Bio::PopGen::HtSNP(3pm) 				User Contributed Perl Documentation				   Bio::PopGen::HtSNP(3pm)

NAME

       Bio::PopGen::HtSNP.pm- Select htSNP from a haplotype set

SYNOPSIS

	   use Bio::PopGen::HtSNP;

	   my $obj = Bio::PopGen::HtSNP->new($hap,$snp,$pop);

DESCRIPTION

       Select the minimal set of SNP that contains the full information about the haplotype without redundancies.

       Take as input the followin values:

       - the haplotype block (array of array).
       - the snp id (array).
       - family information and frequency (array of array).

       The final haplotype is generated in a numerical format and the SNP's sets can be retrieve from the module.

       considerations:

       - If you force to include a family with indetermination, the SNP's with indetermination will be removed from the analysis, so consider
       before to place your data set what do you really want to do.

       - If two families have the same information (identical haplotype), one of them will be removed and the removed files will be stored
       classify as removed.

       - Only are accepted for calculation A, C, G, T and - (as deletion) and their combinations. Any other value as n or ? will be considered as
       degenerations due to lack of information.

   RATIONALE
       On a haplotype set is expected that some of the SNP and their variations contribute in the same way to the haplotype. Eliminating
       redundancies will produce a minimal set of SNP's that can be used as input for a taging selection process. On the process SNP's with the
       same variation are clustered on the same group.

       The idea is that because the tagging haplotype process is exponential. All redundant information we could eliminate on the tagging process
       will help to find a quick result.

   CONSTRUCTORS
	 my $obj = Bio::PopGen::HtSNP->new
	   (-haplotype_block => @haplotype_patterns,
	    -snp_ids	     => @snp_ids,
	    -pattern_freq    => @pattern_name_and_freq);

       where  $hap, $snp and $pop are in the format:

	 my $hap = [
		    'acgt',
		    'agtc',
		    'cgtc'
		   ];			  # haplotype patterns' id

	 my $snp = [qw/s1 s2 s3 s4/];	  # snps' Id's

	 my $pop = [
		    [qw/ uno	0.20/],
		    [qw/ dos	0.20/],
		    [qw/ tres	0.15/],
		   ];			  # haplotype_pattern_id    Frequency

   OBJECT METHODS
	   See Below for more detailed summaries.

DETAILS

   How the process is working with one example
       Let's begin with one general example of the code.

       Input haplotype:

	 acgtcca-t
	 cggtagtgc
	 cccccgtgc
	 cgctcgtgc

       The first thing to to is to split the haplotype into characters.

	 a	 c	 g	 t	 c	 c	 a	 -	 t
	 c	 g	 g	 t	 a	 g	 t	 g	 c
	 c	 c	 c	 c	 c	 g	 t	 g	 c
	 c	 g	 c	 t	 c	 g	 t	 g	 c

       Now we have to convert the haplotype to Upercase. This will produce the same SNP if we have input a or A.

	 A	 C	 G	 T	 C	 C	 A	 -	 T
	 C	 G	 G	 T	 A	 G	 T	 G	 C
	 C	 C	 C	 C	 C	 G	 T	 G	 C
	 C	 G	 C	 T	 C	 G	 T	 G	 C

       The program admit as values any combination of ACTG and - (deletions).  The haplotype is converted to number, considering the first
       variation as zero and the alternate value as 1 (see expanded description below).

	 0	 0	 0	 0	 0	 0	 0	 0	 0
	 1	 1	 0	 0	 1	 1	 1	 1	 1
	 1	 0	 1	 1	 0	 1	 1	 1	 1
	 1	 1	 1	 0	 0	 1	 1	 1	 1

       Once we have the haplotype converted to numbers we have to generate the snp type information for the haplotype.

       SNP code = SUM ( value * multiplicity ^ position );

	   where:
	     SUM is the sum of the values for the SNP
	     value is the SNP number code (0 [generally for the mayor allele],
					   1 [for the minor allele].
	     position is the position on the block.

       For this example the code is:

	 0	 0	 0	 0	 0	 0	 0	 0	 0
	 1	 1	 0	 0	 1	 1	 1	 1	 1
	 1	 0	 1	 1	 0	 1	 1	 1	 1
	 1	 1	 1	 0	 0	 1	 1	 1	 1
	------------------------------------------------------------------
	 14	 10	 12	 4	 2	 14	 14	 14	 14

	 14 = 0*2^0 + 1*2^1 + 1*2^2 + 1*2^3
	 12 = 0*2^0 + 1*2^1 + 0*2^2 + 1*2^3
	 ....

       Once we have the families classify. We will take just the SNP's not redundant.

	 14	 10	 12	 4	 2

       This information will be passed to the tag module is you want to tag the htSNP.

       Whatever it happens to one SNPs of a class will happen to a SNP of the same class. Therefore you don't need to scan redundancies

   Working with fuzzy data.
       This module is designed to work with fuzzy data. As the source of the haplotype is diverse. The program assume that some haplotypes can be
       generated using different values. If there is any indetermination (? or n) or any other degenerated value or invalid. The program will take
       away This SNP and will leave that for a further analysis.

       On a complex situation:

	 a	 c	 g	 t	 ?	 c	 a	 c	 t
	 a	 c	 g	 t	 ?	 c	 a	 -	 t
	 c	 g	 ?	 t	 a	 g	 ?	 g	 c
	 c	 a	 c	 t	 c	 g	 t	 g	 c
	 c	 g	 c	 t	 c	 g	 t	 g	 c
	 c	 g	 g	 t	 a	 g	 ?	 g	 c
	 a	 c	 ?	 t	 ?	 c	 a	 c	 t

       On this haplotype everything is happening. We have a multialelic variance.  We have indeterminations. We have deletions and we have even
       one SNP which is not a real SNP.

       The buiding process will be the same on this situation.

       Convert the haplotype to uppercase.

	 A	 C	 G	 T	 ?	 C	 A	 C	 T
	 A	 C	 G	 T	 ?	 C	 A	 -	 T
	 C	 G	 ?	 T	 A	 G	 ?	 G	 C
	 C	 A	 C	 T	 C	 G	 T	 G	 C
	 C	 G	 C	 T	 C	 G	 T	 G	 C
	 C	 G	 G	 T	 A	 G	 ?	 G	 C
	 A	 C	 ?	 T	 ?	 C	 A	 C	 T

       All columns that present indeterminations will be removed from the analysis on this Step.

       hapotype after remove columns:

	 A	 C	 T	 C	 C	 T
	 A	 C	 T	 C	 -	 T
	 C	 G	 T	 G	 G	 C
	 C	 A	 T	 G	 G	 C
	 C	 G	 T	 G	 G	 C
	 C	 G	 T	 G	 G	 C
	 A	 C	 T	 C	 C	 T

       All changes made on the haplotype matrix, will be also made on the SNP list.

	 snp_id_1 snp_id_2 snp_id_4 snp_id_6 snp_id_8 snp_id_9

       now the SNP that is not one SNP will be removed from the analysis.  SNP with Id snp_id_4 (the one with all T's).

       because of the removing. Some of the families will become the same and will be clustered. A posteriori analysis will diference these
       families.  but because of the indetermination can not be distinguish.

	 A	 C	 C	 C	 T
	 A	 C	 C	 -	 T
	 C	 G	 G	 G	 C
	 C	 A	 G	 G	 C
	 C	 G	 G	 G	 C
	 C	 G	 G	 G	 C
	 A	 C	 C	 C	 T

       The result of the mergering will go like:

	 A	 C	 C	 C	 T
	 A	 C	 C	 -	 T
	 C	 G	 G	 G	 C
	 C	 A	 G	 G	 C

       Once again the changes made on the families and we merge the frequency (to be implemented)

       Before to convert the haplotype into numbers we consider how many variations we have on the set. On this case the variations are 3.

       The control code will use on this situation base three as mutiplicity

	 0	 0	 0	 0	 0
	 0	 0	 0	 1	 0
	 1	 1	 1	 2	 1
	 1	 2	 1	 2	 1
	-----------------------------------
	 36	 63	 36	 75	 36

       And the minimal set for this combination is

	 0	 0	 0
	 0	 0	 1
	 1	 1	 2
	 1	 2	 2

       NOTE: this second example is a remote example an on normal conditions. This conditions makes no sense, but as the haplotypes, can come from
       many sources we have to be ready for all kind of combinations.

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 the
       Bioperl mailing list.  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 of the bugs and their resolution. Bug reports can be submitted via the
       web:

	 https://redmine.open-bio.org/projects/bioperl/

AUTHOR - Pedro M. Gomez-Fabre
       Email pgf18872-at-gsk-dot-com

APPENDIX

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

   new
	Title	: new
	Function: constructor of the class.
	Usage	: $obj-> Bio::PopGen::HtSNP->new(-haplotype_block
						 -snp_ids
						 -pattern_freq)
	Returns : self hash
	Args	: input haplotype (array of array)
		  snp_ids	  (array)
		  pop_freq	  (array of array)
	Status	: public

   haplotype_block
	Title	: haplotype_block
	Usage	: my $haplotype_block = $HtSNP->haplotype_block();
	Function: Get the haplotype block for a haplotype tagging selection
	Returns : reference of array
	Args	: reference of array with haplotype pattern

   snp_ids
	Title	: snp_ids
	Usage	: my $snp_ids = $HtSNP->$snp_ids();
	Function: Get the ids for a haplotype tagging selection
	Returns : reference of array
	Args	: reference of array with SNP ids

   pattern_freq
	Title	: pattern_freq
	Usage	: my $pattern_freq = $HtSNP->pattern_freq();
	Function: Get the pattern id and frequency  for a haplotype
		  tagging selection
	Returns : reference of array
	Args	: reference of array with SNP ids

   _check_input
	Title	: _check_input
	Usage	: _check_input($self)
	Function: check for errors on the input
	Returns : self hash
	Args	: self
	Status	: internal

   _haplotype_length_error
	Title	: _haplotype_length_error
	Usage	: _haplotype_length_error($self)
	Function: check if the haplotype length is the same that the one on the
		  SNP id list. If not break and exit
	Returns : self hash
	Args	: self
	Status	: internal

   _population_error
	Title	: _population_error
	Usage	: _population_error($self)
	Function: use input_block and pop_freq test if the number of elements
		  match. If doesn't break and quit.
	Returns : self hash
	Args	: self
	Status	: internal

   _do_it
	Title	: _do_it
	Usage	: _do_it($self)
	Function: Process the input generating the results.
	Returns : self hash
	Args	: self
	Status	: internal

   input_block
	Title	: input_block
	Usage	: $obj->input_block()
	Function: returns input block
	Returns : reference to array of array
	Args	: none
	Status	: public

   hap_length
	Title	: hap_length
	Usage	: $obj->hap_length()
	Function: get numbers of SNP on the haplotype
	Returns : scalar
	Args	: none
	Status	: public

   pop_freq
	Title	: pop_freq
	Usage	: $obj->pop_freq()
	Function: returns population frequency
	Returns : reference to array
	Args	: none
	Status	: public

   deg_snp
	Title	: deg_snp
	Usage	: $obj->deg_snp()
	Function: returns snp_removes due to indetermination on their values
	Returns : reference to array
	Args	: none
	Status	: public

   snp_type
	Title	: snp_type
	Usage	: $obj->snp_type()
	Function: returns hash with SNP type
	Returns : reference to hash
	Args	: none
	Status	: public

   silent_snp
	Title	: silent_snp
	Usage	: $obj->silent_snp()
	Function: some SNP's are silent (not contibuting to the haplotype)
		  and are not considering for this analysis
	Returns : reference to a array
	Args	: none
	Status	: public

   useful_snp
	Title	: useful_snp
	Usage	: $obj->useful_snp()
	Function: returns list of SNP's that are can be used as htSNP. Some
		  of them can produce the same information. But this is
		  not considered here.
	Returns : reference to a array
	Args	: none
	Status	: public

   ht_type
	Title	: ht_type
	Usage	: $obj->ht_type()
	Function: every useful SNP has a numeric code dependending of its
		  value and position. For a better description see
		  description of the module.
	Returns : reference to a array
	Args	: none
	Status	: public

   ht_set
	Title	: ht_set
	Usage	: $obj->ht_set()
	Function: returns the minimal haplotype in numerical format. This
		  haplotype contains the maximal information about the
		  haplotype variations but with no redundancies. It's the
		  minimal set that describes the haplotype.
	Returns : reference to an array of arrays
	Args	: none
	Status	: public

   snp_type_code
	Title	: snp_type_code
	Usage	: $obj->snp_type_code()
	Function: returns the numeric code of the SNPs that need to be
		  tagged that correspond to the SNP's considered in ht_set.
	Returns : reference to an array
	Args	: none
	Status	: public

   snp_and_code
	Title	: snp_and_code
	Usage	: $obj->snp_and_code()
	Function: Returns the full list of SNP's and the code associate to
		  them. If the SNP belongs to the group useful_snp it keep
		  this code. If the SNP is silent the code is 0. And if the
		  SNP is degenerated the code is -1.
	Returns : reference to an array of array
	Args	: none
	Status	: public

   deg_pattern
	Title	: deg_pattern
	Usage	: $obj->deg_pattern()
	Function: Returns the a list with the degenerated haplotype.
		  Sometimes due to degeneration some haplotypes looks
		  the same and if we don't remove them it won't find
		  any tag.
	Returns : reference to a hash of array
	Args	: none
	Status	: public

   split_hap
	Title	: split_hap
	Usage	: $obj->split_hap()
	Function: simple representation of the haplotype base by base
		  Same information that input haplotype but base based.
	Returns : reference to an array of array
	Args	: none
	Status	: public

   _split_haplo
	Title	: _split_haplo
	Usage	: _split_haplo($self)
	Function: Take a haplotype and split it into bases
	Returns : self
	Args	: none
	Status	: internal

   _to_upper_case
	Title	: _to_upper_case
	Usage	: _to_upper_case()
	Function: make SNP or in-dels Upper case
	Returns : self
	Args	: an AoA ref
	Status	: private

   _remove_deg
	Title	: _remove_deg
	Usage	: _remove_deg()
	Function: when have a indetermination or strange value this SNP
		  is removed
	Returns : haplotype family set and degeneration list
	Args	: ref to an AoA and a ref to an array
	Status	: internal

   _rem_silent_snp
	Title	: _rem_silent_snp
	Usage	: _rem_silent_snp()
	Function: there is the remote possibilty that one SNP won't be a
		  real SNP on this situation we have to remove this SNP,
		  otherwise the program won't find any tag
	Returns : nonthing
	Args	: ref to an AoA and a ref to an array
	Status	: internal

   _find_silent_snps
	Title	: _find_silent_snps
	Usage	:
	Function: list of snps that are not SNPs. All values for that
		  SNPs on the set is the same one. Look stupid but can
		  happend and if this happend you will not find any tag
	Returns : nothing
	Args	:
	Status	:

   _find_indet
	Title	: _find_indet
	Usage	:
	Function: find column (SNP) with invalid or degenerated values
		  and store this values into the second parameter supplied.
	Returns : nothing
	Args	: ref to AoA and ref to an array
	Status	: internal

   _remove_col
	Title	: _remove_col
	Usage	:
	Function: remove columns contained on the second array from
		  the first arr
	Returns : nothing
	Args	: array of array reference and array reference
	Status	: internal

   _remove_snp_id
	Title	: _remove_snp_id
	Usage	:
	Function: remove columns contained on the second array from
		  the first arr
	Returns : nothing
	Args	: array of array reference and array reference
	Status	: internal

   _find_deg_pattern
	Title	: _find_deg_pattern
	Usage	:
	Function: create a list with the degenerated patterns
	Returns : @array
	Args	: a ref to AoA
	Status	: public

   _keep_these_patterns
	Title	: _keep_these_patterns
	Usage	:
	Function: this is a basic approach, take a LoL and a list,
		  keep just the columns included on the list
	Returns : nothing
	Args	: an AoA and an array
	Status	: public

   compare_arrays
	Title	: compare_arrays
	Usage	:
	Function: take two arrays and compare their values
	Returns : 1 if the two values are the same
		  0 if the values are different
	Args	: an AoA and an array
	Status	: public

   _convert_to_numbers
	Title	: _convert_to_numbers
	Usage	: _convert_to_numbers()
	Function: tranform the haplotype into numbers. before to do that
		  we have to consider the variation on the set.
	Returns : nonthing
	Args	: ref to an AoA and a ref to an array
	Status	: internal

   _snp_type_code
	Title	: _snp_type_code
	Usage	:
	Function:
		  we have to create the snp type code for each version.
		  The way the snp type is created is the following:

		  we take the number value for every SNP and do the
		  following calculation

		  let be a SNP set as follow:

		  0    0
		  1    1
		  1    2

		  and multiplicity 3
		  on this case the situation is:

		  sum (value * multiplicity ^ position) for each SNP

		  0 * 3 ^ 0 + 1 * 3 ^ 1 + 1 * 3 ^ 2 = 12
		  0 * 3 ^ 0 + 1 * 3 ^ 1 + 2 * 3 ^ 2 = 21
	Returns : nothing
	Args	: $self
	Status	: private

   _alleles_number
	Title	: _alleles_number
	Usage	:
	Function: calculate the max number of alleles for a haplotype and
		  if the number. For each SNP the number is stored and the
		  max number of alleles for a SNP on the set is returned
	Returns : max number of alleles (a scalar storing a number)
	Args	: ref to AoA
	Status	: public

   _htSNP
	Title	: _htSNP
	Usage	: _htSNP()
	Function: calculate the minimal set that contains all information of the
		  haplotype.
	Returns : nonthing
	Args	: ref to an AoA and a ref to an array
	Status	: internal

   _snp_and_code_summary
	Title	: _snp_and_code_summary
	Usage	: _snp_and_code_summary()
	Function: compile on a list all SNP and the code for each. This
		  information can be also obtained combining snp_type and
		  snp_type_code but on these results the information about
		  the rest of SNP's are not compiled as table.

		  0 will be silent SNPs
		  -1 are degenerated SNPs
		  and the rest of positive values are the code for useful SNP

	Returns : nonthing
	Args	: ref to an AoA and a ref to an array
	Status	: internal

perl v5.14.2							    2012-03-02						   Bio::PopGen::HtSNP(3pm)