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Eg.1 With a S:G1124V mutation (676 sequences in 29 countries) #1953

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Fearuncle opened this issue Apr 25, 2023 · 8 comments
Closed

Eg.1 With a S:G1124V mutation (676 sequences in 29 countries) #1953

Fearuncle opened this issue Apr 25, 2023 · 8 comments
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on hold on hold until parental issue resolved XBB proposed sublineage of XBB

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@Fearuncle
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Fearuncle commented Apr 25, 2023

Keep in Mind I'm a high school student that didn't study virology.
First sequenced January 3rd, The Top 3 countries are, Belgum (117), Luxemburg (76), France (49)
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@krosa1910
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Welcome to this community. Let me have some suggestions for you to provide better issues.
Look at issue #1 to propose a lineage, which means that specified origination, a possible mutation path and lists of sequence within your proposal. Currently this is done with Gisaid database easily. After making these Gisaid Inquiry we go to Usher to get a mutation tree that better visualize sequence relationship. (There are alternatives like augur or taxonium, but I think usher is easy to use)
Cov-spectrum is a great tool at calculating recent frequencies, and its pretty standard site to check advantages. You could also go to collection 24/42 to check if your lineage would really rank among top lineages.Example is the issue 1723 with sky-rocketing advantage, which later classify as xbb.1.16, and I am pretty sure you know its story. However, cov-spectrum usually is incomplete as its update of data from Gisaid is not too frequent, and it also does not show how you get a mutant. Thus, performing gisaid inquiry is a pretty standard way of doing things.

@krosa1910
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Wait, I remember that this is related with the G24933T mutation, that is highly ambiguous. So this could be an artefect . Cov-spectrum has this bad habit of classifying potential artefects like C44T and G21987A or else into their mutation tables.
@FedeGueli @corneliusroemer I am not very famaliar with classifying those, maybe you could judge.

@BorisUitham
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BorisUitham commented Apr 25, 2023

I have also been watching this one, I'm really unsure if this is an artefact or not. It does seem to have a logical spread: its mostly in the french part of belgium, luxembourg and france. there is also a clear growth pattern from 0 to 100% over time compared to eg.1* baseline when looking at the belgian sequences. that makes me think this is real (but even then maybe that does make it difficult for designation purposes if the mutation site occurs frequently outside this lineage as artefact)
However sadly i couldnt really find out if the phylogeny was logical in usher, since it automatically masks that mutation site meaning that the sequences appear all over the tree...

Edit: one clue that this might be real (i think) is when you look at its biggest branch, which has orf1ab:v4827i. if you look at just eg.1* + orf1ab:v4827i, you get 61 sequences on covspectrum of which 100% have s:g1124v. if it was a randomly occuring artefact, wouldnt it be less than 100%? The same goes for the secondary branch of orf1ab:P1497L which is also 100% s:g1124v

orf1ab:P1497L is nsp3:P697L which has 0.305 fitness in bloomlab mutation site fitness calculator
orf1ab:V4827I is nsp12:V435I which has -0.684 calculated fitness

Here is the usher tree (as a downsampled global tree), which does not take G1124V into account. I imagine if this is not an artefact, that in the real tree all these branches are connected to an intermediary node of G1124V
Screenshot_20230425-092932

The two biggest branches also have quite favourable growth advantage, and when designating you could theoretically ignore the s:g1124v as it is not needed in the search term.
The growth advantages of these branches correspond to the calculated bloomlab fitness of respectively +0.305 (above) and -0.684 (below)
EG.1* + orf1ab:P1497L:
Screenshot_20230425-093900

EG.1* + orf1ab:V4827I:
Screenshot_20230425-093927

@thomasppeacock thomasppeacock added the XBB proposed sublineage of XBB label Apr 26, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (226 sequences) Eg.1 With a S:G1124V mutation (235 sequences) Apr 28, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (235 sequences) Eg.1 With a S:G1124V mutation (258 sequences) Apr 29, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (258 sequences) Eg.1 With a S:G1124V mutation (266 sequences) May 2, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (266 sequences) Eg.1 With a S:G1124V mutation (266 sequences in 21 countries) May 2, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (266 sequences in 21 countries) Eg.1 With a S:G1124V mutation (298 sequences in 21 countries) May 4, 2023
@corneliusroemer
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corneliusroemer commented May 6, 2023

Good spot, I've also noticed these 1124V

Seems to be masked in the Usher tree. @AngieHinrichs can you confirm? What's the reason? It doesn't seem that homoplasic (anymore) - don't see why it would need to be masked in XBB. But maybe I'm missing something.

This would be impossible to track by Usher as long as the nuc mutation is masked, so need to put this on hold for now

@corneliusroemer corneliusroemer added the on hold on hold until parental issue resolved label May 6, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (298 sequences in 21 countries) Eg.1 With a S:G1124V mutation (310 sequences in 21 countries) May 6, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (310 sequences in 21 countries) Eg.1 With a S:G1124V mutation (330 sequences in 22 countries) May 12, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (330 sequences in 22 countries) Eg.1 With a S:G1124V mutation (363 sequences in 22 countries) May 13, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (363 sequences in 22 countries) Eg.1 With a S:G1124V mutation (373 sequences in 22 countries) May 15, 2023
@AngieHinrichs
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Seems to be masked in the Usher tree. @AngieHinrichs can you confirm? What's the reason? It doesn't seem that homoplasic (anymore) - don't see why it would need to be masked in XBB. But maybe I'm missing something.

It is in the Problematic Sites set:

MN908947.3      24933   .       G       K,T     .       mask    SUB=NDM,RCD;EXC=highly_ambiguous,highly_homoplasic,narrow_src;SRC_COUNTRY=Australia;SRC_LAB=VIDRL;GENE=gene-S;AA_POS=1124;AA_REF=G;AA_ALT=X,V

@BorisUitham
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I've seen that problematic sites, which is why I didn't continue making an issue with this before, but in this case it doesn't really seem like a standard artefact to me considering the "logical" high incidence with neighboring belgium, france and luxembourg. And of course i couldnt let usher make a nice tree because of the masking. Is there anything that would tip off that this isn't real?

@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (373 sequences in 22 countries) Eg.1 With a S:G1124V mutation (415 sequences in 23 countries) May 21, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (415 sequences in 23 countries) Eg.1 With a S:G1124V mutation (429 sequences in 23 countries) May 22, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (429 sequences in 23 countries) Eg.1 With a S:G1124V mutation (475 sequences in 23 countries) May 30, 2023
@Fearuncle
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image
orf1ab:P1497L got s:K478R 11 seq.

@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (475 sequences in 23 countries) Eg.1 With a S:G1124V mutation (582 sequences in 23 countries) Jun 10, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (582 sequences in 23 countries) Eg.1 With a S:G1124V mutation (582 sequences in 27 countries) Jun 10, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (582 sequences in 27 countries) Eg.1 With a S:G1124V mutation (625 sequences in 29 countries) Jun 20, 2023
@Fearuncle Fearuncle changed the title Eg.1 With a S:G1124V mutation (625 sequences in 29 countries) Eg.1 With a S:G1124V mutation (676 sequences in 29 countries) Jul 1, 2023
@FedeGueli
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image orf1ab:P1497L got s:K478R 11 seq.

did this one went on growing?

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