NAME

Bio::Tools::Run::Phylo::SLR - Wrapper around the SLR program

SYNOPSIS

  use Bio::Tools::Run::Phylo::SLR;
  use Bio::AlignIO;
  use Bio::TreeIO;
  use Bio::SimpleAlign;

  my $alignio = Bio::AlignIO->new
      (-format => 'fasta',
       -file   => 't/data/219877.cdna.fasta');

  my $aln = $alignio->next_aln;

  my $treeio = Bio::TreeIO->new
      (-format => 'newick', -file => 't/data/219877.tree');

  my $tree = $treeio->next_tree;

  my $slr = Bio::Tools::Run::Phylo::SLR->new();
  $slr->alignment($aln);
  $slr->tree($tree);
  # $rc = 1 for success, 0 for errors
  my ($rc,$results) = $slr->run();

  my $positive_sites = $results->{'positive'};

  print "# Site\tNeutral\tOptimal\tOmega\t",
        "lower\tupper\tLRT_Stat\tPval\tAdj.Pval\tResult\tNote\n";
  foreach my $positive_site (@$positive_sites) {
      print 
          $positive_site->[0], "\t",
          $positive_site->[1], "\t",
          $positive_site->[2], "\t",
          $positive_site->[3], "\t",
          $positive_site->[4], "\t",
          $positive_site->[5], "\t",
          $positive_site->[6], "\t",
          $positive_site->[7], "\t",
          $positive_site->[8], "\t",
          "positive\n";
  }

DESCRIPTION

This is a wrapper around the SLR program. See http://www.ebi.ac.uk/goldman/SLR/ for more information.

This module is more about generating the proper ctl file and will run the program in a separate temporary directory to avoid creating temp files all over the place.

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:

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

AUTHOR - Albert Vilella

Email avilella-at-gmail-dot-com

CONTRIBUTORS

Additional contributors names and emails here

APPENDIX

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

Default Values

INCOMPLETE DOCUMENTATION OF ALL METHODS

seqfile [incodon] File from which to read alignment of codon sequences. The file should be in PAML format.

treefile [intree] File from which tree should be read. The tree should be in Nexus format

outfile [slr.res] File to which results are written. If the file already exists, it will be overwritten.

reoptimise [1] Should the branch lengths, omega and kappa be reoptimized? 0 - no 1 - yes.

kappa [2.0] Value for kappa. If 'reoptimise' is specified, the value given will be used as am initial estimate,

omega [0.1] Value for omega (dN/dS). If 'reoptimise' is specified, the value given will be used as an initial estimate.

codonf [0] How codon frequencies are estimated: 0: F61/F60 Estimates used are the empirical frequencies from the data. 1: F3x4 The frequencies of nucleotides at each codon position are estimated from the data and then multiplied together to get the frequency of observing a given codon. The frequency of stop codons is set to zero, and all other frequencies scaled appropriately. 2: F1x4 Nucleotide frequencies are estimated from the data (not taking into account at which position in the codon it occurs). The nucleotide frequencies are multiplied together to get the frequency of observing and then corrected for stop codons.

freqtype [0] How codon frequencies are incorporated into the substitution matrix. 0: q_{ij} = pi_{j} s_{ij} 1: q_{ij} = \sqrt(pi_j/pi_i) s_{ij} 2: q_{ij} = \pi_{n} s_{ij}, where n is the nucleotide that the subsitution is to. 3: q_{ij} = s_{ij} / pi_i Option 0 is the tradition method of incorporating equilibrium frequencies into subsitution matrices (Felsenstein 1981; Goldman and Yang, 1994) Option 1 is described by Goldman and Whelan (2002), in this case with the additional parameter set to 0.5. Option 2 was suggested by Muse and Gaut (1994). Option 3 is included as an experiment, originally suggested by Bret Larget. it does not appear to describe evolution very successfully and should not be used for analyses.

  Kosakovsky-Pond has repeatedly stated that he finds incorporating codon
  frequencies in the manner of option 2 to be superior to option 0. We find
  that option 1 tends to perform better than either of these options.

positive_only [0] If only positively selected sites are of interest, set this to "1". Calculation will be slightly faster, but information about sites under purifying selection is lost.

gencode [universal] Which genetic code to use when determining whether a given mutation is synonymous or nonsynonymous. Currently only "universal" and "mammalian" mitochondrial are supported.

nucleof [0] Allow for empirical exchangabilities for nucleotide substitution. 0: No adjustment. All nucleotides treated the same, modulo transition / transversion. 1: The rate at which a substitution caused a mutation from nucleotide a to nucleotide b is adjust by a constant N_{ab}. This adjustment is in addition to other adjustments (e.g. transition / transversion or base frequencies).

aminof [0] Incorporate amino acid similarity parameters into substitution matrix, adjusting omega for a change between amino acid i and amino acid j. A_{ij} is a symmetric matrix of constants representing amino acid similarities. 0: Constant omega for all amino acid changes 1: omega_{ij} = omega^{A_{ij}} 2: omega_{ij} = a_{ij} log(omega) / [ 1 - exp(-a_{ij} log(omega)) ] Option 1 has the same form as the original codon subsitution model proposed by Goldman and Yang (but with potentially different constants). Option 2 has a more population genetic derivtion, with omega being interpreted as the ratio of fixation probabilities.

nucfile [nuc.dat] If nucleof is non-zero, read nucleotide substitution constants from nucfile. If this file does not exist, hard coded constants are used.

aminofile [amino.dat] If aminof is non-zero, read amino acid similarity constants from aminofile. If this file does not exist, hard coded constants are used.

timemem [0] Print summary of real time and CPU time used. Will eventually print summary of memory use as well.

ldiff [3.841459] Twice log-likelihood difference used as a threshold for calculating support (confidence) intervals for sitewise omega estimates. This value should be the quantile from a chi-square distribution with one degree of freedom corresponding to the support required. E.g. qchisq(0.95,1) = 3.841459 0.4549364 = 50% support 1.323304 = 75% support 2.705543 = 90% support 3.841459 = 95% support 6.634897 = 99% support 7.879439 = 99.5% support 10.82757 = 99.9% support

paramin [] If not blank, read in parameters from file given by the argument.

paramout [] If not blank, write out parameter estimates to file given.

skipsitewise [0] Skip sitewise estimation of omega. Depending on other options given, either calculate maximum likelihood or likelihood fixed at parameter values given.

seed [0] Seed for random number generator. If seed is 0, then previously produced seed file (~/.rng64) is used. If this does not exist, the random number generator is initialised using the clock.

saveseed [1] If non-zero, save finial seed in file (~/.rng64) to be used as initial seed in future runs of program.

Results Format

Results file (default: slr.res) ------------ Results are presented in nine columns

Site Number of sites in alignment

Neutral (minus) Log-probability of observing site given that it was evolving neutrally (omega=1)

Optimal (minus) Log-probability of observing site given that it was evolving at the optimal value of omega.

Omega The value of omega which maximizes the log-probability of observing

LRT_Stat Log-likelihood ratio statistic for non-neutral selection (or positive selection if the positive_only option is set to 1). LRT_Stat = 2 * (Neutral-Optimal)

Pval P-value for non-neutral (or positive) selection at a site, unadjusted for multiple comparisons.

Adj. Pval P-value for non-neutral (or positive) selection at a site, after adjusting for multiple comparisons using the Hochberg procedure (see the file "MultipleComparisons.txt" in the doc directory).

Result A simple visual guide to the result. Sites detected as having been under positive selection are marked with a '+', sites under purifying selection are marked with '-'. The number of symbols Number symbols Threshold 1 95% 2 99% 3 95% after adjustment 4 99% after adjustment

  Occasionally the result may also contain an exclamation mark. This
  indicates that the observation at a site is not significantly
  different from random (equivalent to infinitely strong positive
  selection). This may indicate that the alignment at that site is bad

Note

  The following events are flagged:
  Synonymous            All codons at a site code for the same amino 
                        acid.
  Single character      Only one sequence at the site is ungapped,
                        the result of a recent insertion for example.
  All gaps              All sequences at a site contain a gap
                        character.

  Sites marked "Single character" or "All gaps" are not counted
  towards the number of sites for the purposes of correcting for
  multiple comparisons since it is not possible to detect selection
  from none or one observation under the assumptions made by the
  sitewise likelihood ratio test.

program_name

 Title   : program_name
 Usage   : $factory->program_name()
 Function: holds the program name
 Returns:  string
 Args    : None

program_dir

 Title   : program_dir
 Usage   : ->program_dir()
 Function: returns the program directory, obtained from ENV variable.
 Returns:  string
 Args    :

new

 Title   : new
 Usage   : my $obj = Bio::Tools::Run::Phylo::SLR->new();
 Function: Builds a new Bio::Tools::Run::Phylo::SLR object 
 Returns : Bio::Tools::Run::Phylo::SLR
 Args    : -alignment => the Bio::Align::AlignI object
           -save_tempfiles => boolean to save the generated tempfiles and
                              NOT cleanup after onesself (default FALSE)
           -tree => the Bio::Tree::TreeI object
           -params => a hashref of SLR parameters (all passed to set_parameter)
           -executable => where the SLR executable resides

See also: Bio::Tree::TreeI, Bio::Align::AlignI

prepare

 Title   : prepare
 Usage   : my $rundir = $slr->prepare($aln);
 Function: prepare the SLR analysis using the default or updated parameters
           the alignment parameter must have been set
 Returns : value of rundir
 Args    : L<Bio::Align::AlignI> object,
           L<Bio::Tree::TreeI> object

run

 Title   : run
 Usage   : my ($rc,$parser) = $slr->run($aln,$tree);
 Function: run the SLR analysis using the default or updated parameters
           the alignment parameter must have been set
 Returns : Return code, L<Bio::Tools::Phylo::SLR>
 Args    : L<Bio::Align::AlignI> object,
           L<Bio::Tree::TreeI> object

error_string

 Title   : error_string
 Usage   : $obj->error_string($newval)
 Function: Where the output from the last analysus run is stored.
 Returns : value of error_string
 Args    : newvalue (optional)

alignment

 Title   : alignment
 Usage   : $slr->align($aln);
 Function: Get/Set the L<Bio::Align::AlignI> object
 Returns : L<Bio::Align::AlignI> object
 Args    : [optional] L<Bio::Align::AlignI>
 Comment : We could potentially add support for running directly on a file
           but we shall keep it simple
 See also: L<Bio::SimpleAlign>

tree

 Title   : tree
 Usage   : $slr->tree($tree, %params);
 Function: Get/Set the L<Bio::Tree::TreeI> object
 Returns : L<Bio::Tree::TreeI> 
 Args    : [optional] $tree => L<Bio::Tree::TreeI>,

 Comment : We could potentially add support for running directly on a file
           but we shall keep it simple
 See also: L<Bio::Tree::Tree>

get_parameters

 Title   : get_parameters
 Usage   : my %params = $self->get_parameters();
 Function: returns the list of parameters as a hash
 Returns : associative array keyed on parameter names
 Args    : none

set_parameter

 Title   : set_parameter
 Usage   : $slr->set_parameter($param,$val);
 Function: Sets a SLR parameter, will be validated against
           the valid values as set in the %VALIDVALUES class variable.  
           The checks can be ignored if one turns off param checks like this:
             $slr->no_param_checks(1)
 Returns : boolean if set was success, if verbose is set to -1
           then no warning will be reported
 Args    : $param => name of the parameter
           $value => value to set the parameter to
 See also: L<no_param_checks()>

set_default_parameters

 Title   : set_default_parameters
 Usage   : $slr->set_default_parameters(0);
 Function: (Re)set the default parameters from the defaults
           (the first value in each array in the 
            %VALIDVALUES class variable)
 Returns : none
 Args    : boolean: keep existing parameter values

Bio::Tools::Run::WrapperBase methods

no_param_checks

 Title   : no_param_checks
 Usage   : $obj->no_param_checks($newval)
 Function: Boolean flag as to whether or not we should
           trust the sanity checks for parameter values  
 Returns : value of no_param_checks
 Args    : newvalue (optional)

save_tempfiles

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

outfile_name

 Title   : outfile_name
 Usage   : my $outfile = $slr->outfile_name();
 Function: Get/Set the name of the output file for this run
           (if you wanted to do something special)
 Returns : string
 Args    : [optional] string to set value to

tempdir

 Title   : tempdir
 Usage   : my $tmpdir = $self->tempdir();
 Function: Retrieve a temporary directory name (which is created)
 Returns : string which is the name of the temporary directory
 Args    : none

cleanup

 Title   : cleanup
 Usage   : $slr->cleanup();
 Function: Will cleanup the tempdir directory after an SLR run
 Returns : none
 Args    : none

io

 Title   : io
 Usage   : $obj->io($newval)
 Function:  Gets a L<Bio::Root::IO> object
 Returns : L<Bio::Root::IO>
 Args    : none