[ensembl-dev] can VEP output the distance of the variant to the exon junction?
Irina Armean
iarmean at ebi.ac.uk
Fri Mar 8 09:33:22 GMT 2019
Hi David,
thanks for the feedback! Yes, the question of reporting the distance of
a variant to the nearest exon junction has come up before.
In your particular case, are you interested in identifying stop gained
and frameshift variants that are/aren't covered by NMD using the 50 bp
rule, or having your own customizable rule?
If you are interested in identifying stop gained and frameshifts that
escape NMD (50bp rule) then this functionality is available and refined
in LOFTEE (https://github.com/konradjk/loftee); it annotates such
variants with LoF LC END_TRUNC, the plugin is taking into consideration
UTR splicing and GERP scores.
If there are cases that you are interested in and are not covered by the
existing plugins, I would be interested to know. Also, we encourage and
accept pull requests on the VEP_plugins
(https://github.com/Ensembl/VEP_plugins) git repository for plugins that
would be for wider interest.
Kind regards,
Irina
On 07/03/2019 17:39, David Tamborero wrote:
> Hi Irina, I have been playing with the plugin (thanks for that again!).
>
> What I am actually interested is in the distance of the variant to the
> next exon-exon junction, as defined by the CDS and not by the
> 'absolute' bps (including UTR), which is what determines whether the
> NMD will act (see here
> <https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002296>),
> which is what i want to detect. I was not clear enough on that, apologies.
>
> In any case, what you re retrieving now is actually also interesting
> for other evaluations. Maybe you could include what you have now and
> also the coding sequence values ? Again, note that I address these
> calculations by my own ad hoc scripts, so consider to implement it
> (together with the location of the frameshift-induced stop codon
> mentioned before) just if you believe that it can be of interest for
> the community (which i think it does!)
>
> br
> d
>
> El lun., 4 mar. 2019 a las 18:33, David Tamborero
> (<david.tamborero at gmail.com <mailto:david.tamborero at gmail.com>>) escribió:
>
> thta s great, i m currently travelling but i will try it as soon
> as i back to the lab (and feedback you guys as appropriate)
>
> thanks again!
> d
>
> El vie., 1 mar. 2019 a las 16:27, Irina Armean (<iarmean at ebi.ac.uk
> <mailto:iarmean at ebi.ac.uk>>) escribió:
>
> Hi David,
>
> The NearestExonJB.pm plugin is now available on github
> https://github.com/Ensembl/VEP_plugins. This plugin reports
> the nearest exon junction boundary (exon id, bp distance,
> start or end, exon length) within the affected transcript.
>
> I hope you find it useful.
>
> Best regards,
>
> Irina*
> *
>
> On 25/02/2019 08:40, David Tamborero wrote:
>> That s fantastic, thanks!
>>
>> Have a great week
>> D
>>
>> El vie., 22 feb. 2019 17:48, Irina Armean <iarmean at ebi.ac.uk
>> <mailto:iarmean at ebi.ac.uk>> escribió:
>>
>> Hi David,
>>
>> Thanks for the clarification and the positive feedback
>> for the team. We do our best to make the desired
>> functionality available in due time, sometimes it's
>> easier/faster than other times.
>>
>> We plan to add a VEP plugin within the next week, which
>> will report the nearest exon junction boundary (exon id,
>> bp distance, start or end, exon length) for variants in
>> the protein coding region, this should answer your case
>> and also provide some additional use cases.
>>
>> For the case of frameshifts and premature stop codons,
>> they are handled more efficiently in the main VEP code
>> and is more complex to update quickly however we plan to
>> cover this use case in the near future.
>>
>> I will come back with a mail once the plugin is in.
>>
>> Best regards,
>>
>> Irina
>>
>>
>> On 21/02/2019 17:17, David Tamborero wrote:
>>> Hi Irina, thanks for your answer, it is always awesome
>>> how diligent you are guys;
>>>
>>> my wishlist:
>>>
>>> - in my case, what i m interested in is in the distance
>>> (nucleotides) from my variant 'within' the exon (ie
>>> protein coding-affecting variant) to the next exon
>>> junction. But note that other users may be interested in
>>> other distances, as those that you mention.
>>>
>>> - FYI, i m interested in that info for the variants that
>>> create preamture stop codons, so I can estimate whether
>>> it will be likely that the non-mediated decay is
>>> triggered (which depends on how far it falls regarding
>>> the last junction of the transcript). Note that --for
>>> the same reason-- I m also interested in, given a
>>> frameshift mutation, where the new 'cryptic' stop codon
>>> will be placed. I currently calculate it by actually
>>> using the VEP info that can be parsed from the HGVSp
>>> column (e.g. p.Glu5ValfsTer5, meaning the stop codon in
>>> 5 codons after the first 'ectopic codon' created by the
>>> frameshift, if I remember well).
>>>
>>> Again, I currently address both cases by my own ad hoc
>>> scripts, but I thought that you already 'have' the info
>>> to easily output these things, which I think it can be
>>> of interest for the community (and surely more neat that
>>> my creepy coding!)
>>>
>>> hope it makes sense!
>>> br
>>> d
>>>
>>> El jue., 21 feb. 2019 a las 17:12, Irina Armean
>>> (<iarmean at ebi.ac.uk <mailto:iarmean at ebi.ac.uk>>) escribió:
>>>
>>> Dear David,
>>>
>>> Thanks for the question. We currently don't have
>>> this functionality however we can easily add the
>>> distance to the closest exon.
>>>
>>> To clarify, are you interested in getting the
>>> distance to the nearest exon junction for the
>>> variants only when it affects a protein coding
>>> transcript or also when they are upstream/downstream
>>> of genes for example?
>>>
>>> Best regards,
>>>
>>> Irina
>>>
>>>
>>> On 21/02/2019 11:09, David Tamborero wrote:
>>>> Dear all,
>>>>
>>>> is any flag (which I cannot find) so the VEP output
>>>> includes the distance of the (coding) variant to
>>>> the closest exon junction?
>>>>
>>>> If not, somebody has a recommended fancy approach
>>>> to do so? (My current approach is 'just' to match
>>>> with my own script the VEP output for a given
>>>> transcript with the exon coordinates data that can
>>>> be retrieved in e.g. BioMart)
>>>>
>>>> many thanks in advance!
>>>> d
>>>>
>>>> _______________________________________________
>>>> Dev mailing listDev at ensembl.org <mailto:Dev at ensembl.org>
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>>>
>>> --
>>> Irina Armean PhD, Bioinformatican
>>> Ensembl Variation, EMBL-EBI, Hinxton, UK
>>> iarmean[at]ebi.ac.uk <http://ebi.ac.uk> | A3 - 135
>>>
>> --
>>
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