Multiple BA.2 sublineages circulating in India: proposal for a fast designation of them to track efficiently emerging sublineages there

[FedeGueli]

((Edited 6/7)): I wrote down uncorrectly the S: 248 mutations mentioned below (now corrected) they are S:Y248S and S:Y248N , sorry everyone for this silly mistake. thx @josetteshoenma for spotting it))

Following the ongoing discussion in #773 "BA.2.75" issue
and the need expressed by @karyakarte to have BA.2 sublineages quickly designated to track them efficiently
and the important comment by @silcn:
"Regarding BA.2 lineages in India: Japan just uploaded 42 sequences from travellers from India, sampled from 27 May to 16 June, which might give a more representative sample given the differences in sequencing quantity across India. Here is the lineage breakdown according to Usher:

17 BA.2.38 (of which 1 is #809)
15 BA.2 (of which 8 are #787, 2 have S:L452M but are not BA.2.56, and 1 has S:R346T+S:L452M but is not BA.2.74)
4 BA.2.56
2 BA.2.74
1 BA.2.75
1 miscellaneous BA.1/BA.2 recombinant
1 BA.4
1 BA.5.2

I agree with the comments in that thread that there is a very strong case for designating #787.

Originally posted by @silcn in #773 (comment) "

Here i ask to designate the indian BA.2 sublineages already proposed in:
(Edited now #809 has been designated BA.2.38.1
#809 = BA.2.38 + S:444N + S:247N + S:Y248S)
#746 = BA.2.38+T7153C+S:K147E, S:K444N, S:I692L, S:417T+ORF1b:D51N
#762 = BA.2.10 S: T22N, S:L368I, S:N969R
Edited
#787 = BA.2+S:346T+S:Y248N now designated BA.2.76

Plus i ask to designate the following unproposed ones (see in the complete sheet here):
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Lineages	Query x Growth adv	Week Growth Adv	Query for sequences	Nr of Seqs	country	Issue	designation status	Author	Usher tree
BA.2.38+T7153C+S:444N+ORF1a:N3725S+orf1a:T1543I+C17373T+orf1a:T4355I+S:157S		cluster	https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3A444N%2CORF1a%3AN3725S%2Corf1a%3AT1543I%2Corf1a%3AT4355I%2CS%3A157S&nucMutations=T7153C%2CC17373T&	15	India		Unproposed	Sakaguchi	https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_18b9b_ef0ab0.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:C4893T,A11439G
BA.2.38+S:417T+C21622T+S:71F, S:478R,	https://cov-spectrum.org/explore/World/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A417T%2CS%3A71F%2CS%3A478R&analysisMode=CompareToBaseline&	-34%	https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3A478R%2CS%3A71F&aaMutations1=ORF1a%3A556K%2CN%3AP364L%2CORF1a%3AD930N%2CORF1a%3AP3504L%2CN%3A136&nucMutations1=A11782G%2C12160A&	70	India		Unproposed	Zach	https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_5c74_eee6e0.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:C21622T
BA.2+K3353R+S:452M+0rf10:24L (G29628T)	https://cov-spectrum.org/explore/World/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A452M&nucMutations1=G29628T&analysisMode=CompareToBaseline&	-38%	https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3A452M&nucMutations=G29628T&aaMutations1=S%3A452M&nucMutations1=G29628T&	147	India		Unproposed	Fede	https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_38a02_f02a90.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:G29628T
BA.2+29628T + S:452M	https://cov-spectrum.org/explore/India/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A452M&nucMutations1=29628T&analysisMode=CompareToBaseline&	-52%	https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3A452M&nucMutations=29628T&	104	India		Unproposed	Fede	https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_380f2_f02710.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:G29628T

[FedeGueli]

One more potentially interesting found by @Sinickle

Lineages	Query x Growth adv	Week Growth Adv	Query for sequences	Nr of Seqs	country	Issue	designation status	Author	Usher tree
BA.2.38 + S:346T+ orf1a:3763FI+C26942T	https://cov-spectrum.org/explore/India/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A417T%2CS%3A346T&nucMutations1=26942T&analysisMode=CompareToBaseline&	-45%	https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?aaMutations=S%3A346T%2CS%3A417T%2COrf1a%3A3763F&nucMutations=26942T&	30	India		Unproposed	Nick	https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice2_genome_bfe4_fa21b0.json?branchLabel=aa%20mutations&c=pango_lineage_usher&label=nuc%20mutations:G8653C,C26942T

https://docs.google.com/spreadsheets/d/1zKF3PKaosF3OCcW54gWkyV7Spz8uWrCsYef9IHbj7FA/edit?usp=drivesdk

it is just 30 sequences but 13 out of 30 have S:483A beyond S:346T.

[FedeGueli]

I have added a new sheet to the first one with prevalences of main indian BA.2 sublineages region by region HERE

It seems that it is a team work for fast BA.2 sublineages in keeping BA.5 at the corner. This could mean they are really trasmissible as BA.5 but also that some growth advantage estimated just on India with CovSpectrum could be artificially high.

@corneliusroemer @thomaspeacock @chrisruis @AngieHinrichs

[FedeGueli]

Another sublineage appears to being growing fast in India it is a branch of the one proposed by @c19850727 in #812
it is defined by:
S:450D + S:Y248S
then
orf1a:2016I +orf1b:1416V
It reached 28 seqs from 6 less than one week ago.
and this sublineage has been detected in Singapore, Australia, Israel one sequence each that gives me the idea of travel related samples
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_42338_46cdd0.json?branchLabel=aa%20mutations&c=country&label=nuc%20mutations:C6312T

[FedeGueli]

Updated list below, cc @chrisruis @corneliusroemer @karyakarte
It remains to designate just the indian sublineage of #812 that shows growth advantage versus BA.5

here:

BA.2.75( S:K147E, S:W152R, S:F157L, S.I210V, S:G257S, S:D339H, S:G446S, S:N460K, S:R493Q	https://cov-spectrum.org/explore/India/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A339H%2CS%3A460K%2CE%3A11A&analysisMode=CompareToBaseline&	750,00%
BA.2.38.1 (S:K444N + S:S247N + S:Y248S)	https://cov-spectrum.org/explore/India/AllSamples/Past1M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=s%3A248s%2Cs%3A247n%2Cs%3A417t%2Cs%3A444n&pangoLineage1=ba.2*&analysisMode=CompareToBaseline&	312%
BA.2+ S:N450D + S:Y248S+orf1a:T2016I +orf1b:1416V+C16887T	https://cov-spectrum.org/explore/India/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A450D%2CS%3A248S%2Corf1a%3A2016I%2Corf1b%3A1416V&nucMutations1=C16887T&analysisMode=CompareToBaseline&	38%
BA.2.74+(14925T+C538T+S:R346T+S:L452M)	https://cov-spectrum.org/explore/India/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&variantQuery1=+S%3A346T+%26+NextcladePangoLineage%3ABA.2*+%26+S%3A452M&analysisMode=CompareToBaseline&	46%
BA.2.76 (S:R346T+S:Y248N)	https://cov-spectrum.org/explore/India/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A346T%2CS%3AY248N&pangoLineage1=BA.2&analysisMode=CompareToBaseline&	6%

BA.2.75( S:K147E, S:W152R, S:F157L, S.I210V, S:G257S, S:D339H, S:G446S, S:N460K, S:R493Q https://cov-spectrum.org/explore/India/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A339H%2CS%3A460K%2CE%3A11A&analysisMode=CompareToBaseline& 750,00%
BA.2.38.1 ( S:K444N + S:S247N + S:Y248S ) https://cov-spectrum.org/explore/India/AllSamples/Past1M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=s%3A248s%2Cs%3A247n%2Cs%3A417t%2Cs%3A444n&pangoLineage1=ba.2*&analysisMode=CompareToBaseline& 312%
S:N450D + S:Y248S+orf1a:T2016I +orf1b:1416V+C16887T https://cov-spectrum.org/explore/India/AllSamples/Past2M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A450D%2CS%3A248S%2Corf1a%3A2016I%2Corf1b%3A1416V&nucMutations1=C16887T&analysisMode=CompareToBaseline& 38%
BA.2.74+(14925T+C538T+S:R346T+S:L452M) https://cov-spectrum.org/explore/India/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&variantQuery1=+S%3A346T+%26+NextcladePangoLineage%3ABA.2*+%26+S%3A452M&analysisMode=CompareToBaseline& 46%
BA.2.76 (S:R346T+S:Y248N) https://cov-spectrum.org/explore/India/AllSamples/Past3M/variants?aaMutations=M%3A3N&nucMutations=12160A&aaMutations1=S%3A346T%2CS%3AY248N&pangoLineage1=BA.2&analysisMode=CompareToBaseline& 6%
https://docs.google.com/spreadsheets/d/1zKF3PKaosF3OCcW54gWkyV7Spz8uWrCsYef9IHbj7FA/edit?usp=drivesdk

[chrisruis]

Thanks everyone for the great work with these

This is what I'm seeing, running through the clades in the order they appear in the comments from @FedeGueli above:
Clade in #809
Is exhibiting signs of consistent growth as a proportion of BA.2.38/BA.2/Omicron sequences in India (covSpectrum as a proportion of BA.2.38 in India). Has been exported multiple times. It's still quite early but I think worth designating - now added as BA.2.38.1 to start on the branch with G22302A (S:S247N) and A22305C (S:Y248S)

Clade in #746
Clade within BA.2.38, doesn't appear to be growing as a proportion of BA.2.38 sequences in India:

Similar picture when moving back in the tree to incorporate deeper branches. Has been identified in multiple regions but without evidence of increasing as a proportion of BA.2.38 in any region from what I can see. So this one probably doesn't warrant a designation at this stage

Clade in #762
All of the current sequences within this clade were collected from Tamil Nadu between 28th May and 3rd June. There's not any more recent sequences from this clade from what I can see, despite 775 sequences from Tamil Nadu collected in June. This could be consistent with a single outbreak, as also mentioned in the #762. So I don't think we want to designate this clade at this stage

BA.2.38+T7153C+S:444N+ORF1a:N3725S+orf1a:T1543I+C17373T+orf1a:T4355I+S:157S clade
May have just started to increase as a proportion of BA.2.38 in India but jumps up and down so still very early - let's monitor this one and see what it looks like in the coming days

BA.2.38+S:417T+C21622T+S:71F+S:478R clade
Not currently evidence of increasing as a proportion of BA.2.38/BA.2/Omicron sequences in India:

Has reached reasonable frequency within some regions at some points but without a clear pattern of increasing. So this one probably doesn't warrant a designation at this stage

BA.2+K3353R+S:452M+0rf10:24L (G29628T) clade
Has stayed as quite a low proportion of BA.2 in India without evidence of increasing through time. However, looking at this in the UShER tree, this clade shows some geographical focus in India so we can designate based on that. We've added this as BA.2.78 to start on the branch with G29628T (Orf10:R24L). This mutation is quite near the end of the genome but almost all sequences also have C22916A (S:L452M)

BA.2+29628T + S:452M clade
Same as BA.2+K3353R+S:452M+0rf10:24L (G29628T) clade above (now BA.2.78)?

BA.2.38 + S:346T+ orf1a:3763FI+C26942T clade
Not seeing evidence of this one increasing as a proportion of BA.2.38/BA.2/Omicron in India:

So don't think this one warrants a designation at this stage

Subclade within the clade from #812
These sequences exhibit a clear epidemiological event through introduction(s) into India. We've therefore added this as BA.2.79.1 to start on the branch with C6312T (Orf1a:T2016I)

Happy to have another look if anything changes with these. Thanks again

@FedeGueli It might be easiest to close this issue and open a new issue for the BA.2.38+T7153C+S:444N+ORF1a:N3725S+orf1a:T1543I+C17373T+orf1a:T4355I+S:157S clade as this issue has a lot of information in it now

[FedeGueli]

Thank you very much @chrisruis for your very accurate work! I agree with everything stated by you above so:

1. i will open up an issue for the BA.2.38+(XXX)+S:157S one and i'll keep monitored
2. i will keep updated the New BA.2.38 sublineage with S:444N, S:147E, S:692L (350 seqs as of 2022-08-10, mostly India) #746 to see if the picture will become clearer (i suspect that it has reached a significant prevalence somewhere in India, but still probably without a strong growth advantage vs BA.2.38 baseline.
3. I'll keep monitored the S:478R and if it will reach a consistent count of sequences i'll propose it.
4. I'll keep an eye on the tree of the undesignated lineage with S:346T, as we have seen in BA.2.74 and BA.2.76 , one additional mutation could potentially boost its trasmissibility.

Thank you again.

[chrisruis]

Thanks @FedeGueli Sounds good

[FedeGueli]

@chrisruis i ushered the sublineage mentioned above with S:478R ( to name it quickly) it reached 108 Sequences and
@c19850727 spotted a well clustered sublineage of it carrying S:1264L that reached 16 sequences with three exportations one to Japan and one each to Canada and US.

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_242d8_dfc7e0.json?branchLabel=aa%20mutations&c=country&label=nuc%20mutations:C21622T

But what push me to re-open this issue and to designate the BA.2.38 (S:417T) sublineage with C21622T, S:69/70Del, S:S71F, S:T478R is that in the branch with S:1264L two sequences have popped up with S:452Q and S:446S beyond ORF1a:F1214I and nuc: C18744T

cc @AngieHinrichs @InfrPopGen @corneliusroemer @thomaspeacock