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";
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
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.
[email protected] - General discussion http://bioperl.org/wiki/Mailing_lists - About the mailing lists
Support
Please direct usage questions or support issues to the mailing list: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 [email protected]CONTRIBUTORS
Sendu Bala, [email protected]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
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.
_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: 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
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. Improvment 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