nextstrain / nextclade

Viral genome alignment, mutation calling, clade assignment, quality checks and phylogenetic placement
https://clades.nextstrain.org
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Nucleotide insertions not shown in peptide tooltip, causing confusion in case of frameshift due to nt insertion #1520

Open whottel opened 2 months ago

whottel commented 2 months ago

Hello,

I recently uploaded a few Mpox sequences into the the web version of Nextclade. I noticed several of these had a OPG069:45-167 frame shift flagged. Screenshot 2024-09-04 120716 Looking at the results more closely as shown in the screenshot, it is not clear to me where the frame shift is actually occurring. Despite a few nucleatide mutations, it looks like the query sequences should still be in frame but starting at AA 45 an unknown amino acid is indicated.

corneliusroemer commented 2 months ago

Hello @whottel - thanks so much for your question (or potential bug report).

In order to help, could you please share some sequences with which I can try to reproduce what you're seeing? Are they available publicly? If so, you can just send me their accessions, otherwise, you can also email them to me at first name dot last name @unibas.ch - I will treat them confidentially.

Could you also tell me which mpox dataset you were using? Thanks!

whottel commented 2 months ago

The samples in question are not publically available, so I will send a follow-up email as you suggested. And this was analyzed using the Nextclade dataset "Mpox virus (Lineage B.1)".

corneliusroemer commented 2 months ago

@whottel thank you! I'm looking forward to your email and try to find out what's happening here.

corneliusroemer commented 2 months ago

Thanks you, I've received your email and I believe I've figured out what's happening:

There's a 2nt insertion TT after 50117:

Brave Browser 2024-09-04 20 30 07

The insertion isn't shown in the tooltip because I don't think we show insertions in tooltips, I'm not sure why not, I suppose we ought to as it is otherwise confusing. While one can check insertions separately, it's not obvious to users that this would be necessary:

image

It's not quite obvious how we would show an insertion in the tooltip, but some sort of indication would be nice, even if it is just a triangle marker.

Until insertions are shown in the tooltip in gene view, as a workaround, you can look at the frameshift in nucleotide view, where it is shown:

Brave Browser 2024-09-04 20 34 37
whottel commented 2 months ago

Great, thanks! I am now looking in the right place.

corneliusroemer commented 2 months ago

Thanks so much for raising this - while your question is explainable, you are totally correct that the current tooltip is confusing in this regard so I very much appreciate you opening this issue! If you notice any other confusing things in the UI, please let us know!