<div dir="ltr">You will probably see odd behaviour if you mix versions of the script / API / caches / databases. Feel free to experiment, though we can't support such setups obviously.<div><br></div><div>It works fine for me on 75 or 79 (i.e. using "git checkout --release 75" in ensembl-tools, ensembl-variation, ensembl-core)</div><div><br></div><div>Will</div></div><div class="gmail_extra"><br><div class="gmail_quote">On 26 March 2015 at 11:26, Guillermo Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div text="#000066" bgcolor="#FFFFFF">
I guess it's a problem with my API installation then.<br>
<br>
If I install latest API(79) and continue to use
<a href="http://variant_effect_predictor.pl" target="_blank">variant_effect_predictor.pl</a> from version 75 will it continue working
or I'll get conflicts/weird behaviours?<br>
<br>
Thanks!<br>
<br>
Regards,<br>
Guillermo.<div><div class="h5"><br>
<br>
<br>
<div>On 26/03/15 11:53, Will McLaren wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">Example output (I set $Data::Dumper::Maxdepth =
1;):
<div><br>
</div>
<div>> echo "rs699" | perl -I ~/Git/guillermo/vep/ <a href="http://variant_effect_predictor.pl" target="_blank">variant_effect_predictor.pl</a>
-plugin Clinvar -data -force -db 75<br>
</div>
<div>
<div>2015-03-26 10:51:38 - Reading input from STDIN (or maybe
you forgot to specify an input file?)...</div>
<div>2015-03-26 10:51:38 - Starting...</div>
<div>2015-03-26 10:51:38 - Detected format of input file as id</div>
<div>2015-03-26 10:51:38 - Read 1 variants into buffer</div>
<div>2015-03-26 10:51:38 - Checking for existing variations</div>
<div>[===================================================================================================================================================================================================]
[ 100% ]</div>
<div>2015-03-26 10:51:38 - Reading transcript data from cache
and/or database</div>
<div>[===================================================================================================================================================================================================]
[ 100% ]</div>
<div>2015-03-26 10:51:38 - Retrieved 4 transcripts (0 mem, 0
cached, 4 DB, 0 duplicates)</div>
<div>2015-03-26 10:51:38 - Analyzing chromosome 1</div>
<div>2015-03-26 10:51:38 - Analyzing variants</div>
<div>[===================================================================================================================================================================================================]
[ 100% ]</div>
</div>
<div>
<div>2015-03-26 10:51:38 - Calculating consequences</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '2853',</div>
<div> 'name' => undef,</div>
<div> 'description' => 'HYPERTENSION,
ESSENTIAL, SUSCEPTIBILITY TO'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '20384',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'Susceptibility_to_progression_to_renal_failure_in_IgA_nephropathy'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '20369',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'Preeclampsia,_susceptibility_to'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '26451',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'HYPERTENSION,_ESSENTIAL,_SUSCEPTIBILITY_TO'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '1',</div>
<div> 'name' => 'HGMD_MUTATION',</div>
<div> 'description' => 'Annotated by HGMD
but no phenotype description is publicly available'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '6522',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'COSMIC:tumour_site:large_intestine'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '6529',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'COSMIC:tumour_site:breast'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '2853',</div>
<div> 'name' => undef,</div>
<div> 'description' => 'HYPERTENSION,
ESSENTIAL, SUSCEPTIBILITY TO'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '20384',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'Susceptibility_to_progression_to_renal_failure_in_IgA_nephropathy'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '20369',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'Preeclampsia,_susceptibility_to'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '26451',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'HYPERTENSION,_ESSENTIAL,_SUSCEPTIBILITY_TO'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '1',</div>
<div> 'name' => 'HGMD_MUTATION',</div>
<div> 'description' => 'Annotated by HGMD
but no phenotype description is publicly available'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '6522',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'COSMIC:tumour_site:large_intestine'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>$VAR1 = bless( {</div>
<div> 'adaptor' =>
'Bio::EnsEMBL::Variation::DBSQL::PhenotypeAdaptor=HASH(0x43c39a8)',</div>
<div> 'dbID' => '6529',</div>
<div> 'name' => undef,</div>
<div> 'description' =>
'COSMIC:tumour_site:breast'</div>
<div> }, 'Bio::EnsEMBL::Variation::Phenotype' );</div>
<div>2015-03-26 10:51:38 - Processed 1 total variants (1
vars/sec, 1 vars/sec total)</div>
<div>2015-03-26 10:51:38 - Wrote stats summary to
variant_effect_output.txt_summary.html</div>
<div>2015-03-26 10:51:38 - Finished!</div>
</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On 26 March 2015 at 10:43, Guillermo
Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div text="#000066" bgcolor="#FFFFFF"> Hello Will,<br>
<br>
I already had enabled "check_existing" on my VEP config
template, however I followed your advice and updated code
to force in the new() method with your code.<br>
I'm still getting no prints of line 64:<br>
<span><br>
print</span><span>
Dumper(</span><span>$pf</span><span>-></span><span>phenotype());<br>
</span><br>
Are you getting any output printed? As I said I get no
errors but nothing is printed neither. This data dumper
should be printing result of phenotype() method call.<br>
<br>
Regards,<br>
Guillermo.
<div>
<div><br>
<br>
<br>
<div>On 26/03/15 11:05, Will McLaren wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">I think perhaps you haven't enabled
--check_existing; this is required for
$vf->{existing} to get populated.<br>
<div><br>
</div>
<div>You can force it on in the new() method of
your plugin:</div>
<div><br>
</div>
<div>$self->{config}->{check_existing} = 1;</div>
<div><br>
</div>
<div>It then works for me on release/75 and
release/79.</div>
<div><br>
</div>
<div>Will</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On 25 March 2015 at
17:35, Guillermo Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div text="#000066" bgcolor="#FFFFFF"> Hello
Will,<br>
<br>
With your explanations I'm trying to call
phenotype (as you said I was accessing the
hashref directly).<br>
I'm using input set you linked. However my
local Ensembl installation is v75.<br>
<br>
This is the code of the plugin:<br>
<a href="https://github.com/guillermomarco/vep/blob/master/Clinvar.pm" target="_blank">https://github.com/guillermomarco/vep/blob/master/Clinvar.pm</a><br>
<br>
I'm getting absolutelty no info nor errors.
I've no idea if this is an issue with my
database/API version or with the plugin code
itself.<br>
<br>
Regards,<br>
Guillermo.
<div>
<div><br>
<br>
<br>
<div>On 16/03/15 17:50, Will McLaren
wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">The "is_significant"
field is an internal flag that
doesn't necessarily have the meaning
you expect; it is used to
distinguish between genuine reported
associations and e.g.
non-significant associations
reported from genome-wide studies.
<div><br>
</div>
<div>You should not see undef for
phenotype; I suspect you are
accessing the hashref directly
($pf->{phenotype}) rather than
making the method call
($pf->phenotype()).</div>
<div><br>
</div>
<div>You could try <a href="ftp://ftp.ensembl.org/pub/release-79/variation/vcf/homo_sapiens/Homo_sapiens_clinically_associated.vcf.gz" target="_blank">ftp://ftp.ensembl.org/pub/release-79/variation/vcf/homo_sapiens/Homo_sapiens_clinically_associated.vcf.gz</a>
as a test input set.</div>
<div><br>
</div>
<div>Will</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On 16 March
2015 at 16:39, Guillermo Marco
Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote">
<div> Hi Will,<br>
<br>
Thank you for your quick
response! Very clarifying.<br>
<br>
I guess that the way to
retrieve ClinVar data I posted
is correct. With my test
dataset I've only seen
"is_significant" values of "1"
and undef 'phenotype' values.
I think I need a synthetic vcf
with ClinVar annotation
variants to very that the
plugin is working.<br>
<br>
I've been looking on Ensembl
website for a test dataset. I
think you don't provide any
right? Correct me if I'm
wrong.<br>
<br>
Thanks!<br>
<br>
Regards,<br>
Guillermo.
<div>
<div><br>
<br>
<div>On 16/03/15 16:16,
Will McLaren wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">Hi
Guillermo,
<div><br>
</div>
<div>To get the rest
of that data in the
table you need to
access the
additional
attributes of the
PhenotypeFeature
object, something
like:</div>
<div><br>
</div>
<div>my $attr =
$pfs->[0]->get_all_attributes;<br>
</div>
<div>print
"$_:".$attr->{$_}."\t"
for keys %$attr;</div>
<div>print "\n;</div>
<div><br>
</div>
<div>Regards</div>
<div><br>
</div>
<div>Will</div>
<div><br>
</div>
<div>More info: the
reason these data
are stored as
attributes is due to
the diverse data
sources and types
that we import into
our phenotype
schema; to create a
database column and
corresponding API
method for each data
type (p-value,
review status, risk
allele, external ID
etc etc) would be
cumbersome and
inefficient. To this
end we provide a few
methods that
shortcut the
attribute approach
for the most common
data types;
everything else must
be accessed through
the attributes
method. This is a
common theme across
the Ensembl API.</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On
13 March 2015 at
12:03, Guillermo
Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote">
<div> Hi,<br>
<br>
I'm trying to
retrieve ClinVar
information with
the code example
you provided.<span><br>
<br>
my $self =
shift;<br>
my $tva =
shift;<br>
my $vf =
$tva->variation_feature;<br>
my $pfa =
$self->{config}->{reg}->get_adaptor('human','variation','phenotypefeature');<br>
<br>
foreach my
$known_var(@{$vf->{existing}
|| []}) {<br>
foreach my
$pf(@{$pfa->fetch_all_by_object_id($known_var->{variation_name})})
{<br>
</span>
if
($pf->{'source'}
eq
"dbSNP_ClinVar"){<br>
print
"$pf->{'source'}\t$pf->{'external_id'}\t$pf->{'is_significant'}\t$pf->{'phenotype'}\n",
;<br>
}<br>
}<br>
}<br>
<br>
As you can see
I'm "filtering"
the results to
only output
phenotype
feature when
source is
dbSNP_ClinVar. I
don't know why
but I guess
filtering should
be done when
doing the
"fetch_all".<br>
<br>
On the other
hand I'm trying
to retrieve
Disease, Source
and Clinical
Significance
from this
example table: <a href="http://www.ensembl.org/Homo_sapiens/Variation/Phenotype?db=core;r=8:19955518-19956518;v=rs268;vdb=variation;vf=266" target="_blank">http://www.ensembl.org/Homo_sapiens/Variation/Phenotype?db=core;r=8:19955518-19956518;v=rs268;vdb=variation;vf=266</a><br>
<br>
I think I'm
doing something
wrong I got
totally lost in
Phenotypefeature.<br>
<br>
Regards,<br>
Guillermo.
<div>
<div><br>
<br>
<div>On
02/03/15
16:05, Will
McLaren wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">If
you enable the
--check_existing
flag when you
run the VEP,
you'll be able
to see any
known
co-located
variants
attached to
the
VariationFeature
object in your
plugin:
<div><br>
</div>
<div>sub run {</div>
my $self =
shift;
<div> my $tva
= shift;</div>
<div> my $vf
=
$tva->variation_feature;</div>
<div><br>
</div>
<div> foreach
my
$known_var(@{$vf->{existing}
|| []}) {</div>
<div> # do
stuff</div>
<div> }</div>
<div>}</div>
<div><br>
</div>
<div>The
$known_var is
not an API
object but a
simple hashref
with a number
of fields;
you're
probably
interested in
$known_var->{clin_sig}</div>
<div><br>
</div>
<div>However,
as I
mentioned,
this is the
only data that
is stored in
the cache. To
access the
rating and the
specific
disease
association,
you'll need to
make calls to
the database
by getting an
adaptor,
something
like:</div>
<div><br>
</div>
<div>
<div>sub run {</div>
<div> my
$self = shift;</div>
<div> my $tva
= shift;</div>
<div> my $vf
=
$tva->variation_feature;</div>
<div> my $pfa
=
$self->{config}->{reg}->get_adaptor('human','variation','phenotypefeature');</div>
<div><br>
</div>
<div> foreach
my
$known_var(@{$vf->{existing}
|| []}) {</div>
<div>
foreach my
$pf(@{$pfa->fetch_all_by_object_id($known_var->{variation_name})})
{</div>
<div> #
do stuff</div>
<div> }</div>
<div> }</div>
<div>}</div>
</div>
<div><br>
</div>
<div>Be aware
that this will
access the
database, so
unless you
have a local
copy please
don't run this
sort of code
on genome-wide
VCFs using our
public DB
server.</div>
<div><br>
</div>
<div>Regards</div>
<div><br>
</div>
<div>Will</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On
2 March 2015
at 14:47,
Guillermo
Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote">
<div> Hi Will,<br>
<br>
Indeed I'm
looking to
retrieve this
information
from VEP
plugin.<br>
<br>
Regards,<br>
Guillermo.
<div>
<div><br>
<br>
<div>On
02/03/15
15:25, Will
McLaren wrote:<br>
</div>
<blockquote type="cite">
<div dir="ltr">Hi
Guillermo,
<div><br>
</div>
<div>The
detailed
ClinVar
information is
stored against
PhenotypeFeature
objects (each
SNP/disease
pairing gets
its own entry
in ClinVar,
e.g. <a href="http://www.ncbi.nlm.nih.gov/clinvar/RCV000019691.2" target="_blank">http://www.ncbi.nlm.nih.gov/clinvar/RCV000019691.2</a>, <a href="http://www.ncbi.nlm.nih.gov/clinvar/RCV000019692.2/" target="_blank">http://www.ncbi.nlm.nih.gov/clinvar/RCV000019692.2/</a>, <a href="http://www.ncbi.nlm.nih.gov/clinvar/RCV000019693.2/" target="_blank">http://www.ncbi.nlm.nih.gov/clinvar/RCV000019693.2/</a>
for rs699).</div>
<div><br>
</div>
<div>The
rating (and
indeed the
clinical
significance)
is stored as
an attribute
on the
PhenotypeFeature
object; you
can retrieve
this with the
get_all_attributes()
method.</div>
<div><br>
</div>
<div>See <a href="http://www.ensembl.org/info/docs/Doxygen/variation-api/classBio_1_1EnsEMBL_1_1Variation_1_1PhenotypeFeature.html" target="_blank">http://www.ensembl.org/info/docs/Doxygen/variation-api/classBio_1_1EnsEMBL_1_1Variation_1_1PhenotypeFeature.html</a>
and <a href="http://www.ensembl.org/info/docs/api/variation/variation_tutorial.html#phenotype" target="_blank">http://www.ensembl.org/info/docs/api/variation/variation_tutorial.html#phenotype</a>
for more info.</div>
<div><br>
</div>
<div><span>Bio::EnsEMBL::Variation::</span><span>Utils::VEP::get_clin_sig()
is an internal
method that
you should not
use.</span></div>
<div><span><br>
</span></div>
<div><span>The
VEP cache
contains the
list of
clinical
significance
states for
each variant,
but neither
the disease
association or
the rating. If
you want help
getting access
to this data
via a plugin,
let me know as
it's a little
more involved
than the API
methods above
(though it is
faster as no
database
access is
required).</span><br>
</div>
<div><br>
</div>
<div>Regards</div>
<div><br>
</div>
<div>Will
McLaren</div>
<div>Ensembl
Variation</div>
</div>
<div class="gmail_extra"><br>
<div class="gmail_quote">On
2 March 2015
at 14:06,
Guillermo
Marco Puche <span dir="ltr"><<a href="mailto:guillermo.marco@sistemasgenomicos.com" target="_blank">guillermo.marco@sistemasgenomicos.com</a>></span>
wrote:<br>
<blockquote class="gmail_quote">
<div> Dear
devs,<br>
<br>
I'm looking
forward to
retrieve
ClinVar
information
and add it to
VEP
annotation.
From my
understanding
I should be
able to
retrieve
"Clinical
significance"
and "ClinVar
Rating".<br>
<br>
I've been
looking the
Varation API,
and I'm
confused. I
guess for
significance I
should use
Bio::EnsEMBL::Variation::Utils::VEP::get_clin_sig()
or
Bio::EnsEMBL::Variation::VariationFeature::get_all_clinical_significance_states().<br>
<br>
What about
ClinVar
rating? Is it
possible to
retrieve it
from API?<br>
<br>
Thanks!<br>
<br>
Regards,<br>
Guillermo.<br>
<br>
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<fieldset></fieldset>
</blockquote>
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<br></blockquote></div><br></div>