package Bio::Graphics::Wiggle;
=head1 NAME
Bio::Graphics::Wiggle -- Binary storage for dense genomic features
=head1 SYNOPSIS
# all positions are 1-based
my $wig = Bio::Graphics::Wiggle->new('./test.wig',
$writeable,
{ seqid => $seqid,
start => $start,
step => $step,
min => $min,
max => $max });
$wig->erase;
my $seqid = $wig->seqid('new_id');
my $max = $wig->max($new_max);
my $min = $wig->min($new_min);
my $step = $wig->step($new_step); # data stored at modulus step == 0; all else is blank
$wig->set_value($position => $value); # store $value at position
$wig->set_values($position => \@values); # store array of values at position
$wig->set_range($start=>$end,$value); # store the same $value from $start to $end
my $value = $wig->value($position); # fetch value from position
my $values = $wig->values($start,$end); # fetch range of data from $start to $end
$wig->window(100); # sample window size
$wig->smoothing('mean'); # when sampling, compute the mean value across sample window
my $values = $wig->values($start,$end,$samples); # fetch $samples data points from $start to $end
=head1 DESCRIPTION
IMPORTANT NOTE: This implementation is still not right. See
http://genomewiki.ucsc.edu/index.php/Wiggle for a more space-efficient
implementation.
This module stores "wiggle" style quantitative genome data for display
in a genome browser application. The data for each chromosome (or
contig, or other reference sequence) is stored in a single file in the
following format:
256 byte header
50 bytes seqid, zero-terminated C string
4 byte long integer, value of "step" (explained later)
4 byte perl native float, the "min" value
4 byte perl native float, the "max" value
4 byte long integer, value of "span"
4 byte perl native float, the mean
4 byte perl native float, the standard deviation
2 byte unsigned short, the version number (currently version 0)
4 byte long integer, sequence start position (in 0-based coordinates)
null padding to 256 bytes for future use
The remainder of the file consists of 8-bit unsigned scaled integer
values. This means that all quantitative data will be scaled to 8-bit
precision!
For a convenient method of creating Wiggle files from UCSC-type WIG
input and creating GFF3 output, please see
L<Bio::Graphics::Wiggle::Loader>.
=head1 METHODS
=head2 Constructor and Accessors
=over 4
=item $wig = Bio::Graphics::Wiggle->new($filename,$writeable,{options})
Open/create a wiggle-format data file:
$filename -- path to the file to open/create
$writeable -- boolean value indicating whether file is
writeable. Missing files will only be created
if $writeable set to a true value. If path is
empty (undef or empty string) and writeable is true,
new() will create a temporary file that will be
deleted when the object goes out of scope.
{options} -- hash ref of the following named options, only valid
when creating a new wig file with $writeable true.
option name description default
----------- ----- -------
seqid name/id of sequence empty name
min minimum value of data points 0
max maximum value of data points 255
step interval between data points 1
span width of data points value of "step"
The "step" can be used to create sparse files to save space. By
default, step is set to 1, in which case a data value will be stored
at each base of the sequence. By setting step to 10, then each value
is taken to correspond to 10 bp, and the file will be 10x smaller.
For example, consider this step 5 data set:
1 2 3 4 5 6 7 8 9 10 11 12 13 14
20 . . . . 60 . . . . 80 . . .
We have stored the values "20" "60" and "80" at positions 1, 6 and 11,
respectively. When retrieving this data, it will appear as if
positions 1 through 5 have a value of 20, positions 6-10 have a value
of 60, and positions 11-14 have a value of 80. In the data file, we
store, positions 1,6,and 11 in adjacent bytes.
Note that no locking is performed by this module. If you wish to allow
multi-user write access to the databases files, you will need to
flock() the files yourself.
=item $seqid = $wig->seqid(['new_id'])
=item $max = $wig->max([$new_max])
=item $min = $wig->min([$new_min])
=item $step = $wig->step([$new_step])
=item $span = $wig->span([$new_span])
=item $mean = $wig->mean([$new_mean]);
=item $stdev = $wig->stdev([$new_stdev]);
These accessors get or set the corresponding values. Setting is only
allowed if the file was opened for writing. Note that changing the
min, max and step after writing data to the file under another
parameter set will produce unexpected (and invalid) results, as the
existing data is not automatically updated to be consistent.
=item $trim = $wig->trim([$new_trim]);
The trim method sets the trimming method, which can be used to trim
out extreme values. Three methods are currently supported:
none No trimming
stdev Trim 1 standard deviation above and below mean
stdevN Trim N standard deviations above and below the mean
In "stdevN", any can be any positive integer.
=back
=head2 Setting Data
=over 4
=item $wig->set_value($position => $value)
This method sets the value at $position to $value. If a step>1 is in
force, then $position will be rounded down to the nearest multiple of
step.
=item $wig->set_range($start=>$end, $value)
This method sets the value of all bases between $start and $end to
$value, honoring step.
=item $sig->set_values($position => \@values)
This method writes an array of values into the datababase beginning at
$position (or the nearest lower multiple of step). If step>1, then
values will be written at step intervals.
=back
=head2 Retrieving Data
=over 4
=item $value = $wig->value($position)
Retrieve the single data item at position $position, or the nearest
lower multiple of $step if step>1.
=item $values = $wig->values($start=>$end)
Retrieve the values in the range $start to $end and return them as an
array ref. Note that you will always get an array of size
($end-$start+1) even if step>1; the data in between the step intervals
will be filled in.
=item $values = $wig->values($start=>$end,$samples)
Retrieve a sampling of the values between $start and $end. Nothing
very sophisticated is done here; the code simply returns the number of
values indicated in $samples, smoothed according to the smoothing
method selected (default to "mean"), then selected at even intervals
from the range $start to $end. The return value is an arrayref of
exactly $samples values.
=item $string = $wig->export_to_wif($start,$end)
=item $string = $wig->export_to_wif64($start,$end)
Export the region from start to end in the "wif" format. This data can
later be imported into another Bio::Graphics::Wiggle object. The first
version returns a binary string. The second version returns a base64
encoded version that is safe for ascii-oriented formata such as GFF3
and XML.
=item $wig->import_from_wif($string)
=item $wig->import_from_wif64($string)
Import a wif format data string into the Bio::Graphics::Wiggle
object. The first version expects a binary string. The second version
expects a base64 encoded version that is safe for ascii-oriented
formata such as GFF3 and XML.
=back
=cut
# read/write genome tiling data, to be compatible with Jim Kent's WIG format
use strict;
use warnings;
use IO::File;
use Carp 'croak','carp','confess';
use constant HEADER_LEN => 256;
# seqid, step, min, max, span, mean, stdev, version, start
use constant HEADER => '(Z50LFFLFFSL)@'.HEADER_LEN;
use constant BODY => 'C';
use constant DEBUG => 0;
use constant DEFAULT_SMOOTHING => 'mean';
use constant VERSION => 0;
our $VERSION = '1.0';
sub new {
my $class = shift;
my ($path,$write,$options) = @_;
$path ||= ''; # to avoid uninit warning
my $mode = $write ? -e $path # if file already exists...
? '+<' # ...open for read/write
: '+>' # ...else clobber and open a new one
: '<'; # read only
my $fh = $class->new_fh($path,$mode);
$fh or die (($path||'temporary file').": $!");
$options ||= {};
my $self = bless {fh => $fh,
write => $write,
dirty => scalar keys %$options
}, ref $class || $class;
my $stored_options = eval {$self->_readoptions} || {};
$options->{start}-- if defined $options->{start}; # 1-based ==> 0-based coordinates
my %merged_options = (%$stored_options,%$options);
# warn "merged options = ",join ' ',%merged_options;
$merged_options{version}||= 0;
$merged_options{seqid} ||= 'chrUnknown';
$merged_options{min} ||= 0;
$merged_options{max} ||= 255;
$merged_options{mean} ||= 128;
$merged_options{stdev} ||= 255;
$merged_options{trim} ||= 'none';
$merged_options{step} ||= 1;
$merged_options{start} ||= 0;
$merged_options{span} ||= $merged_options{step};
$self->{options} = \%merged_options;
$self->_do_trim unless $self->trim eq 'none';
return $self;
}
sub new_fh {
my $self = shift;
my ($path,$mode) = @_;
return $path ? IO::File->new($path,$mode)
: IO::File->new_tmpfile;
}
sub end {
my $self = shift;
unless (defined $self->{end}) {
my $size = (stat($self->fh))[7];
my $data_len = $size - HEADER_LEN();
return unless $data_len>0; # undef end
$self->{end} = ($self->start-1) + $data_len * $self->step;
}
return $self->{end};
}
sub DESTROY { shift->write }
sub erase {
my $self = shift;
$self->fh->truncate(HEADER_LEN);
}
sub fh { shift->{fh} }
sub seek { shift->fh->seek(shift,0) }
sub tell { shift->fh->tell() }
sub _option {
my $self = shift;
my $option = shift;
my $d = $self->{options}{$option};
if (@_) {
$self->{dirty}++;
$self->{options}{$option} = shift;
delete $self->{scale} if $option eq 'min' or $option eq 'max';
}
return $d;
}
sub version { shift->_option('version',@_) }
sub seqid { shift->_option('seqid',@_) }
sub min { shift->_option('min',@_) }
sub max { shift->_option('max',@_) }
sub step { shift->_option('step',@_) }
sub span { shift->_option('span',@_) }
sub mean { shift->_option('mean',@_) }
sub stdev { shift->_option('stdev',@_) }
sub trim { shift->_option('trim',@_) }
sub start { # slightly different because we have to deal with 1 vs 0-based coordinates
my $self = shift;
my $start = $self->_option('start');
$start++; # convert into 1-based coordinates
if (@_) {
my $newstart = shift;
$self->_option('start',$newstart-1); # store in zero-based coordinates
}
return $start;
}
sub smoothing {
my $self = shift;
my $d = $self->{smoothing} || DEFAULT_SMOOTHING;
$self->{smoothing} = shift if @_;
$d;
}
sub write {
my $self = shift;
if ($self->{dirty} && $self->{write}) {
$self->_writeoptions($self->{options});
undef $self->{dirty};
$self->fh->flush;
}
}
sub _readoptions {
my $self = shift;
my $fh = $self->fh;
my $header;
$fh->seek(0,0);
return unless $fh->read($header,HEADER_LEN) == HEADER_LEN;
return $self->_parse_header($header);
}
sub _parse_header {
my $self = shift;
my $header = shift;
my ($seqid,$step,$min,$max,$span,
$mean,$stdev,$version,$start) = unpack(HEADER,$header);
return { seqid => $seqid,
step => $step,
span => $span,
min => $min,
max => $max,
mean => $mean,
stdev => $stdev,
version => $version,
start => $start,
};
}
sub _generate_header {
my $self = shift;
my $options = shift;
return pack(HEADER,@{$options}{qw(seqid step min max span mean stdev version start)});
}
sub _writeoptions {
my $self = shift;
my $options = shift;
my $fh = $self->fh;
my $header = $self->_generate_header($options);
$fh->seek(0,0);
$fh->print($header) or die "write failed: $!";
}
sub _do_trim {
my $self = shift;
# don't trim if there is no score range
($self->max - $self->min) or return;
my $trim = lc $self->trim;
my ($method,$arg);
if ($trim =~ /([a-z]+)(\d+)/) {
$method = "_trim_${1}";
$arg = $2;
}
else {
$method = "_trim_${trim}";
}
unless ($self->can($method)) {
carp "invalid trim method $trim";
return;
}
$self->$method($arg);
}
# trim n standard deviations from the mean
sub _trim_stdev {
my $self = shift;
my $factor = shift || 1;
my $mean = $self->mean;
my $stdev = $self->stdev * $factor;
my $min = $self->min > $mean - $stdev ? $self->min : $mean - $stdev;
my $max = $self->max < $mean + $stdev ? $self->max : $mean + $stdev;
warn "_trim_stdev (* $factor) : setting min to $min, max to $max (was ",$self->min,',',$self->max,')'
if DEBUG;
$self->min($min);
$self->max($max);
}
sub set_value {
my $self = shift;
croak "usage: \$wig->set_value(\$position => \$value)"
unless @_ == 2;
$self->value(@_);
}
sub set_range {
my $self = shift;
croak "usage: \$wig->set_range(\$start_position => \$end_position, \$value)"
unless @_ == 3;
$self->value(@_);
}
sub value {
my $self = shift;
my $position = shift;
my $offset = $self->_calculate_offset($position);
$offset >= HEADER_LEN or die "Tried to retrieve data from before start position";
$self->seek($offset) or die "Seek failed: $!";
if (@_ == 2) {
my $end = shift;
my $new_value = shift;
my $step = $self->step;
my $scaled_value = $self->scale($new_value);
$self->fh->print(pack('C*',($scaled_value)x(($end-$position+1)/$step))) or die "Write failed: $!";
$self->{end} = $end if !exists $self->{end} || $self->{end} < $end;
}
elsif (@_==1) {
my $new_value = shift;
my $scaled_value = $self->scale($new_value);
$self->fh->print(pack('C*',$scaled_value)) or die "Write failed: $!";
$self->{end} = $position if !exists $self->{end} || $self->{end} < $position;
return $new_value;
}
else { # retrieving data
my $buffer;
$self->fh->read($buffer,1) or die "Read failed: $!";
my $scaled_value = unpack('C*',$buffer);
# missing data, so look back at most span values to get it
if ($scaled_value == 0 && (my $span = $self->span) > 1) {
$offset = $self->_calculate_offset($position-$span+1);
$offset >= HEADER_LEN or die "Tried to retrieve data from before start position";
$self->seek($offset) or die "Seek failed: $!";
$self->fh->read($buffer,$span/$self->step);
for (my $i=length($buffer)-2;$i>=0;$i--) {
my $val = substr($buffer,$i,1);
next if $val eq "\0";
$scaled_value = unpack('C*',$val);
last;
}
}
return $self->unscale($scaled_value);
}
}
sub _calculate_offset {
my $self = shift;
my $position = shift;
my $step = $self->step;
my $start = $self->start;
return HEADER_LEN + int(($position-$start)/$step);
}
sub set_values {
my $self = shift;
croak "usage: \$wig->set_values(\$position => \@values)"
unless @_ == 2 and ref $_[1] eq 'ARRAY';
$self->values(@_);
}
# read or write a series of values
sub values {
my $self = shift;
my $start = shift;
if (ref $_[0] && ref $_[0] eq 'ARRAY') {
$self->_store_values($start,@_);
} else {
$self->_retrieve_values($start,@_);
}
}
sub export_to_wif64 {
my $self = shift;
my $data = $self->export_to_wif(@_);
eval "require MIME::Base64"
unless MIME::Base64->can('encode_base64');
return MIME::Base64::encode_base64($data);
}
sub import_from_wif64 {
my $self = shift;
my $data = shift;
eval "require MIME::Base64"
unless MIME::Base64->can('decode_base64');
return $self->import_from_wif(MIME::Base64::decode_base64($data));
}
# subregion in "wiggle interchange format" (wif)
sub export_to_wif {
my $self = shift;
my ($start,$end) = @_;
# get the 256 byte header
my $data = $self->_generate_header($self->{options});
# add the range to the data (8 bytes overhead)
$data .= pack("L",$start);
$data .= pack("L",$end);
# add the packed data for this range
$data .= $self->_retrieve_packed_range($start,$end-$start+1,$self->step);
return $data;
}
sub export_to_bedgraph {
my $self = shift;
my ($start,$end,$fh) = @_;
my $max_range = 100_000;
$start ||= 1;
$end ||= $self->end;
my $lines;
for (my $s=$start;$s<$end;$s+=$max_range) {
my $e = $s + $max_range - 1;
$e = $end if $e > $end;
my $b = $self->values($s,$e);
$lines .= $self->_bedgraph_lines($s,$b,$fh);
}
return $lines;
}
sub _bedgraph_lines {
my $self = shift;
my ($start,$values,$fh) = @_;
my $seqid = $self->seqid;
my $result;
my ($last_val,$last_start,$end);
$last_start = $start-1; # 0 based indexing
for (my $i=0;$i<@$values;$i++) {
my $v = $values->[$i];
if (!defined $v) {
if (defined $last_val) {
$result .= $self->_append_or_print_bedgraph($fh,$seqid,$last_start,$start+$i-1,$last_val);
undef $last_val;
}
$last_start = $start+$i;
next;
}
if (defined $last_val && $last_val != $v) {
$result .= $self->_append_or_print_bedgraph($fh,$seqid,$last_start,$start+$i-1,$last_val);
$last_start = $start+$i-1;
}
$last_val = $v;
$end = $start+$i-1;
}
$result .= $self->_append_or_print_bedgraph($fh,$seqid,$last_start,$end+1,$last_val) if $last_val;
return $result;
}
sub _append_or_print_bedgraph {
my $self = shift;
my ($fh,$seqid,$start,$end,$val) = @_;
my $data = join("\t",$seqid,$start,$end,sprintf("%.2f",$val))."\n";
if ($fh) {
print $fh $data;
return '';
} else {
return $data;
}
}
sub import_from_wif {
my $self = shift;
my $wifdata = shift;
# BUG: should check that header is compatible
my $header = substr($wifdata,0,HEADER_LEN);
my $start = unpack('L',substr($wifdata,HEADER_LEN, 4));
my $end = unpack('L',substr($wifdata,HEADER_LEN+4,4));
my $options = $self->_parse_header($header);
my $stored_options = eval {$self->_readoptions} || {};
my %merged_options = (%$stored_options,%$options);
$self->{options} = \%merged_options;
$self->{dirty}++;
# write the data
$self->seek($self->_calculate_offset($start));
$self->fh->print(substr($wifdata,HEADER_LEN+8)) or die "write failed: $!";
$self->{end} = $end if !defined $self->{end} or $self->{end} < $end;
}
sub _retrieve_values {
my $self = shift;
my ($start,$end,$samples) = @_;
my $data_start = $self->start;
my $step = $self->step;
my $span = $self->span;
croak "Value of start position ($start) is less than data start of $data_start"
unless $start >= $data_start;
croak "Value of end position ($end) is greater than data end of ",$self->end+$span,
unless $end <= $self->end + $span;
# generate list of positions to sample from
my $length = $end-$start+1;
$samples ||= $length;
# warn "samples = $samples, length=$length, span=$span, step=$step";
# if the length is grossly greater than the samples, then we won't even
# bother fetching all the data, but just sample into the disk file
if ($length/$samples > 100 && $step == 1) {
my @result;
# my $window = 20*($span/$step);
my $interval = $length/$samples;
# my $window = 100*$interval/$span;
my $window = $interval/2;
# warn "window = $window, interval = $interval";
for (my $i=0;$i<$samples;$i++) {
my $packed_data = $self->_retrieve_packed_range(int($start+$i*$interval-$window),
int($window),
$step);
my @bases= grep {$_} unpack('C*',$packed_data);
if (@bases) {
local $^W = 0;
my $arry = $self->unscale(\@bases);
my $n = @$arry;
my $total = 0;
$total += $_ foreach @$arry;
my $mean = $total/$n;
my $max;
for (@$arry) { $max = $_ if !defined $max || $max < $_ }
# warn $start+$i*$interval,': ',join(',',map {int($_)} @$arry),
# " mean = $mean, max = $max";
# push @result,$mean;
push @result,$max;
} else {
push @result,0;
}
}
return \@result;
}
my $packed_data = $self->_retrieve_packed_range($start,$length,$step);
my @bases;
$#bases = $length-1;
if ($step == $span) {
# in this case, we do not have any partially-empty
# steps, so can operate on the step-length data structure
# directly
@bases = unpack('C*',$packed_data);
}
else {
# In this case some regions may have partially missing data,
# so we create an array equal to the length of the requested region,
# fill it in, and then sample it
for (my $i=0; $i<length $packed_data; $i++) {
my $index = $i * $step;
my $value = unpack('C',substr($packed_data,$i,1));
next unless $value; # ignore 0 values
@bases[$index..$index+$span-1] = ($value) x $span;
}
$#bases = $length-1;
}
my $r = $self->unscale(\@bases);
$r = $self->sample($r,$samples);
$r = $self->smooth($r,$self->window * $samples/@bases)
if defined $self->window && $self->window>1;
return $r;
}
sub _retrieve_packed_range {
my $self = shift;
my ($start,$length,$step) = @_;
my $span = $self->span;
my $offset = $self->_calculate_offset($start);
$self->seek($offset);
my $packed_data;
$self->fh->read($packed_data,$length/$step);
# pad data up to required amount
$packed_data .= "\0" x ($length/$step-length($packed_data))
if length $packed_data < $length/$step;
return $packed_data;
}
sub sample {
my $self = shift;
my ($values,$samples) = @_;
my $length = @$values;
my $window_size = $length/$samples;
my @samples;
$#samples = $samples-1;
if ($window_size < 2) { # no data smoothing needed
@samples = map { $values->[$_*$window_size] } (0..$samples-1);
}
else {
my $smoothsub = $self->smoothsub;
for (my $i=0; $i<$samples; $i++) {
my $start = $i * $window_size;
my $end = $start + $window_size - 1;
my @window = @{$values}[$start..$end];
my $value = $smoothsub->(\@window);
$samples[$i] = $value;
}
}
return \@samples;
}
sub smoothsub {
my $self = shift;
my $smoothing = $self->smoothing;
my $smoothsub = $smoothing eq 'mean' ? \&sample_mean
:$smoothing eq 'max' ? \&sample_max
:$smoothing eq 'min' ? \&sample_min
:$smoothing eq 'none' ? \&sample_center
:croak("invalid smoothing type '$smoothing'");
return $smoothsub;
}
sub smooth {
my ($self,$data,$window) = @_;
my $smoothing = $self->smoothing;
$window ||= $self->window;
return $data if $smoothing eq 'none' || $window < 2;
my @data = @$data;
my $smoother = $self->smoothsub;
$window++ unless $window % 2;
my $offset = int($window/2);
for (my $i=$offset; $i<@$data-$offset; $i++) {
my $start = $i - $offset;
my $end = $i + $offset;
my @subset = @data[$start..$end];
$data->[$i] = $smoother->(\@subset);
}
return $data;
}
sub window {
my $self = shift;
my $d = $self->{window};
$self->{window} = shift if @_;
$d;
}
sub sample_mean {
my $values = shift;
my ($total,$items);
for my $v (@$values) {
next unless defined $v;
$items++;
$total+=$v;
}
return $items ? $total/$items : undef;
}
sub sample_max {
my $values = shift;
my $max;
for my $v (@$values) {
next unless defined $v;
$max = $v if !defined $max or $max < $v;
}
return $max;
}
sub sample_min {
my $values = shift;
my $min;
for my $v (@$values) {
next unless defined $v;
$min = $v if !defined $min or $min > $v;
}
return $min;
}
sub sample_center {
my $values = shift;
return $values->[@$values/2];
}
sub _store_values {
my $self = shift;
my ($position,$data) = @_;
# where does data start
my $offset = $self->_calculate_offset($position);
my $fh = $self->fh;
my $step = $self->step;
my $scaled = $self->scale($data);
$self->seek($offset);
my $packed_data = pack('C*',@$scaled);
$fh->print($packed_data) or die "Write failed: $!";
my $new_end = $position+@$data-1;
$self->{end} = $new_end if !exists $self->{end} || $self->{end} < $new_end;
}
# zero means "no data"
# everything else is scaled from 1-255
sub scale {
my $self = shift;
my $values = shift;
my $scale = $self->_get_scale;
my $min = $self->{options}{min};
if (ref $values && ref $values eq 'ARRAY') {
my @return = map {
my $i = ($_ - $min)/$scale;
my $v = 1 + int($i+0.5*($i<=>0)); # avoid call to round()
$v = 1 if $v < 1;
$v = 255 if $v > 255;
$v;
} @$values;
return \@return;
} else {
my $v = 1 + round (($values - $min)/$scale);
$v = 1 if $v < 1;
$v = 255 if $v > 255;
return $v;
}
}
sub unscale {
my $self = shift;
my $values = shift;
my $scale = $self->_get_scale;
my $min = $self->{options}{min};
if (ref $values && ref $values eq 'ARRAY') {
my @return = map {$_ ? (($_-1) * $scale + $min) : undef} @$values;
return \@return;
} else {
return $values ? ($values-1) * $scale + $min : undef;
}
}
sub _get_scale {
my $self = shift;
unless ($self->{scale}) {
my $min = $self->{options}{min};
my $max = $self->{options}{max};
my $range = $max - $min || 0.001; # can't be zero!
$self->{scale} = $range/254;
}
return $self->{scale};
}
sub round {
return int($_[0]+0.5*($_[0]<=>0));
}
1;
__END__
=head1 SEE ALSO
L<Bio::Graphics::Wiggle::Loader>,
L<Bio::Graphics::Panel>,
L<Bio::Graphics::Glyph>,
L<Bio::Graphics::Feature>,
L<Bio::Graphics::FeatureFile>
=head1 AUTHOR
Lincoln Stein E<lt>lstein@cshl.orgE<gt>.
Copyright (c) 2007 Cold Spring Harbor Laboratory
This package and its accompanying libraries is free software; you can
redistribute it and/or modify it under the terms of the GPL (either
version 1, or at your option, any later version) or the Artistic
License 2.0. Refer to LICENSE for the full license text. In addition,
please see DISCLAIMER.txt for disclaimers of warranty.
=cut