NAME

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

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 below
  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";

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 below):

  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

FEEDBACK

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

Support

Please direct usage questions or support issues to the mailing list:

bioperl-l@bioperl.org

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.

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:

  https://github.com/bioperl/bioperl-live/issues

AUTHOR - Stefan Kirov

Email skirov@utk.edu

CONTRIBUTORS

Sendu Bala, bix@sendu.me.uk

APPENDIX

The rest of the documentation details each of the object methods. Internal methods are usually preceded with a _

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
                           pseudo 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.

_calculate_consensus

 Title   : _calculate_consensus
 Function: Internal stuff

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

next_pos

 Title   : next_pos
 Usage   :
 Function: Retrieves 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

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

e_val

 Title   : e_val
 Usage   : 
 Function: Gets/sets the e-value
 Returns : real number
 Args    : none to get, real number to set

IC

 Title   : IC
 Usage   :
 Function: Get/set the Information Content
 Returns : real number
 Args    : none to get, real number to set

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

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

width

 Title   : width
 Usage   :
 Function: Returns the length of the sites in used to make this matrix
 Returns : int
 Args    : none

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

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.

_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.

_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)

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}

get_array

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

get_logs_array

 Title   : get_logs_array
 Usage   :
 Function: Returns an array with log_odds for a specified base
 Returns : array
 Args    : char

id

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

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)

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

_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.

_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

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. Improvement of the previous
           0..a coding.
 Example :  my $strA=$self->get_compressed_freq('A');
 Returns :  String
 Args    :  char

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

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

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