input{id}) ? $input{id} : 'null'; 
	return $self unless (defined($input{pA}) && defined($input{pC}) && defined($input{pG}) && defined($input{pT}));
#Check for input type- no mixing alllowed, throw ex
    if (ref($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++) {
	    ${$self->{probA}}[$i]='10' if ( ${$self->{probA}}[$i] and ${$self->{probA}}[$i] eq 'a');
	    ${$self->{probC}}[$i]='10' if ( ${$self->{probC}}[$i] and ${$self->{probC}}[$i] eq 'a');
	    ${$self->{probG}}[$i]='10' if ( ${$self->{probG}}[$i] and ${$self->{probG}}[$i] eq 'a');
	    ${$self->{probT}}[$i]='10' if ( ${$self->{probT}}[$i] and ${$self->{probT}}[$i] eq 'a');
	}
#If this is MEME like output(probabilities, rather than count) here is the place for a check
    }
#Check for position with 0 for all bases, throw exception if so
#Correct 0 positions- inc by 1
    for (my $i=0;$i<$#{$self->{probA}}+1;$i++) {
	$self->throw("Position meaningless-all frequencies are 0") if ((${$self->{probA}}[$i]+${$self->{probC}}[$i]+${$self->{probG}}[$i]+${$self->{probT}}[$i])==0);
	$self->{_corrected}= ((${$self->{probA}}[$i]==0) || 
			      (${$self->{probG}}[$i]==0) || 
			      (${$self->{probC}}[$i]==0) || 
			      (${$self->{probT}}[$i]==0));
	if ($self->{_corrected}) {
	    ${$self->{probA}}[$i] += $self->{_correction};
	    ${$self->{probC}}[$i] += $self->{_correction};
	    ${$self->{probG}}[$i] += $self->{_correction};
	    ${$self->{probT}}[$i] += $self->{_correction};
	}
	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;
    }
#Make consensus, throw if any one of the vectors is shorter
    $self=_calculate_consensus($self);
    return $self;

}

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; $i++) {
	(${$self->{IUPAC}}[$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;

}

sub next_pos {

    my $self = shift;
    die "instance method called on class" unless ref $self;
    my $len=@{$self->{seq}};
    my $pos=$self->{_position};
    # End reached?
    if ($self->{_position}<$len) {
	my $pA=${$self->{probA}}[$pos];
	my $pC=${$self->{probC}}[$pos];
	my $pG=${$self->{probG}}[$pos];
	my $pT=${$self->{probT}}[$pos];
	my $base=${$self->{seq}}[$pos];
	my $prob=${$self->{seqp}}[$pos];
	$self->{_position}++;
	my %seq=(pA=>$pA,pT=>$pT,pC=>$pC,pG=>$pG, base=>$base,rel=>$pos, prob=>$prob);
	return %seq;
    }
    else {$self->{_position}=0; return undef;}

}

sub curpos {

    my $self = shift;
    my $prev = $self->{_position};
    if (@_) { $self->{_position} = shift; }
    return $prev;

}

sub e_val {

    my $self = shift;
    my $prev = $self->{e_val};
    if (@_) { $self->{e_val} = shift; }
    return $prev;

}

sub IC {

    my $self = shift;
    my $prev = $self->{IC};
    if (@_) { $self->{IC} = shift; }
    return $prev;

}

sub accession_number {

    my $self = shift;
    my $prev = $self->{accession_number};
    if (@_) { $self->{accession_number} = shift; }
    return $prev;

}

sub consensus {

  my $self = shift;
  my $consensus='';
  foreach my $letter (@{$self->{seq}}) {
     $consensus .= $letter;
  }
  return $consensus;

}

sub width {

  my $self = shift;
  my $width=@{$self->{probA}};
  return $width;

}

sub IUPAC {

	my $self = shift;
	my $iu=$self->{IUPAC};
	my $iupac='';
	foreach my $let (@{$iu}) {
		$iupac .= $let;
	}
return $iupac;

}

sub _to_IUPAC {

	my $A=shift;
	my $C=shift;
	my $G=shift;
	my $T=shift;
	my $all=$A+$G+$C+$T;
	my $a=$A/$all;
	my $g=$G/$all;
	my $c=$C/$all;
	my $t=$T/$all;
	my $single=0.7*$all;
	my $double=0.8*$all;
	my $triple=0.9*$all;
	return 'A',$a if ($a>$single);
	return 'G',$g if ($g>$single);
	return 'C',$c if ($c>$single);
	return 'T',$t if ($t>$single);
	my $r=$g+$a;
	return 'R',$r if ($r>$double);
	my $y=$t+$c;
	return 'Y',$y if ($y>$double);
	my $m=$a+$c;
	return 'M',$m if ($m>$double);
	my $k=$g+$t;
	return 'K',$k if ($k>$double);
	my $s=$g+$c;
	return 'S',$s if ($s>$double);
	my $w=$a+$t;
	return 'W',$w if ($w>$double);
	my $d=$r+$t;
	return 'D',$d if ($d>$triple);
	my $v=$r+$c;
	return 'V',$v if ($v>$triple);
	my $b=$y+$g;
	return 'B',$b if ($b>$triple);
	my $h=$y+$a;
	return 'H',$h if ($h>$triple);
	return 'N',0;

}

sub _to_cons {

	my $A=shift;
	my $C=shift;
	my $G=shift;
	my $T=shift;
	my $all=$A+$G+$C+$T;
	my $a=$A*10/$all;
	my $g=$G*10/$all;
	my $c=$C*10/$all;
	my $t=$T*10/$all;
	return 'A',$a if ($a>5);
	return 'G',$g if ($g>5);
	return 'C',$c if ($c>5);
	return 'T',$t if ($t>5);
	return 'N',10 if (($a==$t) && ($a==$c) && ($a==$g));
	return 'A',$a if (($a>$t) &&($a>$c) && ($a>$g));
	return 'C',$c if (($c>$t) &&($c>$a) && ($c>$g));
	return 'G',$g if (($g>$t) &&($g>$c) && ($g>$a));
	return 'N',10;

}

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;

}

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");

}

sub id {

    my $self = shift;
    my $prev = $self->{id};
    if (@_) { $self->{id} = shift; }
    return $prev;

}

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') { $reg='AaCc'; last LETTER; }
			if ($letter eq 'R') { $reg='AaGg'; last LETTER; }
			if ($letter eq 'W') { $reg='AaTt'; last LETTER; }
			if ($letter eq 'S') { $reg='CcGg'; last LETTER; }
			if ($letter eq 'Y') { $reg='CcTt'; last LETTER; }
			if ($letter eq 'K') { $reg='GgTt'; last LETTER; }
			if ($letter eq 'V') { $reg='AaCcGg'; last LETTER; }
			if ($letter eq 'H') { $reg='AaCcTt'; last LETTER; }
			if ($letter eq 'D') { $reg='AaGgTt'; last LETTER; }
			if ($letter eq 'B') { $reg='CcGgTt'; last LETTER; }
			if ($letter=~"AGCT-XN\.")  { $reg="\."; last LETTER; }
		}
		$regexp .= "[$reg]";
	}
return $regexp;

}

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') { $reg='AaCc'; last LETTER; }
			if ($letter eq 'R') { $reg='AaGg'; last LETTER; }
			if ($letter eq 'W') { $reg='AaTt'; last LETTER; }
			if ($letter eq 'S') { $reg='CcGg'; last LETTER; }
			if ($letter eq 'Y') { $reg='CcTt'; last LETTER; }
			if ($letter eq 'K') { $reg='GgTt'; last LETTER; }
			if ($letter eq 'V') { $reg='AaCcGg'; last LETTER; }
			if ($letter eq 'H') { $reg='AaCcTt'; last LETTER; }
			if ($letter eq 'D') { $reg='AaGgTt'; last LETTER; }
			if ($letter eq 'B') { $reg='CcGgTt'; last LETTER; }
			if ($letter=~"-XN\.")  { $reg="\."; last LETTER; }
		}
		push @regexp,$reg;
	}
return @regexp;

}

General documentation

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.

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the bugs and their resolution. Bug reports can be submitted via email
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Email skirov@utk.edu