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

[Story Benjamin]

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 28th (first fault detection on Jan 15th), 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.
     *   Working : http://jul2023.archive.ensembl.org/Homo_sapiens/Transcript/Exons?db=core;g=ENSG00000075624;r=7:5526409-5563902;t=ENST00000646664
     *   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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