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BUG: Multiple mutations in one codon cause can cause false amino acid mutation

Open corneliusroemer opened this issue 3 years ago • 1 comments
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When looking at sequence Iran/AN127/2022|EPI_ISL_10195257, I noticed that it was falsely annotated with Q498*.

Nextclade annotates it with Q498Q: image

The reason for Usher's false annotation seems to be the presence of two mutations in one codon.

On an internal branch, I could even see two mutations listed side by side Q498H, Q498* which is clearly not possible.

How do you deal with multiple mutations in one codon? Is this a known limitation by design?

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corneliusroemer avatar Mar 17 '22 00:03 corneliusroemer

Sorry, the web interface uses simple code that translates each nucleotide substitution into its corresponding amino acid substitution independently. I'll add it to the list of badly needed improvements but am not sure when I'll have time to work on it.

AngieHinrichs avatar Mar 17 '22 17:03 AngieHinrichs

I believe this is fixed on dev.usher.bio now - CV.2 and XBB.1.5 are good for testing this. Also a cluster in XBC.2 that has a (probably false) reversion on 23019 that causes S:P486L (e.g. Brunei/7722014505/2022|EPI_ISL_15696712|2022-10-10), with one member of that cluster regaining T23019C restoring 486P (Brunei/7722017695/2022|EPI_ISL_16231620|2022-11-28).

AngieHinrichs avatar Mar 10 '23 06:03 AngieHinrichs

Exciting news, thanks so much @AngieHinrichs! I'll watch out for possible regressions. Can you link to the PR that changed the behaviour? Curious how big it was, what functions were touched, etc - to be able to test better.

corneliusroemer avatar Mar 10 '23 09:03 corneliusroemer

Looks to be working to me. Closing for now.

russcd avatar Apr 23 '23 03:04 russcd