[ensembl-dev] Change in SIFT and PolyPhen score

[Sarah Hunt]

Hi Wallace,

Both NCBI and Ensembl stopped creating new gene annotations on GRCh37 a 
long time ago - late 2013 and early 2014 respectively.

NCBI released a mapping of the then current set of GRCh38-derived RefSeq 
transcripts to GRCh37 in January 2017. (See: 
ftp://ftp.ncbi.nlm.nih.gov/genomes/H_sapiens/GRCh37.p13_interim_annotation/README 
for details).  We added these to our GRCh37 database in Ensembl 90, in 
the summer of 2017, with SIFT and PolyPhen2 results.

We are not expecting any new transcript data for GRCh37, so there is 
nothing new to analyse. If we switch to new versions of SIFT or 
Polyphen2 or find ways to reduce the failure rate, we may update the 
GRCh37 results. We don't currently plan a version change and it would be 
announced if we did this as results would change.

Best wishes,

Sarah

On 04/01/2019 02:16, Wallace Ko wrote:
> Hi Sarah,
>
> Thanks for your explanation.
> Does it mean that SIFT and PolyPhen2 scores for RefSeq transcript for 
> GRCh37 are now also calculated (instead of mapping from Ensembl 
> transcript) but at a longer update interval?
>
> Best,
> Wallace
>
>
> On Thu, Jan 3, 2019 at 1:09 AM Sarah Hunt <seh at ebi.ac.uk 
> <mailto:seh at ebi.ac.uk>> wrote:
>
>
>     Hi Wallace,
>
>     Apologies for the partial response.
>
>     Prior to release 90, we did not calculate SIFT and PolyPhen2
>     scores for RefSeq transcripts, though they were available for
>     those with translations identical to an Ensembl transcript.
>     Although the GRCh37 transcript sets have been frozen for some
>     time, we update our GRCh37 variation data roughly annually, and
>     results from the analysis of new Ensembl GRCh38 translations would
>     be made available then.
>
>     The difference in SIFT results - the change from no data to a
>     prediction -  will be due to results for a transcript matching
>     NM_000540.2 becoming available in release 88.
>
>     We re-ran our PolyPhen pipeline for e!90 when we noticed slightly
>     lower missingness rates after a change of hardware. We suspected
>     changes in the cluster set up led to less high-memory alignment
>     failures, but were not in a position to test this.
>
>     We now routinely calculate SIFT and PolyPhen2 scores for RefSeq
>     transcripts for our GRCh38 releases, which happen roughly
>     quarterly. Due to the scheduling of when RefSeq transcript data
>     becomes available in our release process, these scores are
>     available in VEP the release after the transcripts are available.
>
>     Best wishes,
>
>     Sarah
>
>
>>     On 28/12/2018 11:12, Wallace Ko wrote:
>>>     Hello,
>>>
>>>     For the variant chr19:g.39075695C>T, the SIFT and PolyPhen score
>>>     are changed in recent versions of VEP.
>>>
>>>     VEP 	HGVSc 	SIFT 	PolyPhen
>>>     87 	NM_000540.2:c.14759C>T 	- 	unknown(0)
>>>     88 	NM_000540.2:c.14759C>T 	deleterious(0) 	unknown(0)
>>>     89 	NM_000540.2:c.14759C>T 	deleterious(0) 	unknown(0)
>>>     90 	NM_000540.2:c.14759C>T 	deleterious(0)
>>>     probably_damaging(0.998)
>>>
>>>
>>>     The above table shows that for NM_000540.2:c.14759C>T, SIFT is
>>>     changed from  '-' to 'deleterious(0)' since VEP 88 and PolyPhen
>>>     is changed from 'unknown(0)' to 'probably_damaging(0.998)' 
>>>     since VEP 90.
>>>
>>>     There is no change in software version of SIFT (sift5.2.2) and
>>>     PolyPhen (2.2.2) in these versions of VEP, so I wonder what
>>>     causes to the change in the prediction scores.
>>>
>>>     Thank you.
>>>
>>>     Regards,
>>>     Wallace Ko
>>>
>>>     _______________________________________________
>>>     Dev mailing listDev at ensembl.org  <mailto:Dev at ensembl.org>
>>>     Posting guidelines and subscribe/unsubscribe info:http://lists.ensembl.org/mailman/listinfo/dev
>>>     Ensembl Blog:http://www.ensembl.info/
>>
>>     _______________________________________________
>>     Dev mailing listDev at ensembl.org  <mailto:Dev at ensembl.org>
>>     Posting guidelines and subscribe/unsubscribe info:http://lists.ensembl.org/mailman/listinfo/dev
>>     Ensembl Blog:http://www.ensembl.info/
>     _______________________________________________
>     Dev mailing list Dev at ensembl.org <mailto:Dev at ensembl.org>
>     Posting guidelines and subscribe/unsubscribe info:
>     http://lists.ensembl.org/mailman/listinfo/dev
>     Ensembl Blog: http://www.ensembl.info/
>
>
> _______________________________________________
> Dev mailing list    Dev at ensembl.org
> Posting guidelines and subscribe/unsubscribe info: http://lists.ensembl.org/mailman/listinfo/dev
> Ensembl Blog: http://www.ensembl.info/
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://mail.ensembl.org/pipermail/dev_ensembl.org/attachments/20190104/a6315887/attachment.html>