JG.4/DV.7.1 recombinant(4 seqs) and XCT: its further recombinant with XBB.1.9.2 #811

xz-keg · 2023-09-14T02:28:05Z

I find a EG.5.1.3/DV.7.1 recombinant that usher registers with too many reversions and may be dropped out.

EG.5.1.3--DV.7.1
Breakpoint: Between 18584 and 19325

Extra mutations: C1684T,C7051T,C20320T,T24073C

Orf1b:H2285Y

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?nucMutations=C24134A%2CC7051T%2CC1889T&nextcladePangoLineage1=EG.5.1.3*&nextcladePangoLineage2=DV.7.1*&analysisMode=CompareEquals&

C1684T,C7051T from an EG.5.1.3-branch.

C20320T,T24073C are private

Some DV.7.1 branches have C20320T however they have additional mutations after that so not possible.

Query: C24134A,C7051T,C1889T

The branch include 2 recombs:

(this one with additional C29546T, private, no DV.7.1 has this)
EG.5.1.3--DV.7.1
For EPI_ISL_18254485(France), C24134A,C7051T,C1889T,C29546T

(this one with additional A27507C, T28297C, G27915T(Orf9b:I5T, Orf8:G8*), indicating 2nd breakpoint between 26276 and 27506
EG.5.1.3--DV.7.1--XBB.1.9.2? (Not EG.5.1.3 for not having C29625T)
3-seq branch: C24134A,C7051T,C1889T,A27507C (USA, Switzerland)

So EG.5.1.3 recombs with DV.7.1 and get recomb 1, while recomb 1 recombs with another XBB.1.9.2 and gets recomb 2?

If that's 1 seq I'll view it as artefact, however now we have 4 seqs from 3 countries.

EG.5.1.3-side donor:

Current usher

usher

AngieHinrichs · 2023-09-14T04:03:54Z

Added to list, should be added when 2023-09-14 build is done, thanks.

xz-keg · 2023-09-26T07:45:21Z

@AngieHinrichs

There is a second seq near this . EPI_ISL_18284092 It is a sandwich recombinant of EG.5.1--DV.7.1--EG.5.1, also being removed by usher.

xz-keg · 2023-09-26T07:46:13Z

usher

AngieHinrichs · 2023-09-27T16:29:19Z

Thanks @aviczhl2, I added EPI_ISL_18284092 to the list so it should be added in the 2023-09-28 build, sorry about the delay. EPI_ISL_18254485 is being added to the tree daily, but then removed by our filter of max 20 private mutations on a singleton sequence. When EPI_ISL_18284092 is added, then EPI_ISL_18254485 will no longer be a singleton with all those mutations and the two sequences should be retained in the 2023-09-28 tree.

xz-keg · 2023-09-28T06:50:36Z

@AngieHinrichs A 3rd one appears, EPI_ISL_18316684, seems to be the same sandwich recomb of EPI_ISL_18284092.

AngieHinrichs · 2023-09-29T01:22:01Z

OK, added, should be in the 2023-09-29 build. ~~I don't see EPI_ISL_18284092 in the 2023-09-28 build (on dev.usher.bio) as expected; I will try to figure out what happened there.~~[Edit: I was looking at the wrong tree, never mind, USA/NY-GBW-H10-017-9117/2023|EPI_ISL_18284092|2023-09-07 and France/GES-IPP17866/2023|EPI_ISL_18254485|2023-08-28 are in the 2023-09-28 tree.]

xz-keg · 2023-09-30T14:38:21Z

@AngieHinrichs There's one more from Switzerland. EPI_ISL_18327700

usher

xz-keg · 2023-09-30T15:31:07Z

@FedeGueli @ryhisner @NkRMnZr @krosa1910 @HynnSpylor please help me on this. Seems extremely complex.

FedeGueli · 2023-09-30T19:22:57Z

@FedeGueli @ryhisner @NkRMnZr @krosa1910 @HynnSpylor please help me on this. Seems extremely complex.

For sure inwill look at it tomorrow

AngieHinrichs · 2023-10-01T04:51:24Z

Added, thanks.

FedeGueli · 2023-10-01T09:45:50Z

It is looks like a XCM-alike sandwich recombinant between EG.5.1.3/DV.7.1 ( and the french sample could be a further recombination or a recombinant itself parent of this recombinant)

to me it could be (please check):
from Eg.5.1.3:
C1889T,C2334T,G5720A,C9693T,C12789T,T16342C,A16878T,A18492G,A27507C,G27915T,T28297C

from DV.7.1: A19886G,A20741G,T22016C,C22033A,A22115G,A22190G,T22200G,G22331A,A22893C,T22917G,G22927T,T22928C,C24134A,T24991A,G25606A,C25721T,T25959C
and C20320T sublineage of DV.7.1 (10 seqs)

Private mutations:
C44T,C835T,C1684T,C7051T ,T24073C

So it would be

1-18429 EG.5.13
18430-19885 Breakpoint 1
19886-25959: DV.7.1
25960-27506 : Breakpoint 2
27507- 3' end: EG.5.1.3

xz-keg · 2023-10-01T10:18:18Z

So it would be

1-18429 EG.5.13 18430-19885 Breakpoint 1 19886-25959: DV.7.1 25960-27506 : Breakpoint 2 27507- 3' end: EG.5.1.3

Thanks for the analysis. As said this is a complex recomb so there're some problems need fixing.

How about 29625 missing? This one doesn't have C29625T however EG.5.1.3 has.

Also that DV.7.1 branch of C20320T has additional C27849A which is not present in the French seq (where 19886-3' are all DV.7.1)

FedeGueli · 2023-10-01T13:09:01Z

27849

yeah it could be also this one as donor: https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_3e515_96edd0.json?c=userOrOld&label=id:node_10941447 (link edited)

xz-keg · 2023-10-01T13:12:11Z

27849

yeah it could be also this one as donor: https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_3e515_96edd0.json?c=userOrOld&label=id:node_10941447 (link edited)

But it also doesn't have 28695?

FedeGueli · 2023-10-01T13:12:54Z

Yeah about the orf10 mutation likely the donor was already itself a recombinant within XBB.1.9 family.

FedeGueli · 2023-10-01T13:13:43Z

27849

yeah it could be also this one as donor: https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_3e515_96edd0.json?c=userOrOld&label=id:node_10941447 (link edited)

But it also doesn't have 28695?

it is dv.7.1 : i mean DV.7.1 side donor

FedeGueli · 2023-10-01T13:16:47Z

So concluding:
it could be a EG.5.1.3 with a dv.7.1/xbb.1.9 recombinant
or a "EG.5.1.3/XBB.1.9 recombinant"sandwich recombinant with DV.7.1

JosetteSchoenma · 2023-10-15T16:54:47Z

XCT

FedeGueli · 2023-10-15T22:08:25Z

Designated XCT

xz-keg · 2023-10-16T11:07:18Z

It seems that currently the parental recomb (without G8*, C27507A and T28297C) is designated as XCT?

https://nextstrain.org/staging/nextclade/sars-cov-2

FedeGueli · 2023-10-16T11:58:51Z

It seems that currently the parental recomb (without G8*, C27507A and T28297C) is designated as XCT?

https://nextstrain.org/staging/nextclade/sars-cov-2

only that one? does the designation misses the real XCT? in the other case it catches all i would not make a difference cc @corneliusroemer what do you think?

xz-keg · 2023-10-16T13:39:50Z

only that one? does the designation misses the real XCT? in the other case it catches all i would not make a difference cc @corneliusroemer what do you think?

I'm not sure, but the 2 recombs shall not be under one name. Either give both a designation, this may create a recomb with only 2 seqs but helpful for explanation. Or remove seqs of the parental recomb from XCT and to clarify the children recomb is XCT.

xz-keg · 2023-10-17T04:15:58Z

@AngieHinrichs new XCT(children recomb) seqs,

EPI_ISL_18395595, EPI_ISL_18392290, EPI_ISL_18391834, EPI_ISL_18381777,EPI_ISL_18391799

xz-keg · 2023-10-19T10:47:54Z

@AngieHinrichs 7 more today, all children recomb

EPI_ISL_18403312, EPI_ISL_18403342, EPI_ISL_18403373-18403374,
EPI_ISL_18405163, EPI_ISL_18406342, EPI_ISL_18406427,

JosetteSchoenma · 2023-10-20T11:29:43Z

2 more from NSW. EPI_ISL_18411444 and EPI_ISL_18411775
The query catches 33 samples now!

AngieHinrichs · 2023-10-20T23:34:34Z

Thanks @aviczhl2 and @JosetteSchoenma, I added those IDs to my file. In the future would it be too much trouble for you to add sequences to https://github.com/sars-cov-2-variants/lineage-proposals/blob/main/recombinants.tsv ?

xz-keg · 2023-10-21T03:14:25Z

Thanks @aviczhl2 and @JosetteSchoenma, I added those IDs to my file. In the future would it be too much trouble for you to add sequences to https://github.com/sars-cov-2-variants/lineage-proposals/blob/main/recombinants.tsv ?

That's for undesignated lineages.

Will it cause conflict for designated lineages as they may also appear elsewhere with different labels?

recombinants.tsv also has a function for manual search of currently proposed recombs I think it shouldn't be too big (keep it <1000
seqs). Designated lineages may grow to very large and if there's too many seqs inside we cannot manual search.

What's your suggestion?

AngieHinrichs · 2023-10-23T14:24:59Z

OK, I misunderstood the purpose of recombinants.tsv, thanks for clarifying that.

Perhaps there could be a separate file just for IDs of sequences that should be exempted from the too-many-reversions filter? Like #991, but just a file of IDs.

xz-keg · 2023-10-23T17:56:27Z

OK, I misunderstood the purpose of recombinants.tsv, thanks for clarifying that.

Perhaps there could be a separate file just for IDs of sequences that should be exempted from the too-many-reversions filter? Like #991, but just a file of IDs.

Maybe I shall create one to include those seqs as well as XCT before they are not removed by usher.

BTW: Is XCM still being filtered out? When can usher automatically recognize a lineage and stop removing its seqs?

AngieHinrichs · 2023-10-24T17:27:41Z

Maybe I shall create one to include those seqs as well as XCT before they are not removed by usher.

That would be extremely helpful!

BTW: Is XCM still being filtered out?

Most XCM should not be filtered out as far as I can tell. The 2023-10-23 tree has 72 sequences placed in XCM even though my local file that exempts sequences from too-many-reversion filtering has only 7 IDs (none in recombinants.tsv). They are right on the edge of filtering, with 5 reversions relative to placement in the nextclade tree version 2023-09-21T12:00:00Z. Any sequence with one or more extra reversions could be filtered.

When can usher automatically recognize a lineage and stop removing its seqs?

When these things happen:

There is a nextclade sars-cov-2 data release
I re-run nextclade with the latest data on all sequences

xz-keg · 2023-10-25T02:58:34Z

There is a nextclade sars-cov-2 data release

I re-run nextclade with the latest data on all sequences

By nextclade data release, do you mean https://nextstrain.org/staging/nextclade/sars-cov-2 ?

I see XCT is already there?

AngieHinrichs · 2023-10-25T04:46:10Z

I believe https://nextstrain.org/staging/nextclade/sars-cov-2 is Cornelius's nightly build -- it's pre-release. By release I mean official releases like https://github.com/nextstrain/nextclade_data/releases/ . When there is a new release, I can download the new release data files and then re-run nextclade on all sequences.

My nightly build runs the latest downloaded release on all new sequences, which doesn't take much time -- but re-running nextclade every night on all pre-existing sequences would take a lot more time.

xz-keg · 2023-10-25T07:01:10Z

I believe https://nextstrain.org/staging/nextclade/sars-cov-2 is Cornelius's nightly build -- it's pre-release. By release I mean official releases like https://github.com/nextstrain/nextclade_data/releases/ . When there is a new release, I can download the new release data files and then re-run nextclade on all sequences.

My nightly build runs the latest downloaded release on all new sequences, which doesn't take much time -- but re-running nextclade every night on all pre-existing sequences would take a lot more time.

I see. So whatsoever designated lineages will be included eventually when nextclade performs a formal release every month?

AngieHinrichs · 2023-10-25T16:39:08Z

I see. So whatsoever designated lineages will be included eventually when nextclade performs a formal release every month?

Yes.

xz-keg · 2023-11-12T01:29:36Z

1 more for the parental recomb. EPI_ISL_18494770

xz-keg · 2023-11-19T01:42:06Z

1 more for the parental recomb EPI_ISL_18518466

FedeGueli added recombinant Singlet One only sample. FLip = S:L455F / S:F456L labels Sep 14, 2023

xz-keg changed the title ~~EG.5.1/DV.7.1 recombinant that may be dropped out by usher~~ EG.5.1/DV.7.1 recombinant that may be dropped out by usher (2 seqs, 2 countries) Sep 26, 2023

xz-keg changed the title ~~EG.5.1/DV.7.1 recombinant that may be dropped out by usher (2 seqs, 2 countries)~~ 2 EG.5.1/DV.7.1 recombinants that may be dropped out by usher Sep 26, 2023

xz-keg changed the title ~~2 EG.5.1/DV.7.1 recombinants that may be dropped out by usher~~ 3 EG.5.1/DV.7.1 recombinants that may be dropped out by usher Sep 28, 2023

FedeGueli mentioned this issue Sep 28, 2023

2 Weird Flip Sequences with C7051T and seemingly a lot of similar CT transitions #878

Closed

xz-keg mentioned this issue Sep 30, 2023

Suggestion to update removal rules to adapt to the current mass recombinant situation yatisht/usher#352

Open

xz-keg changed the title ~~3 EG.5.1/DV.7.1 recombinants that may be dropped out by usher~~ EG.5.1/DV.7.1 recombinants that may be dropped out by usher(4 seqs, 3 countries) Sep 30, 2023

xz-keg changed the title ~~EG.5.1/DV.7.1 recombinants that may be dropped out by usher(4 seqs, 3 countries)~~ 2 EG.5.1/DV.7.1 recombinants that may be dropped out by usher(3 seqs and 1 seq) Sep 30, 2023

xz-keg changed the title ~~2 EG.5.1/DV.7.1 recombinants that may be dropped out by usher(3 seqs and 1 seq)~~ 2 EG.5.1/DV.7.1(/XBB.1.9.2?) recombinants that may be dropped out by usher(3 seqs and 1 seq) Sep 30, 2023

xz-keg changed the title ~~2 EG.5.1/DV.7.1(/XBB.1.9.2?) recombinants that may be dropped out by usher(3 seqs and 1 seq)~~ EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(1 seqs and 3 seq) Sep 30, 2023

xz-keg changed the title ~~EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(1 seqs and 3 seq)~~ EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(1 seq and 3 seqs) Sep 30, 2023

FedeGueli added designated and removed To be proposed Green light for proposal labels Oct 15, 2023

FedeGueli added this to the XCT milestone Oct 15, 2023

FedeGueli added XCT and removed Rapid review needed Singlet One only sample. labels Oct 15, 2023

xz-keg changed the title ~~EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(2 seq and 16 seqs )~~ XCT: EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(2 seq and 16 seqs ) Oct 16, 2023

FedeGueli referenced this issue in cov-lineages/pango-designation Oct 19, 2023

Remove two XCT designations that are possibly a different lineage

36aee64

xz-keg mentioned this issue Oct 22, 2023

Issue to Register Singlet Recombinants that shall be not be removed by usher ( Until 2024-7-2 ) [Part I] #991

Closed

xz-keg changed the title ~~XCT: EG.5.1.3/DV.7.1 recombinant and its further recombinant with XBB.1.9.2 that may be dropped out by usher(2 seq and 16 seqs )~~ JG.4/DV.7.1 recombinant(4 seqs) and XCT: its further recombinant with XBB.1.9.2 Nov 19, 2023

JG.4/DV.7.1 recombinant(4 seqs) and XCT: its further recombinant with XBB.1.9.2 #811

JG.4/DV.7.1 recombinant(4 seqs) and XCT: its further recombinant with XBB.1.9.2 #811

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