Private channel session 863
39 messages over 1h 49m, 2021-01-23 – 2021-01-23.
A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.
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spike L18F is seen in 310 genomes within B.1.1.7 in the UK - more convergence
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For fuck sake! This is adding immune escape to the increased transmission. Just need to add E484K and L417N/T and we're good to go.
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Here is a full list of variants in B.1.1.7 on sites with mutation seen in P.1 and B.1.351 (and not originally in B.1.1.7):```Gene Mutation Original lineage Seen in B.1.1.7ORF1ab S1188L P.1 A/L/P 1/4/2 genomesK1655N B.1.351 M/N 1/3 genomesE5665D P.1 D 2 genomes spike L18F P.1/B.1.351 L 310 genomesT20I P.1 N 17 genomesP26S P.1 H/L/S 1/2/5 genomesD80A B.1.351 Y 4 genomesD138Y P.1 G/H 1/75 genomesR190S P.1 M/S 2/2 genomesD215G B.1.351 B/N/Y 1/1/8R246I B.1.351 K 4 genomesE484K P.1/B.1.351 G/K 1/10 genomesH655Y P.1 Y 7 genomesP681R R 10 genomesA701V B.1.351 V 25 genomesE P71L B.1.351 H/L/S 3/5/2N P80R P.1 L 6 genomesT205I B.1.351 I/N 13/2 genomes```
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Probably some of them (particularly those with multiple residues) are probably just plastic.
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Will need to see how often some of these occur outside the background of B.1.1.7
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Yeah. Very interesting to see how several of these are shared with BRA/RSA variants though - I find that a little confusing
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I thought the mutations observed in P.1 / B.1.351 were likely fixed in a single individual and then took off in the population. But seeing them pop up here suggest to me that that likely wasn't the case. Maybe immune selection in_the population_, not _intrahost_, actually fixed them in the first place.
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I think the UK lineage is likely a weird example of a chronic infection that took off, while the BRA/RSA lineages are just a result of selection on the population.
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The plastic ones could have just been hitchhiking in the generating individual
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True
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Trevor has been going around saying the RSA lineage arose in sequence based on some genomes with only some of the mutations but they are not old sequences and I have heard that Tulio uses some weird homebrew bioinformatics that may call for reference occasionally.
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Eh?
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Exactly
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That's weird. I mean, P.1. has many overlapping mutations so surely those at least must be right?
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I thought they were more likely reversions than intermediates (still unlikely) but when I pointed them out to Tulio hesaid he thought they weren't real and they were fixing them.
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Oh.
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I still think all three are chronic cases which have selected for antigenic escape within the host (and for B.1.1.7 atleast increased transmissibility) and then these turned out to be in places where these were very fit.
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Otherwise we would see these combinations coming up a lot.
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Yeah, that's true - either strong bottleneck (in single host) or very strong selection.
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Not to say they couldn't given enough time but the chronic patient is just a kickstart
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Such an interesting virus evolutionarily speaking - I _do_ wonder what other shit it'll throw after us.
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Tulio and his tools.
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There was a reason we developed more robust tools...
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But as always - any one of these tools used in the wrong hands > disaster.
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Yeah, he is using the ARTIC protocol on Illumina but then some crazy semi commercial software called Genome Detective
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Which seems to be a web app with a 'premium' pay-for version. Tulio was involved in development which is probably why.
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I remember I came across that - I think maybe even reviewing a paper with it. Really need to use iVar if he's on theIllumina platform.
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I have mentioned it to him.
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Don't like this - L18F has cropped up quite a few times in B.1.1.7 but most of the 310 are in a single large cluster inone area of the country
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Andrew alluded to it and I agree it's true - some spots on the genome are "slippery" or prone to mutation. It's the variable and constant domain meme of HIV, fle etc. In one sense hopeful since it suggests that while the space for mutation/adaptation is large it's not infinite. As @Andrew Rambaut referenced a handful ofimmunosuppressed/cancer patients out there (two NEJM paper) with patients with overlapping or common mutation/deletions, a few of which actually flip back and forth in the "quasispecies.' The strongly immunosuppressed/persistent patients interesting - KGA aware of one of ours at Tulane that has stayed PCR positive for over 8 months. No provirus and a rudimentary proofing mechanism but still as Emma Hodcraft said aplayground for the virus.
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Got to go to bed and stop staring at mutations.
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Yes but I really don't want to think about the blissfully ignorant mess we'd be in if YOU hadn't been staring atmutations over the past several months.
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Bob, you used the Q word.
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Oh oh.
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Spent HOURS putting the GIPA together...kind of hoping that the 'grand wizard of EgoHealth' makes into the public domain
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That'd be fun.
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Key question here - in an area of high standing immunity or low?
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@Eddie Holmes moment of weakness :scream_cat:
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@Eddie Holmes Don't worry - won't be part of the GIPA so your dirty secret is safe.