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mkedwards avatar mkedwards commented on August 30, 2024

(I realize that my ask around fixing indel handling is capital-H-Hard (TM). But maybe it's worth looking into adding Divvier (https://europepmc.org/article/pmc/pmc6933875) or a comparable MSA-twiddling pass into the Nextstrain pipeline.)

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rambaut avatar rambaut commented on August 30, 2024

I agree that 'undeletions' will not happen as a simple 'reinsertion' but it is possible for this happen through recombination with another virus in a co-infection. We have seen this already in the UK with some B.1.1.7 derived variants that have 'undeleted' the nsp12 deletion through recombination with other lineages: https://virological.org/t/658

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rambaut avatar rambaut commented on August 30, 2024

Will take a look and see if recombination is a plausible explanation for this.

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rambaut avatar rambaut commented on August 30, 2024

One other point - the deletion that causes SGTF marker is the 69-70 deletion which is in the middle of the s gene probe for these tests.

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rambaut avatar rambaut commented on August 30, 2024

In the example genome I looked at the 69-70 deletion is probably there but been replaced with Ns:

image

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rambaut avatar rambaut commented on August 30, 2024

Michigan Department of Health and Human Services seems to be really struggling to sequence and call the consensus at the spike 144 location (also the other deletions) where as the CDC doesn't. I suspect this may be an issue with the bioinformatics pipelines being used:
image

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rambaut avatar rambaut commented on August 30, 2024

This is also the case for the nsp6 deletion:
image

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rambaut avatar rambaut commented on August 30, 2024

Closing this issue because it is not directly related to lineage proposals.

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mkedwards avatar mkedwards commented on August 30, 2024

Thanks for digging into the raw data. I agree that there are signs here of a sequence calling problem in one lab. I'm aware that it's not the Δ69–70 SGTF that's at risk; I was concerned about attempts to discriminate among B.1.1.7/B.1.351/P.1 using Δ143–144 and/or the ORF1a Δ3675–3677 screen mentioned in https://twitter.com/nathangrubaugh/status/1353710736124633090.

I am skeptical about the recombination arguments but parsimony says they don't need debating here. 😃

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