XEC +Orf1a:A599T+ S:I68F(70 seqs, >10 places)

[xz-keg]

There seems to be a very new and very interesting branch of XEC found by @FedeGueli 。
From branch 13 of sars-cov-2-variants/lineage-proposals#2088
XEC+G2060A(Orf1a:A599T)+C583T+ A21764T(S:I68F)

GISAID query: G2060A,-21766,T3565C, C583T(edited)
No. of seqs: 10(USA 4(GBW from Turkey and Egpyt) France 4 Sweden 1 Czech Republic 1)

First: EPI_ISL_19465899, Czech Republic, 2024-9-17
Latest: EPI_ISL_19472838, USA from Turkey, 2024-9-30

GISAID and cov-spectrum read it as del21764_21769+G21770T, usher also reads this way and then drop it out. The correct mutation shall be :
1: Most SGTF, including the BA.2.86 one, is formed by del21766_21771, not del21767_21772, so it has additional A21766C if read as del21767_21772

2: This branch has additional A21764T, together with A21766C it gets S:I68F.

@AngieHinrichs @corneliusroemer

This branch grows very fast, last week it was only 2. Now it is 10, with samples coming from undersampled regions this could be a superfast branch.

usher

[FedeGueli]

From first sample to 10 in 13 days from 5 countries and 7 regions ( considering three different French provinces) .
After Sept 15:
1/11 samples from Czech republic
1/4 samples from Egypt
2/10 samples from Turkey
1/148 samples from Stockholm Sweden
1/2 samples from Rennes France
2/7 samples from Alpes-Maritimes France
1/235 samples from Rhone France

[FedeGueli]

+1 Netherlands

[xz-keg]

one more from Netherlands

[xz-keg]

There seems to be an additional USA-NY seq without C583T , alter query.

[FedeGueli]

There seems to be an additional USA-NY seq without C583T , alter query.

Please keep both of them , it could be a separate emergence. (former is C583T,G21770T,T3565C)

[FedeGueli]

G2060A,G21770T,T3565C

Just noticed that this sample without G583T is from a 44 days old and it is the first sample in US, it sounds unusual.

[xz-keg]

There seems to be an additional USA-NY seq without C583T , alter query.

Please keep both of them , it could be a separate emergence. (former is C583T,G21770T,T3565C)

Currently we haven't seen XEC with C583T seqs without S:I68F, so it is safe to assume C583T comes after S:I68F.

[FedeGueli]

Currently we haven't seen XEC with C583T seqs without S:I68F, so it is safe to assume C583T comes after S:I68F.

not safe at all in my view. XEC is not that big that you can be sure of that, and more we know that homoplasy of beneficial mutations is very high and the sample is placed in another branch (also Czech sample is placed otherwise now):

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_30da3_e56f0.json?c=userOrOld&label=id:node_7259272

[FedeGueli]

I will start monitoring : G2060A,G21770T,T3565C,-C583T

[xz-keg]

Currently we haven't seen XEC with C583T seqs without S:I68F, so it is safe to assume C583T comes after S:I68F.

not safe at all in my view. XEC is not that big that you can be sure of that, and more we know that homoplasy of beneficial mutations is very high and the sample is placed in another branch (also Czech sample is placed otherwise now): https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_30da3_e56f0.json?c=userOrOld&label=id:node_7259272

That's only one seq that shares another 25521 mutation with it.
S:68 mutation is not displayed on usher (it is first recognized as S:V70F and then removed) so unless they have additional mutations they won't be categorized together.

@AngieHinrichs , is it possible to change the base of BA.2.86* seqs to BA.2.86 instead of sticking to WT base so that S:68 mutations can be recognized on the tree?

[FedeGueli]

That's only one seq that shares another 25521 mutation with it. S:68 mutation is not displayed on usher (it is first recognized as S:V70F and then removed) so unless they have additional mutations they won't be categorized together.

Not very convincing sincerely because there is one at least supporting the separation with zero supporting the mashing up of the two. With HK.3 we have had tons of this. When applying the same reasoning to XBB.1.5 it didnt work well.
one point favouring the reunification is that 25521 is quite homoplasic but for example XBB.1.9.1/.2 different nuc was homoplasic too.

[xz-keg]

That's only one seq that shares another 25521 mutation with it. S:68 mutation is not displayed on usher (it is first recognized as S:V70F and then removed) so unless they have additional mutations they won't be categorized together.

Not very convincing sincerely because there is one at least supporting the separation with zero supporting the mashing up of the two. With HK.3 we have had tons of this. When applying the same reasoning to XBB.1.5 it didnt work well.

Yeah hard to prove or disprove at current. If there's more seqs on the NY branch I may be more convinced to separate emergence. Now it seems just coincidentally gets a T25521 mutation with another UK seq.

[FedeGueli]

That's only one seq that shares another 25521 mutation with it. S:68 mutation is not displayed on usher (it is first recognized as S:V70F and then removed) so unless they have additional mutations they won't be categorized together.

Not very convincing sincerely because there is one at least supporting the separation with zero supporting the mashing up of the two. With HK.3 we have had tons of this. When applying the same reasoning to XBB.1.5 it didnt work well.

Yeah hard to prove or disprove at current. If there's more seqs on the NY branch I may be more convinced to separate emergence. Now it seems just coincidentally gets a T25521 mutation with another UK seq.

to me it will depend if we will see multiple emergences or not of 68F . the appearance of 68T makes me tend to think yes!

[xz-keg]

+4 France +1 Italy, 18 now. All on C583T branch

[xz-keg]

+1 Wales

[FedeGueli]

+1 France (Besancon Bourgogne new province)

I checked its advantage in France and it has still the Lower CI slighty negative vs XEC so we cant be 100% sure of its advantage but certainly the other two CI intervals are quite significant on its potential advantage.
https://cov-spectrum.org/explore/France/AllSamples/Past3M/variants?nextcladePangoLineage=XEC*&nucMutations1=C583T%2CG21770T%2CT3565C&analysisMode=CompareToBaseline&

[xz-keg]

28, Denmark, Spain

[FedeGueli]

28, Denmark, Spain
Also to be noticed the one from Italy via GBW

Ping @corneliusroemer, thx for your recent rounds of designations: this is maybe the last one better not to delay to get designated, please take a look

[FedeGueli]

29 France

[FedeGueli]

30 Ontario

[xz-keg]

New seqs show the seq not on C583T branch really belongs to a second branch. @FedeGueli So I limit this proposal to C583T branch.

@corneliusroemer Designation can start from C583T branch now.

[Over-There-Is]

44

[FedeGueli]

+3 France

[FedeGueli]

50, Wales

[xz-keg]

+1 Hong Kong

@corneliusroemer usher now shows it as S:V70F. Despite the mutation is still incorrect this mutation is separated out to designate accordingly.

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/hgPhyloPlace/subtreeAuspice3_genome_test_67ebd_4ddc0.json?label=id:node_5702813

[xz-keg]

+1 Ireland

[FedeGueli]

+1 Wales

[FedeGueli]

+1 Wales