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Designate JN.1.15 (S:A688V)
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corneliusroemer committed Feb 1, 2024
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6 comments on commit 1406788

@FedeGueli
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@FedeGueli FedeGueli commented on 1406788 Feb 1, 2024

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ATTENTION @corneliusroemer are you sure this is monophyletic? many sequences are displaced in different trees, but the most worrying thing that there is a treee that includes subtrees with defining mutations of main JN.1 branches or undesignated ones: https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice4_genome_test_d399_c29d20.json?c=country&label=id:node_6896692
Screenshot 2024-02-02 alle 00 46 22

Could you check please? i find sequences used to designate this one in that very dubious tree look at Israel/ICH-741200493/2024|EPI_ISL_18781202 for example

cc @AngieHinrichs

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The designated sequences all fall on one branch in the 2024-02-01 tree: JN.1 > C12899T (ORF1ab:P4212S). It's true that the little branch with Czech Republic and Wales has C774T (ORF1ab:T170I), the only defining mutation of JN.1.4, so there's a question of whether C12899T or C774T came first for those sequences -- but JN.1.4 is much larger than this little branch (thousands vs 55), so yeah, I wonder why those sequences were placed on this little branch instead of on JN.1.4. There are two sequences from California that have G22111T(S:Q183H) which is the defining mutation of JN.1.9, so that's also a coin toss (and JN.1.9 has hundreds of sequences so again I don't know why the sequences were placed on this little branch, and JN.1.9 is defined by a Spike mutation unlike this little ORF1ab).

@FedeGueli did you spot any other lineage-defining mutations? Do you want me to try to re-place those sequences?

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the G16269A branch (from Israel) has 457 sequences ,
the C14708T has 14 (35% with 688V)
S:Q183H is JN.1.9
Orf1a:t170I is JN.1.4

Not all of the designated sequences has orf1a:P4212S , to me this could be solved excluding sequences without it and starting this lineage from Orf1a:P4241S (C12899T )
Screenshot 2024-02-02 alle 09 15 14
https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_5d799_ca40e0.json?label=id:node_6896699

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@aviczhl2 aviczhl2 commented on 1406788 Feb 2, 2024

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The designated sequences all fall on one branch in the 2024-02-01 tree: JN.1 > C12899T (ORF1ab:P4212S). It's true that the little branch with Czech Republic and Wales has C774T (ORF1ab:T170I), the only defining mutation of JN.1.4, so there's a question of whether C12899T or C774T came first for those sequences -- but JN.1.4 is much larger than this little branch (thousands vs 55), so yeah, I wonder why those sequences were placed on this little branch instead of on JN.1.4. There are two sequences from California that have G22111T(S:Q183H) which is the defining mutation of JN.1.9, so that's also a coin toss (and JN.1.9 has hundreds of sequences so again I don't know why the sequences were placed on this little branch, and JN.1.9 is defined by a Spike mutation unlike this little ORF1ab).

@FedeGueli did you spot any other lineage-defining mutations? Do you want me to try to re-place those sequences?

The algorithm prefer to assign seqs to smaller branches if given multiple choices. Maybe because they think defining mutations of large branches is more likely to be convergent(as defining mutations from large branches are also very likely to be distributed in various locations due to artefact/recomb) so seqs with both mutations are more likely to be put under smaller branches.

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Comments on commits are hard to find - it'd be better to open an issue if there's something to discuss, i.e. if it's more than just tagging with an issue.

You're totally right that quite a few branches are suspicious and might have acquired 688V independently.

Going through all mutations coming off the polytomy of the Usher 688V branch:

  • 12899T: not a major branch in JN.1
  • G16269A: Indeed common in Israel without 688V (400 seqs)
  • 774T: Indeed very common (20% of JN.1)
  • C14708T: Exists without 688V, but 688V is around 50%
  • G22111T: Indeed common but could be homoplasy as well
  • C26894T: 1% of JN.11

I'd be ok with reverting this designation, in particular as we lack a single 1-nuc-off-JN.1 688V .

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Ok thank you sorry next time i will open one issue.

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