XEC spike diversity issue #2088

xz-keg · 2024-09-25T03:18:00Z

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 5 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.

Tasks

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Branch 1: XEC+Orf1a:A599T+S:T572I(54 seqs, >10 places) cov-lineages/pango-designation#2803
Branch 2: XEC + S:G252S on the ORF1a:A599T branch (16 in 4 countries ) #1993
Branch 3: Designated XEC.1, XEC + S:K182R (6 , 4 countries) #1869
Branch 4: XEC+Orf1a:A599T+S:L1224F, Query: G25234T,G2060A,C18657T,-24376, 21 seqs, Scotland, USA-OH
Branch 5: XEC+Orf1a:A599T+Orf1b:M2322I+S:A688V,Query: G2060A,G20433T,C23625T, 10 seqs, France, Portugal,Netherlands,Ohio, Spain,Italy
Branch 6: XEC subbranch with S:R346I on Orf1a:A599T branch (5 sequences, 3 countries) #2029
Branch 7: By @cvejris, XEC + Orf1a: A599T (G2060A) + Orf1a: T2274I (C7086T) + S:S680F (C23601T). 9 seqs: 5xGuadeloupe, 2x US, 1xFrance via GBW, 1xWales
Branch 8: XEC+Orf1a:A599T+S:G75R, Query: G21785C,G2060A,-G1681A , 7 seqs, USA, France, Spain,Germany,Netherlands
Branch 9: By @cvejris, XEC+Orf1a:A599T+C11020T+S:E1202Q, XEC + S:E1202Q (22 seqs, 6 countries) cov-lineages/pango-designation#2812
Branch 10, XEC+Orf1a:A599T+S:K182N, Query: G2060, A22108T, C829, 9 seqs, USA, Canary Islands, Netherlands, UK, Denmark
Branch 11, By @cvejris, XEC+Orf1a:A599T+S:G72R, Query: G2060A, G21776A,T3565C, XEC+S:G72R (22 seqs, 11 countries) cov-lineages/pango-designation#2819
Branch 12, By @FedeGueli, XEC+ Orf1a:A599T + S:P561H (C23244A) Query: C23244A,C18657T, C25006T, Samples: 3 Scotland , Sweden, Denmark
Branch 13 by @FedeGueli , XEC +Orf1a:A599T+ C583T + S:I68F XEC +Orf1a:A599T+ S:I68F(25 seqs, >10 places) cov-lineages/pango-designation#2802
Branch 14, XEC+Orf1a:A599T+S:S98F, Query:G2060A,C21855T,C25006T, 6 seqs, USA, Italy, France, Germany
Branch 15 by @cvejris XEC+Orf1a:A599T>Orf1a:G59C ( G440T),S:W152R(T22016A),S:P1263Q (C25350A) Query: G440T,T22016A,C25350A,T21738C Samples: 7 Ireland,Singapore, Netherlands, France
Branch 16, by @JosetteSchoenma XEC+Orf1a:A599T+C3787T,S:I68T, Query: T21771C, G21770A,G2060A, 2 seqs, Netherlands, Germany
Branch 17, XEC+Orf1a:A599T+S:I584V, Query: G2060A,A23312G, 8 seqs, USA, France
Branch 18, XEC+Orf1a:A599T+S:H49Y, Query: C21707T, G2060A, C19716T, 8 seqs, Netherlands, Sweden, UK, USA,France,Poland
Branch 19, XEC+Orf1a:A599T+S:E1202K, Query: G25166A,G2060A, 11 seqs, USA, Canada
branch 20, XEC.2+T7168C+S:G75R, Query: T7168C, G21785C,A4364C, 4 seqs, UK, France,USA
Branch 21, XEC+Orf1a:A599T+S:A262S,Query:G2060A,G22346T,C25006T, 4 seqs, Denmark, Italy,UK, USA
Branch 22 By @cvejris XEC + Orf1a: A599T (G2060A) + M: I52V (A26676G) + S:S680F (C23601T. 5 seqs: 3xSpain, 1xNetherlands, 1xJapan
Branch 23, XEC+Orf1a:A599T,A138T+S:V1228L, Query: G2060A,G677A,G25244T,C19716T, 6 seqs, France, Australia, Ireland, Denmark,USA
Branch 24, XEC+Orf1a:A599T+S:S940F, Query: C24381T,G2060A,C18657T, 3 seqs, Canada, USA,Germany
Branch 25, XEC+Orf1a:A599T+S:L822I, Query: C24026A,G2060A, 6 seqs, Japan, Germany, Italy, Ireland, Sweden
Branch 26, XEC+Orf1a:A599T+S:G181V, Query: G2060A,G22104T,C18657T, 6 seqs, Denmark, Netherlands, Germany, Luxembourg
Branch 27, XEC+Orf1a:A599T+S:W152R(T22016C), Query: T22016C, G2060A,C18657T,C19716T, 7 seqs, UK,Germany, Sweden, Ireland,USA
Branch 28, XEC+Orf1a:A599T+S:H1101Y, Query: C24863T, G2060A,C18657T, 12 seqs,Sweden, Canada, USA
Branch 29, XEC+Orf1a:A599T+S:P681H, Query: C23604A, G2060A,C18657T,C19716T,10 seqs, Denmark, UK, France, Brazil
Branch 30, XEC+Orf1a:A599T+C1102T+S:V1176F,Orf3a:T89I, Query: G25088T,C1102T,G2060A, 5 seqs, Italy, France, Canada, Russia
Branch 31, XEC+Orf1a:A599T+S:L1143F,Orf1b:Q2069K,Query:C24989T, G2060A,C18657T, 6 seqs, Netherlands, Ireland
Options

FedeGueli · 2024-09-25T09:22:30Z

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 · 2024-09-25T10:13:26Z

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.

cvejris · 2024-09-26T17:18:23Z

Branch 7: XEC+Orf1a:A599T+S:S680F (furin), 5seqs (1xFrance, 1xCanada, 3xUS). Arose 2x independently (all US sequences are separated on the Orf1a:T2274I subbranch). All seqs less than 1 month old. Query: G2060A, C23601T

Mydtlwn · 2024-09-27T06:46:40Z

@corneliusroemer

cvejris · 2024-09-28T15:33:23Z

Branch 9: XEC+Orf1a:A599T+S:E1202Q, 2 seqs, France + Ireland. Query: G2060A,C11020T,G25166C

FedeGueli · 2024-09-28T17:23:59Z

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

cvejris · 2024-10-01T20:20:41Z

Branch 10/11: XEC+S:W152R (defining for Centaurus) arose convergently: Branch 10 via T22016A (1xNL, 1xFR). Branch 11 via T22016C (1xIR, 1xUSA). All seqs sampled in September

cvejris · 2024-10-01T20:25:00Z

Branch 12: 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 · 2024-10-01T20:51:26Z

Branch 13: 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

xz-keg · 2024-10-01T21:16:38Z

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 · 2024-10-01T21:39:48Z

Branch 14: XEC+S:P1263L(C25350T), same site as branch 13. 1xSW,1xPL.

xz-keg · 2024-10-02T00:39:59Z

Branch 13: XEC+S:P1263Q(C25350A): 3xSW,1xFR,1xNL. Interestingly, most XEC with P1263Q harbor other "promising" mutations

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 · 2024-10-02T06:38:44Z

Branch 13: XEC+S:P1263Q(C25350A): 3xSW,1xFR,1xNL. Interestingly, most XEC with P1263Q harbor other "promising" mutations

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 · 2024-10-02T08:07:23Z

@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 · 2024-10-02T22:35:02Z

Branch 15: XEC+Orf1a:A599T+S:K182N. 3xNL, 1xENG, 1xCanary Islands (with additional S:M153I). Monophyletic, query: C829T, A22108T

FedeGueli · 2024-10-03T22:27:45Z

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 · 2024-10-03T22:43:17Z

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 · 2024-10-04T15:28:25Z

Branch 16: 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 · 2024-10-05T10:47:02Z

Branch 16: 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 · 2024-10-06T03:05:48Z

G2060A, G21776A,T3565C

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

FedeGueli · 2024-10-06T14:14:50Z

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 · 2024-10-07T16:52:11Z

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

FedeGueli · 2024-10-09T09:50:48Z

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:

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 · 2024-10-10T15:44:38Z

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 · 2024-10-12T04:27:37Z

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.

xz-keg · 2024-10-23T04:57:44Z

add branch 18(S:H49Y) and branch 19(E1202K)
apply a new rule limiting branches with >=5 seqs and >=2 places, or >=3 places only.

Over-There-Is · 2024-10-23T05:37:32Z

Q52L

FedeGueli · 2024-10-23T08:08:32Z

Q52L

i am tracking one with it from Slovenia with A21717T ,T23542C , 3 seqs is it the same?

cvejris · 2024-10-23T08:48:45Z

branch 7 is 22 now, @cvejris you can propose it to main.

Upon closer look, S680F does not appear monophyletic, but heavily convergent. Many sequences are part of larger lineages (defined by C7086T or C7086T+C28093T), which originally lacked S680F. For sequences on the Orf1a:A599T polytomy, I would guess these are convergent too.

xz-keg · 2024-10-23T10:00:04Z

branch 7 is 22 now, @cvejris you can propose it to main.

Upon closer look, S680F does not appear monophyletic, but heavily convergent. Many sequences are part of larger lineages (defined by C7086T or C7086T+C28093T), which originally lacked S680F. For sequences on the Orf1a:A599T polytomy, I would guess these are convergent too.

C7086T is a very convergent mutation. It could be first getting S680F then get C7086T.

FedeGueli · 2024-10-25T08:39:00Z

446I in Wales and Australia

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice2_genome_test_15964_b57db0.json?label=id:node_11721902
still not matching the threshold.
Query:G22899T,C18657T, C19716T,

cvejris · 2024-10-25T16:06:20Z

You too waiting for RBD mutations? :) I´m tracking V445R (3-nuc) - still only 3 seqs from 3 countries, but convergent, not monophyletic

FedeGueli · 2024-10-25T22:53:30Z

You too waiting for RBD mutations? :) I´m tracking V445R (3-nuc) - still only 3 seqs from 3 countries, but convergent, not monophyletic

Ah good to know it is spreading further i saw that too but it was a singlet

xz-keg · 2024-10-26T09:00:43Z

add branch 20, G75R on XEC.2

FedeGueli · 2024-10-27T14:00:40Z

Br.7 up to 29 @cvejris please verify if still splitted in two and if so which one is growing

cvejris · 2024-10-27T17:55:40Z

Br.7 up to 29 @cvejris please verify if still splitted in two and if so which one is growing

More than two. See the distribution of mutations:

There appear two clusters which imo could be considered branches, the rest is either convergent or "phylogenetically illegible":

XEC + Orf1a: A599T (G2060A) + Orf1a: T2274I (C7086T) + S:S680F (C23601T). 9 seqs: 5xGuadeloupe, 2x US, 1xFrance via GBW, 1xWales
XEC + Orf1a: A599T (G2060A) + M: I52V (A26676G) + S:S680F (C23601T. 5 seqs: 3xSpain, 1xNetherlands, 1xJapan

Which should I propose?

FedeGueli · 2024-10-27T19:49:23Z

Br.7 up to 29 @cvejris please verify if still splitted in two and if so which one is growing

More than two. See the distribution of mutations:

There appear two clusters which imo could be considered branches, the rest is either convergent or "phylogenetically illegible":

XEC + Orf1a: A599T (G2060A) + Orf1a: T2274I (C7086T) + S:S680F (C23601T). 9 seqs: 5xGuadeloupe, 2x US, 1xFrance via GBW, 1xWales

XEC + Orf1a: A599T (G2060A) + M: I52V (A26676G) + S:S680F (C23601T. 5 seqs: 3xSpain, 1xNetherlands, 1xJapan

Which should I propose?

none of them i will separate it in two branches

FedeGueli · 2024-10-27T19:49:44Z

Br.17 up to 8 fastly

FedeGueli · 2024-10-27T19:52:02Z

XEC + Orf1a: A599T (G2060A) + M: I52V (A26676G) + S:S680F (C23601T. 5 seqs: 3xSpain, 1xNetherlands, 1xJapan

This has been added as Branch 22 now

cvejris · 2024-10-27T22:49:23Z

S:S31F (C21654T): 5seqs total - 2x XEC.2 (US, Denmark), 3x Orf1a:A599T branch (Germany, France 2x)

xz-keg · 2024-10-29T03:14:20Z

add branch 23(V1228L)
Branch 24(S940F)
Branch 25(L822I)
Branch 26(G181V)
Branch 27(W152R via 22016C)
Branch 28(H1101Y)
Branch 29(P681H)
Branch 30(V1176F)
Branch 31(L1143F)

xz-keg · 2024-10-29T05:05:05Z

Branch 16: XEC+Orf1a:A599T+S:G72R. 5 seqs, 5 countries: Denmark, Netherlands, France (with S:K113R), Canada, GBW from Mexico. Query: G2060A, G21776A,T3565C (edited)

This one(branch 11) is 21 now, please propose it,

cvejris · 2024-10-29T08:01:37Z

Can you please add XEC+ Orf1a:A599T+S:T678I to the list above? Curently 16 seqs (6xCanada, 3xNetherlands, 3xFrance, 2xAustralia, 1xNew Zealand, 1xJapan). Query G2060A, C23595T

xz-keg · 2024-10-29T08:43:09Z

Can you please add XEC+ Orf1a:A599T+S:T678I to the list above? Curently 16 seqs (6xCanada, 3xNetherlands, 3xFrance, 2xAustralia, 1xNew Zealand, 1xJapan). Query G2060A, C23595T

not homoplastic

Over-There-Is · 2024-10-29T14:31:26Z

K150R,K529E,S704L 4, Czech rep.

Over-There-Is · 2024-10-29T14:32:42Z

Q173R

Over-There-Is · 2024-10-29T14:33:37Z

G20062A,C20946T,G22599C,C29535T R346T

Over-There-Is · 2024-10-29T14:35:26Z

S256L

16 now C18657T, C22329T, C24382T

Over-There-Is · 2024-10-29T14:40:12Z

V705I

cvejris · 2024-10-29T14:43:24Z

K150R,K529E,S704L 4, Czech rep.

proposed already #2182

NkRMnZr · 2024-10-30T05:20:46Z

there're several S:A222V branches, major one right under the polytomy (4, 3 from Canada, 1 from USA)

FedeGueli · 2024-10-30T12:49:23Z

Also emergence of S:V308L and (in another branch) S:S704L on XEC.2 backbone in Canada cluster as S:Q173R mentioned by @Over-There-Is

thx @NkRMnZr i ve seen those 222V ones too.

FedeGueli · 2024-10-30T13:30:51Z

There is a singlet in Singapore with S:I68V and S:A475V : C22986T, C29303T,T6451C
pay attenttion that all the tools read it as 68-69del V70V .

FedeGueli · 2024-10-30T23:55:31Z

S:T716I also Canadian Cluster

FedeGueli added Multiple lineages spike diversity XEC Interesting diversity in the tree the tree shows multiple interesting branches labels Sep 25, 2024

xz-keg pinned this issue Sep 26, 2024

cvejris mentioned this issue Oct 29, 2024

XEC+S:G72R (22 seqs, 11 countries) cov-lineages/pango-designation#2819

Open

XEC spike diversity issue #2088

XEC spike diversity issue #2088

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