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XEC/XEK spike diversity issue (Updated as of Dec 22) #2088

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xz-keg opened this issue Sep 25, 2024 · 207 comments
Open
25 of 60 tasks

XEC/XEK spike diversity issue (Updated as of Dec 22) #2088

xz-keg opened this issue Sep 25, 2024 · 207 comments

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@xz-keg
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xz-keg commented Sep 25, 2024

It seems that there is, and will be a lot of spike diversity in XEC. Better gather them in one issue.
Only count for branches with more than 10 seqs from 2 places, or from 3 or more places (NEW)

GPT Model trained on August data(seqs before XEC appears) predicts 4 spike mutations for XEC on top potential mutation list: S:T572I, S:R346T, S:N185D, S:A688V.

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@FedeGueli
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FedeGueli commented Sep 25, 2024

Very good idea, i will try to help. do u prefer direct editing or highlighting in the comments?

I would require also that the lineage has to be sampled at least once in September ( or last 30 days) to avoid dead ends
If you agree .

@xz-keg
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xz-keg commented Sep 25, 2024

Very good idea, i will try to help. do u prefer direct editing or highlighting in the comments?

I would require also that the lineage has to be sampled at least once in September ( or last 30 days) to avoid dead ends If you agree .

Sure, you can do direct editing.

@xz-keg xz-keg pinned this issue Sep 26, 2024
@cvejris
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cvejris commented Sep 26, 2024

Branch X: XEC+Orf1a:A599T+S:S680F (furin), 5seqs (1xFrance, 1xCanada, 3xUS). Arose 2x independently (all US sequences are separated on the Orf1a:T2274I subbranch = XEC.9, edited). All seqs less than 1 month old. Query: G2060A, C23601T

@Mydtlwn
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Mydtlwn commented Sep 27, 2024

@corneliusroemer

@cvejris
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cvejris commented Sep 28, 2024

Branch X: XEC+Orf1a:A599T+S:E1202Q, 2 seqs, France + Ireland. Query: G2060A,C11020T,G25166C

@FedeGueli
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Br.7 went to 8 with three GBW samples from Peru' (2 patients)

@cvejris
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cvejris commented Oct 1, 2024

Branch X: XEC+S:W152R (defining for Centaurus) arose convergently: Branch X via T22016A (1xNL, 1xFR). Branch 11 via T22016C (1xIR, 1xUSA). All seqs sampled in September

@cvejris
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cvejris commented Oct 1, 2024

Branch X: XEC+S:T678I (C23595T), furin-adjacent. 4xCAN, 2xFR, 2xUSA. Convergent: one on the Orf1a:I1367L, the rest on the Orf1a:A599T polytomy. All seqs sampled in September

@cvejris
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cvejris commented Oct 1, 2024

Branch X: XEC+S:P1263Q(C25350A): 3xSW,1xFR,1xNL. Convergent (Swedish seqs on the C27630T subbranch of Orf1a:A599T, the rest on the Orf1a:A599T polytomy).
Interestingly, most XEC with P1263Q harbor other "promising" mutations
image

@xz-keg
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xz-keg commented Oct 1, 2024

Branch 10: XEC+S:W152R (defining for Centaurus) arose convergently: i. via T22016A (1xNL, 1xFR) ii. via T22016C (1xIR, 1xUSA). All seqs sampled in September

Please separate these branches and ensure every branch is monoplyetic.

@cvejris
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cvejris commented Oct 1, 2024

Branch X: XEC+S:P1263L(C25350T), same site as branch 13. 1xSW,1xPL.

@xz-keg
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xz-keg commented Oct 2, 2024

Branch X: XEC+S:P1263Q(C25350A): 3xSW,1xFR,1xNL. Interestingly, most XEC with P1263Q harbor other "promising" mutations image

Please check with usher before proposing. They seem to be on different usher branches.
https://genome-test.gi.ucsc.edu/cgi-bin/hgPhyloPlace

If they are on different usher branches it is likely they emerge separately and shouldn't be treated as one. Unless you provide reason (artifact, usher-flip flop, convergent other mutations like branch 7, etc. ) to merge them.

@cvejris
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cvejris commented Oct 2, 2024

Branch X: XEC+S:P1263Q(C25350A): 3xSW,1xFR,1xNL. Interestingly, most XEC with P1263Q harbor other "promising" mutations image

Please check with usher before proposing. They seem to be on different usher branches. https://genome-test.gi.ucsc.edu/cgi-bin/hgPhyloPlace

If they are on different usher branches it is likely they emerge separately and shouldn't be treated as one. Unless you provide reason (artifact, usher-flip flop, convergent other mutations like branch 7, etc. ) to merge them.

IMO, at present the relatively low number of XEC seqs makes it hard to correctly assess the phylogeny, the resolution is still insufficient. The total XEC Usher tree still places most seqs on polytomy.
My contributions should not be treated as lineage proposals. I look for mutations which may be beneficial for the virus. They might be i. founder mutations for a monophyletic lineage which spread to different countries, or ii. the same AA substitution arising independently on different background in different countries. It does not make that much difference - both scenarios may in theory indicate selective advantage conferred by the mutations.
I edited my contributions by adding notes about convergence for the mutations where I think there was one :)

@FedeGueli
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@aviczhl2 i think soon we will be force to raise the parameters to three places and 10 seqs, i tell this because in my previous experience with spike diversity issues it rapidly becomes very mess or too long with the opposite effect to risk hiding something fast instead of highlighting it. It is not yet the moment but we shopuld think about it.

@cvejris
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cvejris commented Oct 2, 2024

Branch X: XEC+Orf1a:A599T+S:K182N. 3xNL, 1xENG, 1xCanary Islands (with additional S:M153I). Monophyletic, query: C829T, A22108T

@FedeGueli
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FedeGueli commented Oct 3, 2024

Not a Branch but worth tracking: XEC + Orf1a:A599T+ S:A475V
Query:T8416C,C22986T,T3565C
Samples: 3
Places: Netherlands, 2 regions (Gelderman, Zuit Holland)

@FedeGueli
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FedeGueli commented Oct 3, 2024

Solved 5 now from Br.8 also from Germany it looks interesting

Deleted for mistake the query of BR.8 i m re building it ( i fear it is not monophyletic though)

@cvejris
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cvejris commented Oct 4, 2024

Branch X: XEC+Orf1a:A599T+S:G72R. 5 seqs, 5 countries: Denmark, Netherlands, France (with S:K113R), Canada, GBW from Mexico. Query: G2060A, G21776A,T3565C (edited)

@FedeGueli
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FedeGueli commented Oct 5, 2024

Branch X: XEC+Orf1a:A599T+S:G72R. 5 seqs, 5 countries: Denmark, Netherlands, France (with S:K113R), Canada, GBW from Mexico. Query: G2060A, G21776A,T3565C (edited)

i ve added T3565C to exclude old samples.

@xz-keg
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xz-keg commented Oct 6, 2024

G2060A, G21776A,T3565C

You can directly edit the task list. But be cautious on cvejris proposals that may not be monophyletic.

@FedeGueli
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FedeGueli commented Oct 6, 2024

G2060A, G21776A,T3565C

You can directly edit the task list. But be cautious on cvejris proposals that may not be monophyletic.

yeah i m a bit confused about the branch numbering . @cvejris i suggest just to add the lineage you find without a branch number

@FedeGueli
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XEC+ Orf1a:A599T + S:P561H (C23244A)
Query: C23244A,C18657T, C25006T,
Samples: 2
Countries: 2 Scotland , Sweden

@FedeGueli
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FedeGueli commented Oct 9, 2024

Important (likely): XEC got S:I68F (by Gisiad correctly) ( read as S:-70F by USher, Covspectrum and Nextclade ) :
Xec> C583T > S:I68F (G21770T)
Query: C583T,G21770T,T3565C
Samples: 4
Countries 4 France, Rep Czech, Sweden , Egypt (via GBW)
Tree:
Screenshot 2024-10-09 alle 11 50 30
https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_18030_6500e0.json?c=userOrOld&label=id:node_11692317

Now added as branch 13

Ping @corneliusroemer here something to watch

@FedeGueli
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Important (likely): XEC got S:I68F (by Gisiad correctly) ( read as S:-70F by USher, Covspectrum and Nextclade ) : Xec> C583T > S:I68F (G21770T) Query: C583T,G21770T,T3565C Samples: 4 Countries 4 France, Rep Czech, Sweden , Egypt (via GBW)
Now added as branch 13

Jumped to 7 with a batch from France, 2 different provinces

@xz-keg
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xz-keg commented Oct 12, 2024

Important (likely): XEC got S:I68F (by Gisiad correctly) ( read as S:-70F by USher, Covspectrum and Nextclade ) : Xec> C583T > S:I68F (G21770T) Query: C583T,G21770T,T3565C Samples: 4 Countries 4 France, Rep Czech, Sweden , Egypt (via GBW)
Now added as branch 13

Jumped to 7 with a batch from France, 2 different provinces

+3 GBW from Turkey, you can propose it to main.

@FedeGueli
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FedeGueli commented Dec 15, 2024

the XEC+475V + orf3a:S60F + Orf6:L52F Ontario cluster grew to 14 and recent samples. One to watch if it manages to exit the cluster. (Q: C6582T, T19230C, C22522T,)

@FedeGueli
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FedeGueli commented Dec 15, 2024

Br 17 went to 34
updated everything some more are dead some growing interestingly. still too ealry to propose in my view

@FedeGueli FedeGueli changed the title XEC/XEK spike diversity issue (Updated as of Dec 10) XEC/XEK spike diversity issue (Updated as of Dec 15) Dec 15, 2024
@FedeGueli
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A former Scottish cluster now found also in Denmark with S:S514F
query: C23103T,A1803G
Samples: 5 all from november
https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/hgPhyloPlace/subtreeAuspice1_genome_test_1f349_f6f260.json?label=id:node_7264304

should i add it? cc @xz-keg

@xz-keg
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xz-keg commented Dec 16, 2024

A former Scottish cluster now found also in Denmark with S:S514F query: C23103T,A1803G Samples: 5 all from november https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/hgPhyloPlace/subtreeAuspice1_genome_test_1f349_f6f260.json?label=id:node_7264304

should i add it? cc @xz-keg

yeah pls

@FedeGueli
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A former Scottish cluster now found also in Denmark with S:S514F query: C23103T,A1803G Samples: 5 all from november https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/hgPhyloPlace/subtreeAuspice1_genome_test_1f349_f6f260.json?label=id:node_7264304
should i add it? cc @xz-keg

yeah pls

Br.56 now

@FedeGueli
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Br.25 , formerly thought dead now jumped to 15 with a batch from Japan , 4 of the new samples have S:P384S that is predicted by J Bloom to be a hotspot for immuno escape.,

@Over-There-Is
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Br.25 , formerly thought dead now jumped to 15 with a batch from Japan , 4 of the new samples have S:P384S that is predicted by J Bloom to be a hotspot for immuno escape.,

also NDPFL137-141M

@Over-There-Is
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All 10 Japanese sequences of Branch 25 have C21997T.

@FedeGueli
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All 10 Japanese sequences of Branch 25 have C21997T.

yeah i saw that and the deletion even a bit messy on nextclade, i will re fromulate the br.25 to include all the nodes (it is hard to specify for sub brannches in multiple lineages proposalS) thx for checking

@FedeGueli
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Br.25 , formerly thought dead now jumped to 15 with a batch from Japan , 4 of the new samples have S:P384S that is predicted by J Bloom to be a hotspot for immuno escape.,

also NDPFL137-141M

to me it is
S:N137M + 138-141del D142D V143V 144del
or
S:137-140del S:L141M D142D V143V 144del

@xz-keg
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xz-keg commented Dec 18, 2024

branch 17 is now 35 @FedeGueli I'll propose it?

@corneliusroemer
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corneliusroemer commented Dec 18, 2024

Thoughts on this branch in XEC.8?

It looks like it could be a KP.2.3--(3506-?22k?)-XEC.8 recombinant, where the donor on KP.2.3 side is the German/Dutch branch from KP.2.3 with 593T and 3505

Google Chrome Beta 2024-12-18 21 44 53 Google Chrome Beta 2024-12-18 21 46 48

query for recombinant: C593T, C3505T, G24193T

query for minor donor: C593T, C3505T, A15402G

Timeline and location fits a recombination event in Germany around July/August 2024.

@xz-keg
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xz-keg commented Dec 19, 2024

branch 47 designated XEK.4 via cov-lineages/pango-designation@7cb9d21

branch 54 designated XEC.16 via cov-lineages/pango-designation@4256d9b

FedeGueli referenced this issue in cov-lineages/pango-designation Dec 19, 2024
FedeGueli referenced this issue in cov-lineages/pango-designation Dec 19, 2024
@xz-keg
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xz-keg commented Dec 19, 2024

Thoughts on this branch in XEC.8?

It looks like it could be a KP.2.3--(3506-?22k?)-XEC.8 recombinant, where the donor on KP.2.3 side is the German/Dutch branch from KP.2.3 with 593T and 3505

Google Chrome Beta 2024-12-18 21 44 53 Google Chrome Beta 2024-12-18 21 46 48
query for recombinant: C593T, C3505T, G24193T

query for minor donor: C593T, C3505T, A15402G

Timeline and location fits a recombination event in Germany around July/August 2024.

C593T and C3505T are XEK specific, likely XEK/XEC.8 recombinant given XEK is much more prevalent than its KP.2.3 parent.
wait it also have C28291A rev which is weird since 28884 is not reverted so this part is unlikely due to recomb.

@FedeGueli
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FedeGueli commented Dec 19, 2024

There is an interesting branch of XEC that in its least branch evolved S:T33K and S:141-144del:
Query: G12749A,C27972A (5/6 with 141-144del, 4/6 w T33K)
tree:
Screenshot 2024-12-19 alle 18 19 15
https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/hgPhyloPlace/subtreeAuspice1_genome_test_2eafc_4541e0.json?c=userOrOld&label=id:node_7256969

For now just a cluster.

@FedeGueli
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FedeGueli commented Dec 20, 2024

Br.53 (444R) one more from NZL (new)

@xz-keg
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xz-keg commented Dec 22, 2024

Add branch 57 (XEC.2+R765L)
branch 58 (XEC.1+A67V)

raise threshold for 2 place branches to 10 seqs. (still no threshold if detected in 3 different places)

@FedeGueli FedeGueli changed the title XEC/XEK spike diversity issue (Updated as of Dec 15) XEC/XEK spike diversity issue (Updated as of Dec 22) Dec 22, 2024
@FedeGueli
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Br.55 appears to be fast.- everything just updated

@FedeGueli
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Added several -s to Br.29 (681H)

@Over-There-Is
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C8146T,T2803C,G25249T M1229I CA-ON

@Over-There-Is
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Over-There-Is commented Dec 24, 2024

XEC.2.2 + T572I T1104C, T9508C, C23277T 3 UK, Ireland

@Over-There-Is
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Another XEC.8+S:A688V, C23625T,C28603T, not on T27995C branch

@FedeGueli
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Another XEC.8+S:A688V, C23625T,C28603T, not on T27995C branch

added as branch 59

@xz-keg
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xz-keg commented Dec 26, 2024

branch 55 is 32 now.

@xz-keg
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xz-keg commented Dec 26, 2024

XEC.2.2 + T572I T1104C, T9508C, C23277T 3 UK, Ireland

added as branch 60.

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