Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially South Africa only but now in various countries, growth advantage inside South Africa against XBB.1.5) #1643

xz-keg · 2023-02-10T04:46:04Z

I'm proposing this as @FedeGueli suggests me to propose a separate issue on XBB.1.5+S:K97T

Around 30% of the South African XBB.1.5 sequences have S:K97T, while none occur in elsewhere.

First sequence: 2022-12-28, EPI_ISL_16574576
Last sequence: 2023-1-31, EPI_ISL_16823497

GISAID query: Spike_K97T,Spike_V83A, Spike_F486P, Spike_F490S
Countries: South Africa
No of sequences: 23

Sequences:
EPI_ISL_16520549, EPI_ISL_16574576, EPI_ISL_16580285,
EPI_ISL_16580293, EPI_ISL_16583854, EPI_ISL_16583857,
EPI_ISL_16738189-16738190, EPI_ISL_16738230, EPI_ISL_16738236,
EPI_ISL_16738239, EPI_ISL_16750841, EPI_ISL_16750887,
EPI_ISL_16750892-16750893, EPI_ISL_16750908, EPI_ISL_16823453,
EPI_ISL_16823460, EPI_ISL_16823462, EPI_ISL_16823471-16823472,
EPI_ISL_16823495, EPI_ISL_16823497

There are multiple branches contain this mutation.

Branch 1: XBB.1.5+S:K97T （16 seqs)
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_35321_59dfc0.json?f_userOrOld=uploaded%20sample&label=id:node_8012864

Branch 2: XBB+S:486P+orf1ab:Q556K, M:E19Q(reversion)+S:G252V+M:D3N+S:K444T,S:L452R+S:K97T (4 seqs)
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice2_genome_35321_59dfc0.json?c=gt-S_97

Branch 3: XBB.1.5+C10369T+S:K97T,orf3a:T151I (2 seqs)
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice3_genome_35321_59dfc0.json?c=gt-S_97

Branch 4: On a quite messed-up branch full of "reversions". (1 seq)

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice4_genome_35321_59dfc0.json?c=gt-S_97

corneliusroemer · 2023-02-10T12:49:06Z

Occurring multiple times in messy trees and just one country raises artefact suspicion, so let's watch this for a while before designating (if at all).

xz-keg · 2023-02-11T00:41:46Z

Occurring multiple times in messy trees and just one country raises artefact suspicion, so let's watch this for a while before designating (if at all).

Usher seems quite messy on XBB.1.5 sub-trees, there are many huge branches of "S:V252G reversions" on the tree, as more than 5000 XBBs with S:486P do not have S:G252V (XBB.1 defining mutation), and usher seems to be categorizing most of them into XBB.1.5, and create back-and-forth 252G-252V reversion--re-reversion--re-re-reversion sub-trees that makes everything very messy.

xz-keg · 2023-02-11T01:06:38Z

This is an "XBB.1.5+S:V252G reversion" branch of 700+(902-129=773) descendants.
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_3952b_601230.json?f_userOrOld=uploaded%20sample&label=id:node_7992907

Another branch with 300+(404-83=321) descendants
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice3_genome_3952b_601240.json?label=id:node_8008601

Lots of other similar sub-trees, too.

corneliusroemer · 2023-02-11T01:32:22Z

Ah that calls for branch specific masking 🙃 @AngieHinrichs

The flip flopping is due to artefactual reversions to reference combined with that site also often being N due to dropout.

But generally, these flip flop branches are not of highest quality so need to be careful.

FedeGueli · 2023-02-11T08:35:01Z

Flip flop branches...great definition!

xz-keg · 2023-02-11T14:01:00Z

Ah that calls for branch specific masking 🙃 @AngieHinrichs

The flip flopping is due to artefactual reversions to reference combined with that site also often being N due to dropout.

But generally, these flip flop branches are not of highest quality so need to be careful.

Yeah, most of the 5000+ non-252 XBB.1.5 sequences are N dropouts.

However, 451 of them do have S:252G. Are they really XBB.1.5? Artefact or XBBs with S:486P? Where shall they be placed?

xz-keg · 2023-02-14T03:18:43Z

35 viruses now.
Exported from South Africa to Singapore. EPI_ISL_16905270

All 12 new seqs are from branch 1.

xz-keg · 2023-02-15T03:07:52Z

36 seqs now.

xz-keg · 2023-02-18T03:22:25Z

50 seqs as of 2.17

FedeGueli · 2023-02-20T22:42:51Z

There has been a big upload of xbb.1.5 + S:k97T from South Africa , the total count now doubled to over 100

xz-keg · 2023-02-21T08:27:56Z

Yeah, 106 seqs now, and it is appearing in USA too.

EPI_ISL_16982302

Newark International Airport, probably passenger from South Africa?

There has been a big upload of xbb.1.5 + S:k97T from South Africa , the total count now doubled to over 100

corneliusroemer · 2023-02-21T16:44:38Z

I'd prefer to wait for the S:K97T to show up outside of South Africa, as the sequence quality is not great and it could be an artefact. As soon as we see a few more high quality sequences let me know and I'll designate.

xz-keg · 2023-02-23T05:32:53Z

One more from Northern Ireland
EPI_ISL_16996428

xz-keg · 2023-02-24T18:21:33Z

130 seqs now.

It seems that branch 1 (XBB.1.5+S:K97T) is real, some of the additional branches are simply branch 1 but assigned to other branches due to having another common mutation with other XBB.1.5s. The branch is also detected in UK,US and Singapore.

But not sure about branch 2 as no more seqs coming from this branch.

AngieHinrichs · 2023-02-27T18:28:49Z

Ah that calls for branch specific masking 🙃 @AngieHinrichs

I added some branch-specific masking (ucscGenomeBrowser/kent@ac5d7c6). Let me know if you see a difference, and beware that recombinants placed in XBB might have some missing reversions due to the masking.

xz-keg · 2023-03-01T01:06:50Z

Ah that calls for branch specific masking 🙃 @AngieHinrichs

I added some branch-specific masking (ucscGenomeBrowser/kent@ac5d7c6). Let me know if you see a difference, and beware that recombinants placed in XBB might have some missing reversions due to the masking.

Yeah it works somehow and result in new branch arrangements.

new place for branch 2

However, there appears to be a new. branch with new flip-flop reversions (10 seqs)
a new branch

xz-keg · 2023-03-01T01:08:16Z

135 seqs now.

Under new arrangement it can be categorized. as

branch. 1: 108 seqs
branch 1
branch. 2: 4 seqs
branch 3: 7. seqs (I guess it shall be a sub-branch of branch 1 instead of sub-branch of C10369T)
branch 3
branch 4(Ord1a:G519S, Orf8:P36L): 1 seq (I guess like branch 3, it. shall also be a sub-branch of branch 1)
branch 4
branch 5(T22246C): 2seqs( like branch 3)
branch 5
branch 6: new branch with new flip-flop reversions

branch 7 (T10204C, or C4901T+T10204C) : 3 seqs(like branch 3)
branch 7

AngieHinrichs · 2023-03-01T01:18:16Z

However, it seems that the new arrangement is still not where it should be, with another flip-flop reversion...

new place for branch 2

Ah, thanks for pointing that out. That is a different type of problem: the branch seems to share A27038T, T27039A, C27040A with USA/NC-CORVASEQ-CLT-014136/2023 which was placed with A24730T and T27810C (ORF7b:F19L). But that branch doesn't have A24730T and T27810C so it gets reversions -- the 3 shared mutations are stronger than the 2 disagreeing mutations that require mutations. (Having 3 mutations in consecutive bases (27038-27040) is usually though not always a sign of sequencing errors.) I will see if I can clean that up by temporarily removing USA/NC-CORVASEQ-CLT-014136/2023 and reoptimizing.

xz-keg · 2023-03-09T00:26:47Z

177 seqs now, detected in Austria and England.

xz-keg · 2023-03-09T03:52:21Z

This one starts to show 14% growth advantage against XBB.1.5 in South Africa.

compare link

xz-keg · 2023-03-16T06:01:37Z

187 seqs now, one more country of Poland.

xz-keg · 2023-03-17T10:44:32Z

234 seqs now, spread to Ireland

M-J-Murray · 2023-04-26T09:38:24Z

This has been merged incorrectly into the lineage_notes.txt, instead of S:K97T, you have merged S:97T.

xz-keg changed the title ~~Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa~~ Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (One branch also have S:K444T and S:L452R） Feb 10, 2023

corneliusroemer added potential artefact Could be defined by artefact, should be investigated carefully before designation monitor currently too small, watch for future developments recombinant sublineage labels Feb 10, 2023

FedeGueli mentioned this issue Feb 10, 2023

XBB.1.5 spike diversity - multiple lineages issue to track easily if any spike mutation appears (and circulates) within XBB.1.5 lineage - Last update 12/03/2023 #1510

Closed

corneliusroemer self-assigned this Feb 21, 2023

xz-keg changed the title ~~Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (One branch also have S:K444T and S:L452R）~~ Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa, exported to Singapore and USA. Feb 22, 2023

xz-keg changed the title ~~Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa, exported to Singapore and USA.~~ Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (180 seqs, various countries) Mar 11, 2023

xz-keg changed the title ~~Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (180 seqs, various countries)~~ Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (187 seqs, various countries) Mar 16, 2023

xz-keg changed the title ~~Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (187 seqs, various countries)~~ Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially in South Africa but now in various countries) Mar 17, 2023

corneliusroemer closed this as completed in 3f39aba Mar 18, 2023

corneliusroemer added the designated label Mar 18, 2023

corneliusroemer added this to the XBB.1.5.25 milestone Mar 18, 2023

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Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially South Africa only but now in various countries, growth advantage inside South Africa against XBB.1.5) #1643

Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially South Africa only but now in various countries, growth advantage inside South Africa against XBB.1.5) #1643

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Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially South Africa only but now in various countries, growth advantage inside South Africa against XBB.1.5) #1643

Multiple branches of XBB.1.5(or XBB*+S:486P?) with S:K97T in South Africa (234 seqs, Initially South Africa only but now in various countries, growth advantage inside South Africa against XBB.1.5) #1643

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