A variation is defined by its alleles and a pair of flanking sequence, e.g.:<div><br></div><div>ATCGTACTGTACGTGTTTATCG [A/G] TGACTTACTATCGTATGACTT</div><div><br></div><div>dbSNP (or in some cases Ensembl) use sequence alignment algorithms to map this sequence to the genomic reference sequence. If it maps to the reverse strand, we create a variation_feature on the reverse strand. In some cases the sequence may map more than once, hence a variation object can have multiple associated variation_feature objects. This is easier to see on the web views:</div>
<div><br></div><div><a href="http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78197743;vdb=variation">http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78197743;vdb=variation</a></div><div><br></div><div>
As I mentioned, it makes our lives easier if most things are on the forward strand, so we "flip" as many of these reverse strand mappings as we can. We only do this when a variation has a single mapping to the reverse strand.</div>
<div><br></div><div>Will<br><br><div class="gmail_quote">On 2 February 2011 16:17, Oliver, Gavin <span dir="ltr"><<a href="mailto:gavin.oliver@almacgroup.com">gavin.oliver@almacgroup.com</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex;">
<div lang="EN-US" link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">Cool, thanks.</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">What determines the strand it goes on?</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma"> <a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>
[mailto:<a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>] <b><span style="font-weight:bold">On Behalf Of </span></b>Will
McLaren<br>
<b><span style="font-weight:bold">Sent:</span></b> 02 February 2011 16:15</span></font></p><div class="im"><font size="2" face="Tahoma"><br>
<b><span style="font-weight:bold">To:</span></b> Oliver,
Gavin<br>
<b><span style="font-weight:bold">Cc:</span></b> Graham Ritchie;
<a href="mailto:dev@ensembl.org" target="_blank">dev@ensembl.org</a><br>
</font></div><font size="2" face="Tahoma"><b><span style="font-weight:bold">Subject:</span></b> Re: [SPAM] - Re: [SPAM] -
Re: [SPAM] - Re: [ensembl-dev] Transcript variation alleles - Email found in
subject - Email found in subject - Email found in subject</font><p></p>
</div><div><div></div><div class="h5">
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">variation_feature objects have a strand just like all features in
Ensembl - most are on the forward strand (as this makes our life easier!) but
many are also on the reverse strand.</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">As I mentioned earlier, you can check this using:</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">$vf->seq_region_strand</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">which will return a value
of 1 (forward) or -1 (reverse).</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">On 2 February 2011 16:09, Oliver, Gavin
<<a href="mailto:gavin.oliver@almacgroup.com" target="_blank">gavin.oliver@almacgroup.com</a>>
wrote:</span></font></p>
<div link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">Ok…</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">So as it stands the alleles I am returning are genomic and called
via variation features. Are they always relative to the forward strand?</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma"> <a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>
[mailto:<a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>]
<b><span style="font-weight:bold">On Behalf Of </span></b>Will McLaren<br>
<b><span style="font-weight:bold">Sent:</span></b> 02 February 2011 16:04<br>
<b><span style="font-weight:bold">To:</span></b> Oliver,
Gavin<br>
<b><span style="font-weight:bold">Cc:</span></b> Graham Ritchie; <a href="mailto:dev@ensembl.org" target="_blank">dev@ensembl.org</a><br>
<b><span style="font-weight:bold">Subject:</span></b> [SPAM] - Re: [SPAM] - Re:
[SPAM] - Re: [ensembl-dev] Transcript variation alleles - Email found in
subject - Email found in subject - Email found in subject</span></font></p>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Well yes, of
course it depends on what you mean!</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">A transcript
object in Ensembl represents the region of the genome that generates the cDNA,
not the mRNA itself - this is the only thing that we'd be able to transfer the
variation_feature object to, as I don't think there is an Ensembl object
representing the mRNA.</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Will</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">On 2 February 2011
15:54, Oliver, Gavin <<a href="mailto:gavin.oliver@almacgroup.com" target="_blank">gavin.oliver@almacgroup.com</a>>
wrote:</span></font></p>
<div link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">P.S.</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">Should it not be the other way around?</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">i.e. if the transcript originates from the same strand as the
variation feature then the alleles will be different? As the transcript will
be the reverse complement of the strand it originated on?</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">Or have I tied my head in a knot?</span></font></p>
<div>
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma"> <a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>
[mailto:<a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>]
<b><span style="font-weight:bold">On Behalf Of </span></b>Will McLaren<br>
<b><span style="font-weight:bold">Sent:</span></b> 02 February 2011 15:41<br>
<b><span style="font-weight:bold">To:</span></b> Oliver,
Gavin<br>
<b><span style="font-weight:bold">Cc:</span></b> Graham Ritchie; <a href="mailto:dev@ensembl.org" target="_blank">dev@ensembl.org</a><br>
<b><span style="font-weight:bold">Subject:</span></b> [SPAM] - Re: [SPAM] - Re:
[ensembl-dev] Transcript variation alleles - Email found in subject - Email
found in subject</span></font></p>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">There is no direct
method to do this (if I'm following you exactly).</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">If the transcript
is on the same strand as the variation_feature (use $vf->seq_region_strand
and $transcript->seq_region_strand), then the transcript alleles will be the
same; if they are different, then you will need to reverse complement the
alleles:</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">use
Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">my
$new_allele_string;</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">foreach my
$allele(split /\//, $vf->allele_string) {</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> reverse_comp($allele);</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> $new_allele_string
.= $allele.'/';</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">}</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">$new_allele_string
=~ s/\/$//;</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">We can add this
functionality as $vf->transfer() if people would find it useful.</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Will</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">On 2 February 2011
15:27, Oliver, Gavin <<a href="mailto:gavin.oliver@almacgroup.com" target="_blank">gavin.oliver@almacgroup.com</a>>
wrote:</span></font></p>
<div link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">How would I go about pulling the transcriptomic one?</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma"> <a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>
[mailto:<a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>]
<b><span style="font-weight:bold">On Behalf Of </span></b>Will McLaren<br>
<b><span style="font-weight:bold">Sent:</span></b> 02 February 2011 15:27<br>
<b><span style="font-weight:bold">To:</span></b> Oliver,
Gavin<br>
<b><span style="font-weight:bold">Cc:</span></b> Graham Ritchie; <a href="mailto:dev@ensembl.org" target="_blank">dev@ensembl.org</a><br>
<b><span style="font-weight:bold">Subject:</span></b> Re: [SPAM] - Re: [ensembl-dev]
Transcript variation alleles - Email found in subject</span></font></p>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">In this case, as
Graham says, the alleles will be the genomic alleles, since you are calling
from a variation_feature object.</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Will</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">On 2 February 2011
15:21, Oliver, Gavin <<a href="mailto:gavin.oliver@almacgroup.com" target="_blank">gavin.oliver@almacgroup.com</a>>
wrote:</span></font></p>
<div link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">I’m using
transcriptvariation->variation_feature->allele_string</span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma"> <a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>
[mailto:<a href="mailto:wmclaren@gmail.com" target="_blank">wmclaren@gmail.com</a>]
<b><span style="font-weight:bold">On Behalf Of </span></b>Will McLaren<br>
<b><span style="font-weight:bold">Sent:</span></b> 02 February 2011 15:20<br>
<b><span style="font-weight:bold">To:</span></b> Graham Ritchie<br>
<b><span style="font-weight:bold">Cc:</span></b> Oliver,
Gavin; <a href="mailto:dev@ensembl.org" target="_blank">dev@ensembl.org</a><br>
<b><span style="font-weight:bold">Subject:</span></b> [SPAM] - Re:
[ensembl-dev] Transcript variation alleles - Email found in subject</span></font></p>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Hi Gavin,</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">What method and
object type are you using to get the alleles? It's not clear from your email.</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Thanks</span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"> </span></font></p>
</div>
<div>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Will</span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">On 2 February 2011
15:11, Graham Ritchie <<a href="mailto:grsr@ebi.ac.uk" target="_blank">grsr@ebi.ac.uk</a>>
wrote:</span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Hi Gavin,<br>
<br>
The alleles of a transcript variation always represent the genomic base change.<br>
<br>
Cheers,<br>
<br>
Graham<br>
<br>
Ensembl variation</span></font></p>
<div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><br>
<br>
On 2 Feb 2011, at 15:02, Oliver, Gavin
wrote:<br>
<br>
> Hi,<br>
><br>
> When I pull transcript variation alleles via the API, does the allele
shown (e.g. A/T) represent the genomic base change, or the transcriptomic one?<br>
><br>
> Gavin<br>
><br>
><br>
> The contents of this message and any attachments to it are confidential
and may be legally privileged. If you have received this message in error, you
should delete it from your system immediately and advise the sender.<br>
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><br>
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><br>
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</div>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">The contents of this message and any attachments to it are
confidential and may be legally privileged. If you have received this message
in error, you should delete it from your system immediately and advise the
sender.</span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Group (UK) Limited, registered no. NI061368.
Almac Sciences Limited, registered no. NI041550. Almac Discovery Limited,
registered no. NI046249. Almac Pharma Services Limited, registered no.
NI045055. Almac Clinical Services Limited, registered no. NI041905.
Almac Clinical Technologies Limited, registered no. NI061202. Almac Diagnostics
Limited, registered no. NI043067. All preceding companies are registered
in Northern Ireland with a
registered office address of Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63
5QD, UK.
</span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Sciences (Scotland)
Limited, registered in Scotland
no. SC154034. </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Clinical Services LLC, Almac Clinical Technologies
LLC, Almac Diagnostics LLC, Almac Pharma Services LLC and Almac Sciences LLC
are Delaware
limited liability companies and Almac Group Incorporated is a Delaware
Corporation. More information on the Almac Group can be found on the
Almac website: <a href="http://www.almacgroup.com" target="_blank">www.almacgroup.com</a></span></font></p>
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<p class="MsoNormal"><strong><b><font size="3" color="blue" face="Times New Roman"><span style="font-size:12.0pt;color:blue"> </span></font></b></strong></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">The contents of this message and any attachments to it are
confidential and may be legally privileged. If you have received this message
in error, you should delete it from your system immediately and advise the
sender.</span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Group (UK) Limited, registered no. NI061368.
Almac Sciences Limited, registered no. NI041550. Almac Discovery Limited,
registered no. NI046249. Almac Pharma Services Limited, registered no.
NI045055. Almac Clinical Services Limited, registered no. NI041905.
Almac Clinical Technologies Limited, registered no. NI061202. Almac
Diagnostics Limited, registered no. NI043067. All preceding companies are
registered in Northern Ireland
with a registered office address of Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63
5QD, UK.
</span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Sciences (Scotland)
Limited, registered in Scotland
no. SC154034. </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Clinical Services LLC, Almac Clinical Technologies
LLC, Almac Diagnostics LLC, Almac Pharma Services LLC and Almac Sciences LLC
are Delaware
limited liability companies and Almac Group Incorporated is a Delaware
Corporation. More information on the Almac Group can be found on the
Almac website: <a href="http://www.almacgroup.com" target="_blank">www.almacgroup.com</a></span></font></p>
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<p class="MsoNormal"><strong><b><font size="3" color="blue" face="Times New Roman"><span style="font-size:12.0pt;color:blue"> </span></font></b></strong></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">The contents of this message and any attachments to it are
confidential and may be legally privileged. If you have received this message
in error, you should delete it from your system immediately and advise the
sender.</span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Group (UK) Limited, registered no. NI061368.
Almac Sciences Limited, registered no. NI041550. Almac Discovery Limited,
registered no. NI046249. Almac Pharma Services Limited, registered no. NI045055.
Almac Clinical Services Limited, registered no. NI041905. Almac Clinical
Technologies Limited, registered no. NI061202. Almac Diagnostics Limited,
registered no. NI043067. All preceding companies are registered in Northern Ireland with a registered office
address of Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD,
UK. </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Sciences (Scotland)
Limited, registered in Scotland
no. SC154034. </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Clinical Services LLC, Almac Clinical Technologies
LLC, Almac Diagnostics LLC, Almac Pharma Services LLC and Almac Sciences LLC
are Delaware
limited liability companies and Almac Group Incorporated is a Delaware
Corporation. More information on the Almac Group can be found on the
Almac website: <a href="http://www.almacgroup.com" target="_blank">www.almacgroup.com</a></span></font></p>
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<p class="MsoNormal"><strong><b><font size="3" color="blue" face="Times New Roman"><span style="font-size:12.0pt;color:blue"> </span></font></b></strong></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">The contents of this message and any attachments to it are
confidential and may be legally privileged. If you have received this message
in error, you should delete it from your system immediately and advise the sender.</span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Group (UK) Limited, registered no. NI061368.
Almac Sciences Limited, registered no. NI041550. Almac Discovery Limited,
registered no. NI046249. Almac Pharma Services Limited, registered no.
NI045055. Almac Clinical Services Limited, registered no. NI041905.
Almac Clinical Technologies Limited, registered no. NI061202. Almac
Diagnostics Limited, registered no. NI043067. All preceding companies are
registered in Northern Ireland
with a registered office address of Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63
5QD, UK.
</span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Sciences (Scotland)
Limited, registered in Scotland
no. SC154034. </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black"> </span></font></p>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span lang="EN-GB" style="font-size:12.0pt;color:black">Almac Clinical Services LLC, Almac Clinical Technologies
LLC, Almac Diagnostics LLC, Almac Pharma Services LLC and Almac Sciences LLC are
Delaware
limited liability companies and Almac Group Incorporated is a Delaware
Corporation. More information on the Almac Group can be found on the
Almac website: <a href="http://www.almacgroup.com" target="_blank">www.almacgroup.com</a></span></font></p>
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<font face="Tahoma" size="2">
<p class="MsoNormal"><strong><b><span style="font-size:12pt;color:blue"><font face="Times New Roman"> </font></span></b></strong></p>
<p class="MsoNormal"><font color="#000000"><span lang="EN-GB" style="font-family:'Times New Roman'">The contents of this message and any attachments to it are confidential and may be legally privileged. If you have received this message in error, you should delete it from your system immediately and advise the sender.</span></font></p>
<p class="MsoNormal"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'"> </span></p>
<p class="MsoNormal"><font color="#0000ff"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'">Almac Group (UK) Limited, registered no. NI061368.<span> </span>Almac Sciences Limited, registered no. NI041550.<span> </span>Almac Discovery Limited, registered no. NI046249. <span> </span>Almac Pharma Services Limited, registered no. NI045055.<span> </span>Almac Clinical Services Limited, registered no. NI041905.<span> </span>Almac Clinical Technologies Limited, registered no. NI061202. <span> </span>Almac Diagnostics Limited, registered no. NI043067.<span> </span>All preceding companies are registered in Northern Ireland with a registered office address of Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD, UK. <span> </span></span></font></p>
<p class="MsoNormal"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'"> </span></p>
<p class="MsoNormal"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'">Almac Sciences (Scotland) Limited, registered in Scotland no. SC154034. </span></p>
<p class="MsoNormal"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'"> </span></p>
<p class="MsoNormal"><span lang="EN-GB" style="color:black;font-family:'Times New Roman'">Almac Clinical Services LLC, Almac Clinical Technologies LLC, Almac Diagnostics LLC, Almac Pharma Services LLC and Almac Sciences LLC are Delaware limited liability companies and Almac Group Incorporated is a Delaware Corporation. More information on the Almac Group can be found on the Almac website: <a href="http://www.almacgroup.com" target="_blank">www.almacgroup.com</a></span></p>
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