[ensembl-dev] No longer able to download human gene sequence with minor allele frequency filter AND highlighting since v111 release

[Benjamin Moore]

Hi Benjamin,

Thank you for reporting this error with the sequence download options. 
This behaviour is the result of a known issue where variants are missing 
MAF data in the latest Ensembl release (Ensembl 111). More information 
can be found on the known bugs page on our blog:

https://www.ensembl.info/known-bugs/ensembl-111/

This data will be available again in Ensembl 113, which is due to be 
released later this year. In the meantime, we suggest using the Ensembl 
110 archive (https://jul2023.archive.ensembl.org/index.html) to access 
this data, as you have already found.

We apologise for any inconvenience.

Best wishes

Ben

On 29/02/2024 21:14, Story Benjamin wrote:
>
> Hi all,
>
> Not sure if this is the right contact point for a bioinformatics bug 
> (we have a support ticket open via Fabienne Maurer but I’ve heard 
> progress is limited).
>
> I’m writing this with some potential critical implications. Our lab 
> techs were using Ensembl to extract gene sequences for designing 
> Sanger primers to validate variants in the parents of our pre-natal 
> patients. I’m not sure if we are alone in the world to do the primer 
> design this way or if it is just us.
>
> Starting sometime after December 28^th (first fault detection on Jan 
> 15^th ), the rich text format (RTF) output from the main ensemble 
> website is no longer displaying any variant coloration when you apply 
> MAF filtering (potentially with release 111? Maybe dbSNP related?).
>
> Usually, we remove highlighting from variants with a minor allele 
> frequency (MAF) of less than 0.01% to avoid rare variants so we can 
> solely visualize the common polymorphisms. Otherwise, we risk 
> designing a primer which could provide a false-negative result for a 
> patient/parent (i.e. if one of the primers fail to anneal due to 
> inherent variation in the population).
>
> Currently when the MAF < 0.01% filter is applied all 
> “coloration/highlighting” (i.e. a proxy for MAF) for the variants is 
> NOT output to the RTF file.
>
> Luckily, I’m aware of the Ensembl archives and this was able to solve 
> our immediate problem.
>
> However, in case anyone else is using a similar method I think it 
> would be good to fix the underlying issue.
>
> Steps to reproduce:
>
>  1. Visit transcript exon page.
>      1. Working :
>         http://jul2023.archive.ensembl.org/Homo_sapiens/Transcript/Exons?db=core;g=ENSG00000075624;r=7:5526409-5563902;t=ENST00000646664
>      2. Broken:
>         http://ensembl.org/Homo_sapiens/Transcript/Exons?db=core;g=ENSG00000075624;r=7:5526409-5563902;t=ENST00000646664
>  2. Click ‘Download Sequence’ (just below
>  3. Set ‘File format’ to RTF (Word-compatible)
>  4. For the option ‘Hide variants by frequency (MAF)’ set it to ‘Hide
>     rare, MAF < 0.01%’
>  5. Click ‘Download’
>
> If you start with 1a you get a sequence with highlighted variants 
> based on MAF (with the rare ones excluded, i.e. un-highlighted)
>
> If you start with 1b you don’t have any significant highlighting.
>
> Note that if you don’t apply step 4 you get all the highlighting for 
> all variants regardless of MAF (which still works for both 1a and 1b) 
> – suggesting its related to the filtering.
>
> I tried on multiple OS, browsers, computers, ensembl-mirrors, and the 
> issue seems to stem from the v111 release.
>
> Hope this helps.
>
> Thanks,
>
> Ben
>
>
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-- 
Dr. Ben Moore (he/him)
Ensembl Outreach Manager

European Bioinformatics Institute (EMBL-EBI)
European Molecular Biology Laboratory
Wellcome Trust Genome Campus
Hinxton
Cambridge
CB10 1SD
UK

bmoore at ebi.ac.uk
+44 (0)1223 494265
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