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Bio::Align::DNAStatistics.3pm

NAME

Bio::Align::DNAStatistics - Calculate some statistics for a DNA alignment

SYNOPSIS

   use Bio::AlignIO;
   use Bio::Align::DNAStatistics;
 
 

   my $stats = new Bio::Align::DNAStatistics;
   my $alignin = new Bio::AlignIO(-format => 'emboss',
                                  -file   => 't/data/insulin.water');
   my $aln = $alignin->next_aln;
   my $jcmatrix = $stats->distance(-align => $aln, 
                                   -method => 'Jukes-Cantor');
 
 

   print $jcmatrix->print_matrix;
   ## and for measurements of synonymous /nonsynonymous substitutions ##
 
 

   my $in = new Bio::AlignIO(-format => 'fasta',
                             -file   => 't/data/nei_gojobori_test.aln');
   my $alnobj = $in->next_aln;
   my ($seq1id,$seq2id) = map { $_->display_id } $alnobj->each_seq;
   my $results = $stats->calc_KaKs_pair($alnobj, $seq1id, $seq2id);
   print "comparing ".$results->[0]{'Seq1'}." and ".$results->[0]{'Seq2'}."\n";
   for (sort keys %{$results->[0]} ){
       next if /Seq/;
       printf("%-9s %.4f \n",$_ , $results->[0]{$_});
   }
 
 

   my $results2 = $stats->calc_all_KaKs_pairs($alnobj);
   for my $an (@$results2){
       print "comparing ". $an->{'Seq1'}." and ". $an->{'Seq2'}. " \n";
       for (sort keys %$an ){
           next if /Seq/;
           printf("%-9s %.4f \n",$_ , $an->{$_});
       }
       print "\n\n";
   }
 
 

   my $result3 = $stats->calc_average_KaKs($alnobj, 1000);
   for (sort keys %$result3 ){
       next if /Seq/;
       printf("%-9s %.4f \n",$_ , $result3->{$_});
   }
 
 

DESCRIPTION

This object contains routines for calculating various statistics and distances for DNA alignments. The routines are not well tested and do contain errors at this point. Work is underway to correct them, but do not expect this code to give you the right answer currently! Use dnadist/distmat in the PHLYIP or EMBOSS packages to calculate the distances.

Several different distance method calculations are supported. Listed in brackets are the pattern which will match

JukesCantor [jc|jukes|jukescantor|jukes-cantor]

Uncorrected [jcuncor|uncorrected]

F81 [f81|felsenstein]

Kimura [k2|k2p|k80|kimura]

Tamura [t92|tamura|tamura92]

F84 [f84|felsenstein84]

TajimaNei [tajimanei|tajima\-nei]

JinNei [jinnei|jin\-nei] (not implemented)

There are also three methods to calculate the ratio of synonymous to non-synonymous mutations. All are implementations of the Nei-Gojobori evolutionary pathway method and use the Jukes-Cantor method of nucleotide substitution. This method works well so long as the nucleotide frequencies are roughly equal and there is no significant transition/transversion bias. In order to use these methods there are several pre-requisites for the alignment.

1

DNA alignment must be based on protein alignment. Use the subroutine aa_to_dna_aln in Bio::Align::Utilities to achieve this.

2

Therefore alignment gaps must be in multiples of 3 (representing an aa deletion/insertion) and at present must be indicated by a '-' symbol.

3

Alignment must be solely of coding region and be in reading frame 0 to achieve meaningful results

4

Alignment must therefore be a multiple of 3 nucleotides long.

5

All sequences must be the same length (including gaps). This should be the case anyway if the sequences have been automatically aligned using a program like Clustal.

6

Only the standard codon alphabet is supported at present.

calc_KaKs_pair() calculates a number of statistics for a named pair of sequences in the alignment.

calc_all_KaKs_pairs() calculates these statistics for all pairwise comparisons in an MSA. The statistics returned are:

S_d

Number of synonymous mutations between the 2 sequences.

N_d

Number of non-synonymous mutations between the 2 sequences.

S

Mean number of synonymous sites in both sequences.

N

mean number of synonymous sites in both sequences.

P_s

proportion of synonymous differences in both sequences given by P_s = S_d/S.

P_n

proportion of non-synonymous differences in both sequences given by P_n = S_n/S.

D_s

estimation of synonymous mutations per synonymous site (by Jukes-Cantor).

D_n

estimation of non-synonymous mutations per non-synonymous site (by Jukes-Cantor).

D_n_var

estimation of variance of D_n .

D_s_var

estimation of variance of S_n.

z_value

calculation of z value.Positive value indicates D_n > D_s, negative value indicates D_s > D_n.

The statistics returned by calc_average_KaKs are:

D_s

Average number of synonymous mutations/synonymous site.

D_n

Average number of non-synonymous mutations/non-synonymous site.

D_s_var

Estimated variance of Ds from bootstrapped alignments.

D_n_var

Estimated variance of Dn from bootstrapped alignments.

z_score

calculation of z value. Positive value indicates D_n >D_s, negative values vice versa.

The design of the code is based around the explanation of the Nei-Gojobori algorithm in the excellent book ``Molecular Evolution and Phylogenetics'' by Nei and Kumar, published by Oxford University Press. The methods have been tested using the worked example 4.1 in the book, and reproduce those results. If people like having this sort of analysis in BioPerl other methods for estimating Ds and Dn can be provided later.

Much of the DNA distance code is based on implementations in EMBOSS (Rice et al, www.emboss.org) [distmat.c] and PHYLIP (J. Felsenstein et al) [dnadist.c]. Insight also gained from Eddy, Durbin, Krogh, & Mitchison.

REFERENCES

D_JukesCantor

``Phylogenetic Inference'', Swoffrod, Olsen, Waddell and Hillis, in Mol. Systematics, 2nd ed, 1996, Ch 11. Derived from ``Evolution of Protein Molecules'', Jukes & Cantor, in Mammalian Prot. Metab., III, 1969, pp. 21-132.

D_Tamura

K Tamura, Mol. Biol. Evol. 1992, 9, 678.

D_Kimura

M Kimura, J. Mol. Evol., 1980, 16, 111.

JinNei

Jin and Nei, Mol. Biol. Evol. 82, 7, 1990.

D_TajimaNei

Tajima and Nei, Mol. Biol. Evol. 1984, 1, 269.

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
 
 

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:

   http://bugzilla.open-bio.org/
 
 

AUTHOR - Jason Stajich

Email jason-AT-bioperl.org

CONTRIBUTORS

Richard Adams, richard.adams@ed.ac.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 $obj = new Bio::Align::DNAStatistics();
  Function: Builds a new Bio::Align::DNAStatistics object 
  Returns : Bio::Align::DNAStatistics
  Args    : none
 
 

distance

  Title   : distance
  Usage   : my $distance_mat = $stats->distance(-align  => $aln, 
                                                -method => $method);
  Function: Calculates a distance matrix for all pairwise distances of
            sequences in an alignment.
  Returns : L<Bio::Matrix::PhylipDist> object
  Args    : -align  => Bio::Align::AlignI object
            -method => String specifying specific distance method 
                       (implementing class may assume a default)
 See also: L<Bio::Matrix::PhylipDist>
 
 

available_distance_methods

  Title   : available_distance_methods
  Usage   : my @methods = $stats->available_distance_methods();
  Function: Enumerates the possible distance methods
  Returns : Array of strings
  Args    : none
 
 

D - distance methods

D_JukesCantor

  Title   : D_JukesCantor
  Usage   : my $d = $stat->D_JukesCantor($aln)
  Function: Calculates D (pairwise distance) between 2 sequences in an 
            alignment using the Jukes-Cantor 1 parameter model. 
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
            double - gap penalty
 
 

D_F81

  Title   : D_F81
  Usage   : my $d = $stat->D_F81($aln)
  Function: Calculates D (pairwise distance) between 2 sequences in an 
            alignment using the Felsenstein 1981 distance model. 
            Relaxes the assumption of equal base frequencies that is
            in JC.
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
 
 

D_Uncorrected

  Title   : D_Uncorrected
  Usage   : my $d = $stats->D_Uncorrected($aln)
  Function: Calculate a distance D, no correction for multiple substitutions 
            is used.
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> (DNA Alignment)
            [optional] gap penalty
 
 

D_Kimura

  Title   : D_Kimura
  Usage   : my $d = $stat->D_Kimura($aln)
  Function: Calculates D (pairwise distance) between all pairs of sequences 
            in an alignment using the Kimura 2 parameter model.
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
 
 

D_Kimura_variance

  Title   : D_Kimura
  Usage   : my $d = $stat->D_Kimura_variance($aln)
  Function: Calculates D (pairwise distance) between all pairs of sequences 
            in an alignment using the Kimura 2 parameter model.
  Returns : array of 2 L<Bio::Matrix::PhylipDist>,
            the first is the Kimura distance and the second is
            a matrix of variance V(K)
  Args    : L<Bio::Align::AlignI> of DNA sequences
 
 

D_Tamura

  Title   : D_Tamura
  Usage   : Calculates D (pairwise distance) between 2 sequences in an 
            alignment using Tamura 1992 distance model. 
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
 
 

D_F84

  Title   : D_F84
  Usage   : my $d = $stat->D_F84($aln)
  Function: Calculates D (pairwise distance) between 2 sequences in an 
            alignment using the Felsenstein 1984 distance model. 
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
            [optional] double - gap penalty
 
 

D_TajimaNei

  Title   : D_TajimaNei
  Usage   : my $d = $stat->D_TajimaNei($aln)
  Function: Calculates D (pairwise distance) between 2 sequences in an 
            alignment using the TajimaNei 1984 distance model. 
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : Bio::Align::AlignI of DNA sequences
 
 

D_JinNei

  Title   : D_JinNei
  Usage   : my $d = $stat->D_JinNei($aln)
  Function: Calculates D (pairwise distance) between 2 sequences in an 
            alignment using the Jin-Nei 1990 distance model. 
  Returns : L<Bio::Matrix::PhylipDist>
  Args    : L<Bio::Align::AlignI> of DNA sequences
 
 

transversions

  Title   : transversions
  Usage   : my $transversions = $stats->transversion($aln);
  Function: Calculates the number of transversions between two sequences in 
            an alignment
  Returns : integer
  Args    : Bio::Align::AlignI
 
 

transitions

  Title   : transitions
  Usage   : my $transitions = Bio::Align::DNAStatistics->transitions($aln);
  Function: Calculates the number of transitions in a given DNA alignment
  Returns : integer representing the number of transitions
  Args    : Bio::Align::AlignI object
 
 

Data Methods

pairwise_stats

  Title   : pairwise_stats
  Usage   : $obj->pairwise_stats($newval)
  Function: 
  Returns : value of pairwise_stats
  Args    : newvalue (optional)
 
 

calc_KaKs_pair

  Title    : calc_KaKs_pair
  Useage   : my $results = $stats->calc_KaKs_pair($alnobj,
             $name1, $name2).
  Function : calculates Nei-Gojobori statistics for pairwise 
             comparison.
  Args     : A Bio::Align::AlignI compliant object such as a 
             Bio::SimpleAlign object, and 2 sequence name strings.
  Returns  : a reference to a hash of statistics with keys as 
             listed in Description.
 
 

calc_all_KaKs_pairs

  Title    : calc_all_KaKs_pairs
  Useage   : my $results2 = $stats->calc_KaKs_pair($alnobj).
  Function : Calculates Nei_gojobori statistics for all pairwise
             combinations in sequence.
  Arguments: A Bio::Align::ALignI compliant object such as
             a Bio::SimpleAlign object.
  Returns  : A reference to an array of hashes of statistics of
             all pairwise comparisons in the alignment.
 
 

calc_average_KaKs

  Title    : calc_average_KaKs.  
  Useage   : my $res= $stats->calc_average_KaKs($alnobj, 1000).
  Function : calculates Nei_Gojobori stats for average of all 
             sequences in the alignment.
  Args     : A Bio::Align::AlignI compliant object such as a
             Bio::SimpleAlign object, number of bootstrap iterations
             (default 1000).
  Returns  : A reference to a hash of statistics as listed in Description.
 
 

get_syn_changes

  Title   : get_syn_changes
  Usage   : Bio::Align::DNAStatitics->get_syn_chnages
  Function: Generate a hashref of all pairwise combinations of codns
            differing by 1
  Returns : Symetic matrix using hashes
            First key is codon
            and each codon points to a hashref of codons
            the values of which describe type of change.
            my $type = $hash{$codon1}->{$codon2};
            values are :
              1   synonymous
              0   non-syn
             -1   either codon is a stop codon
  Args    : none
 
 

dnds_pattern_number

  Title   : dnds_pattern_number
  Usage   : my $patterns = $stats->dnds_pattern_number($alnobj);
  Function: Counts the number of codons with no gaps in the MSA
  Returns : Number of codons with no gaps ('patterns' in PAML notation)
  Args    : A Bio::Align::AlignI compliant object such as a
             Bio::SimpleAlign object.