Private channel session 653
98 messages over 7h 1m, 2020-12-06 – 2020-12-06.
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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Yeah - I suspected that the DRASTIC goons might not appreciate getting the friendly doxxing. That's why I "archived" that particular paragraph above. It's OK if they publicly accuse people like Shi Zheng-Li of cover-up and mass murder and us of being running dogs on the take from CCP, but gosh they need their privacy.
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And here's Alina feeling "threatened" while engaging in conspiracy theories [not to mention publicly accusing people like Shi Zheng-Li of cover-up and mass murder and us of being running dogs on the take from CCP]. Zero sympathy for her BS. She has crossed many many lines. [shared file(s): image.png]
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So wait - the Medium post contained that email sent to me? Why would they even include that - it's so dumb....
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No - I pulled Dan/Harvard2Big House email to you from last March from here on Slack. Just pulling together the pieces. Dan Sirotkin is a big part of Drastic.
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Maybe this guy: https://www.mymcmedia.org/tag/daniel-sirotkin/
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Not sure how many ex-felons from Maryland go by Dan Sirotkin..
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Actually yeah same guy: https://www.homefacts.com/offender-detail/MD8455358/Daniel-Mandel-Sirotkin.html
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Seems nice. [shared file(s): image.png]
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Whoa - I missed the part about him being a sex offender. How novel.
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So here's his father: https://www.linkedin.com/in/karl-home-sirotkin-409b597b
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Which explains how this got written: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435492/
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Yup, all that I found too. Interesting couple - I'm sure dad must be proud.
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https://mygenomix.medium.com/the-origin-of-sars-cov-2-is-a-riddle-meet-the-twitter-detectives-who-aim-to-solve-it-5050216fd279
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It's back
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Perfect example of how a conspiratorial mind works. Fascinating. It's pretty clear they didn't bring the A-team in for this.
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Here's the NYT article about China's cover up - it's a very good one, but nothing new: https://www.nytimes.com/2020/12/06/world/asia/china-covid-origin-falsehoods.html?action=click&module=News&pgtype=Homepage
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I was just taking a closer look at the rooting of the pandemic. Our lineage A is definitely 2 nucleotides (1 amino acid) closer to RaTG13 than lineage B (Wuhan-Hu-1). But interestingly WA1 is one nucleotide closer still (out of a1150-odd, of course). It looks like the some of lineage A had a chance reversion (synonymous). But may be the cause of mis-rooting.
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In what sites? Lemme check the bam file to see how confident those RaTG13 calls are in those positions
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There are some low-coverage regions in that genome where you have ambiguous calls
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Just compared WA1 to Hu-1 and RaTG13. Only three differences between the two, all of them ancestral in WA1 - not Hu-1.
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What do you use as prototypical Lineage A?
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WH04
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Lemme include that too - and I should say, all those calls are fully supported in the RaTG13 assembly, so they're good
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It's that midpoint root.... Some early emergence funkiness.
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I have WH04 being identical to Hu-1, except the ends - do you have a different sequence?
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Hu-1 should have 2 differences from WH04 (EPI_ISL_406801): T:8781:C, C:28143:T
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Wuhan-Hu-1: T:8781:C|T:18059:C|C:28143:T WH04: T:18059:C WA1: 0:
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The version I have of Hu-1 (MN908947) is identical - weird... Lemme check again
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Yup, identical based on NCBI records (except the ends). Here's the Geneious alignment [shared file(s): 2020.12.06_alignment.geneious]
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WA1 has three differences to both WH04 and Hu-1 - all three ancestral.
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Lemme check these human sequences against the larger pango/bat alignment I have - since I have all the assemblies for those too.
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Not sure that is the same WH04 - there are some confusing names
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[and I'll see if I can get the raw data for WA1 so I can check the assembly for that one too - although it's been sequenced multiple times, so I assume it's correct]
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Lemme get WH04 from GISAID (I have been using MT291829 from NCBI as WH04)
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Comparing to all the pango/bat sequences here is interesting - in two out of the three positions (8782 (C/T) and(18060 C/T) where WA1 is ancestral compared to RaTG13, all the other pango/bat genomes have the same asRaTG13 - so definitely ancestral. HOWEVER, RmYN01 has the same derived residues in those positions as WA1. (Ican't check the third position - RmYN01 has bad sequencing around that position). Checking SARS...
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hCoV-19/Fujian/8/2020 I EPI_ISL_411060 -> seems to be identical to WA1 and sampled around the same time.
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SARS splits the differences.
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Compared to all the pango/bat genomes, those positions appear ancestral to me - Hu-1 and RmYN01 have derived residues in those positions.
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Here's an alignment - it's pretty messy and some duplicates... [shared file(s): 2020.12.06_pango-bat-sars2_alignment.geneious]
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Am I going mad - I just downloaded RmYN01 from GISAID and it is coming out as more divergent than RaTG13?
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Yes
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Doh. I was thinking of RmYN02
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I think it's fair to say that the lineage that led to WA1 > WH04 is probably older than the lineage that led to Hu-1.And yeah - RmYN02.. :wink: That one is ancestral in those positions too
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We have always used WH04 as the root -
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WA1 may be a more appropriate one - firmly placing the start of the pandemic in the United States :wink:
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Question is do we consider that WA1 (or more likely a Chinese genome such as hCoV-19/Fujian/8/2020) is basal to WH04?
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Out of curiosity, I also checked WH1-4 since they had those super funky ENA entries (still do.... SAMEA6507890 -SAMEA6507893) - WA1/WH04 basal to those as well. [shared file(s): 2020.12.06_early-genomes.geneious]
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I think considering WA1 basal to WH04 is appropriate based on that single difference
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(and I'd say ancestral here, since we have all the other genomes we can compare to)
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I think we know that WA1 travelled from Hubei (need to check) so that places the WA1 haplotype in Hubei
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Yup.
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Sampled in WA on 19-Jan
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I don't have my annotations right - which one is the non-synonymous change? Position 18060, which is the one thatdistinguishes WA1 from WH04 is the same in SARS as it is in WA1/RaTG13 (T)
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One other possibility - hCoV-19/Malaysia/MKAK-CL-2020-6430/2020|EPI_ISL_416886|2020-02-04 is one SNP from WA1. Pangolin connection?
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18060 is synon.
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How interesting... Yeah, that's a pango mutation
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The non-synon one is the one is 28189 in ORF8 S->L
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That was the first 'oh my god it is mutating' mutation
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Haha, historical significance for sure :wink:
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All of this is very interesting though - isn't this data most consistent with an early divergence (or two emergences)that we didn't capture at the time and that have no connection to the seafood market? In other words - entirely what one might expect?
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Oh - I have just seen what you just said - Malaysia is the same as the Pangolin at 6049 where it differes from WA1
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Yup
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ALL the pangolins have that one - none of the bats
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It is part of the pangolin which is more divergent than RmYN02
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But seems a weird coincidence given I pulled it out because of the Malaysian/Pangolin connection
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Synonymous though
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Haha, YES - I thought you had looked at the alignment!
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No - was just looking for ones related to WA1 that were from more plausible locations
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Given it is synonymous and the pangolin has loads of other mutations in that area it must be coincidence.
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Oh, but hang on - RmYN02 has 'C' in this position too - so pangos and RmYN02
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But spooky none the less
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Yeah, probably - but, yes, spooky.
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I think it's safe to say that we're definitely missing some early emergence stuff here
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... which is very interesting and worth a closer look. Would explain why we can't really root properly as well (Ihaven't checked recently, but back in the spring, BEAST insisted on a midpoint root when you took away the dates).
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Will do some experiments on BEAST dating with enforced WA1 outgrouping
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Okay, cool - I'll have a chat with Karthik too - we haven't been able to get good estimates of the root TMRCA recently, but that may very well be on us.
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I'm heading out for an hour, but once I'm back lemme just clean up these alignments a little and share - just so wehave them archived here. :beer:
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> On January 21, the Centers for Disease Control and Prevention (CDC) confirmed the first U.S. case in a 35-year-old man living in Snohomish County. He had returned from Wuhan, China after visiting his family there, tothe U.S., landing at Seattle-Tacoma International Airport on January 15, without any symptoms.
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And of course at that time Imperial College estimated Wuhan had 190-4000 cases by 12th Jan based on 3 exported cases.
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@Kristian Andersen They also used my quote out of context...I was just referring to some of those shonky studies, particularly the Indian-origin one.
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Yeah, clearly a lot more cases going around at that time than was appreciated - and obviously not (directly) linked tothe seafood market. We don't really see any evidence of other "WA1" lineages in Wuhan, do we? All those early ones were "Hu-1"?
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Probable scenario - ongoing undetected transmission in Wuhan building up, then a big super spreading event at the seafood market where it gets detected. Cases following are then connected to that event and most genomes are sequenced from the super spreading event, but not the emergence. Makes sense I think
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The emergence itself could have been anywhere, but transmission probably got going in Wuhan (but not at the seafood market - that's a SSE)
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"Anywhere [in China]"
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Total sense and I fully agree. I suspect the emergence event took place elsewhere and was imported into Wuhan.
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Can you just summarise where the root should fall? I didn't follow all that chain.
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WA1
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And by WA1 we mean a haplotype identical to WA1 that was in Wuhan before the 15th January
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Curious though that the Malaysian one is one SNP closer to RmYN02 than all the others. So possibly that one (but the January cases in Malaysia were Chinese nationals visiting)
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So I think most parsimonious would be `Malaysia/MKAK-CL-2020-6430|EPI_ISL_416886|2020-02-04` -> `WA1` -> `WH04` -> `Wuhan-Hu-1`
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(but all in Wuhan)
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Would it be worth trying to simulate a WA1 with a date in the beginning of December and run beast?
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shared file(s): image.png
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Given we see identical genomes spaced 6 weeks apart, I don't think we need to use imputed dates - just enforce WA1 to be an outgroup
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By the way - the C16T in WH04 is probably wrong, it is the very first nucleotide of that sequence. Should find abetter canonical lineage A
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Ah, yes - could be wrong. Let me see if I can pull the raw data
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I will find a better one - it isn't full length.
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Some cleaner alignments here with better naming, etc. [shared file(s): 2020.12.06_SARS-CoV-2_RaTG13.geneious, 2020.12.06_SARS2_SARS_SARS-like.geneious]