--- type: Conversation title: Private channel session 1607 description: "slack conversation, 36 messages, 2021-09-21." tags: - conversation - slack medium: slack message_count: 36 started_at: "2021-09-21T08:01:59" ended_at: "2021-09-21T09:41:18" duration_seconds: 5959 sources: - { id: slack_pm, resource: /sources/slack-pm.md, title: Slack / Private Message Drop, author: "process:senate-hsgac-release" } generated: { by: randpaul-corpus-pipeline/1.0, at: "2026-08-01T12:42:27Z" } status: stable --- A slack conversation of 36 messages spanning 1h 39m. # Metadata - **Started:** 2021-09-21T08:01:59 - **Ended:** 2021-09-21T09:41:18 - **Duration:** 1h 39m - **Participants:** 3 - **Source:** [slack_pm](/sources/slack-pm.md) - **Pages:** 999-1002 # Participants * [Andrew Rambaut](/people/andrew-rambaut.md) * [Edward C. Holmes](/people/edward-c-holmes.md) * [Kristian G. Andersen](/people/kristian-g-andersen.md) * [Robert F. Garry](/people/robert-f-garry.md) # Transcript **[2021-09-21T08:01:59] Kristian G. Andersen:** IMO we really _do_ need to take a close look at what's described in this grant and look back at our (now expanded)alignments to see if anything pops up. E.g., Bob mentioned that there are differences in Laos bat vs SC2 when itcomes to N-linked glycans, which isn't particularly reassuring - that's the kind of work described on page 11. **[2021-09-21T08:05:12] Andrew Rambaut:** I agree - need to stay on top of this. **[2021-09-21T08:05:42] Kristian G. Andersen:** Yes - this can't (shouldn't) be dismissed out of hand. **[2021-09-21T08:06:07] Andrew Rambaut:** If there is anything suspicious - better that we say it and then address it. If there isn't then we can let it blow over. **[2021-09-21T08:06:40] Kristian G. Andersen:** Exactly. I suspect it'll be the latter. **[2021-09-21T08:08:52] Andrew Rambaut:** Me too. But it really isn't beyond plausibility that someone went ahead and tried some of this stuff. We just need tore-convince ourselves it is coincidence. **[2021-09-21T08:10:14] Kristian G. Andersen:** Correct - that's the problem. There's a big difference between "the lab was working on bat CoVs" to "the lab wasmodifying bat CoVs using features we see being unique to SC2". **[2021-09-21T08:10:33] Andrew Rambaut:** Key question is - would anyone chose to put the FCS we see in SC2 in and put it out of frame. **[2021-09-21T08:11:21] Kristian G. Andersen:** Would be a very strange way to do it, but not impossible - depending on their cloning strategy. **[2021-09-21T08:12:04] Andrew Rambaut:** If you wanted to insert an FCS you would pick the AAs you wanted, pick the codons you wanted and then insert it. **[2021-09-21T08:12:46] Andrew Rambaut:** The alternative is that it was inserted in frame and then mutated to make it look out of frame **[2021-09-21T08:14:19] Kristian G. Andersen:** Again, it depends on cloning strategy - if the use restriction enzymes and there would be an easy way to insert anFCS with PCR utilizing REs already present in the sequence, then it could be a way to do it. Not the optimal way, for sure, but sometimes ease trumps perfection. **[2021-09-21T08:16:32] Andrew Rambaut:** Would you pick CGG for example? Would you consider what codon to use for an R or just pick one arbitrarily. **[2021-09-21T08:21:23] Kristian G. Andersen:** CGG would be an unusual choice IMO - not a 'optimized' R and sorta middle-of-the-pack as it comes to usage in human genomes. Very rare, of course, in viruses because it's a CpG. **[2021-09-21T08:24:03] Andrew Rambaut:** And you have 6 codons to chose from. **[2021-09-21T08:25:24] Kristian G. Andersen:** Correct. Key here too is that if you were to 'optimize' the FCS sequence (as is commonly done for these types ofexperiments) you would _not_ end up with the FCS sequence we see, including the CGG codons. But again, itdoesn't really tell us much. **[2021-09-21T08:26:15] Kristian G. Andersen:** What I think we have to look _very_ closely at are all the specific sites they talk about in the grant and then compare across our alignments - is SC2 unique in those positions compared to, say, the BANAL viruses? Does it flip back toSARS1 at some of these positions, etc. **[2021-09-21T08:26:48] Andrew Rambaut:** Yup. **[2021-09-21T08:27:39] Kristian G. Andersen:** I'll get some of this started later today - it's important to get the insights irrespective of what it's going to end upshowing. **[2021-09-21T08:28:55] Andrew Rambaut:** Would there be any reason to pick the SARS2 backbone for doing these? Assuming they had the genome sequence way back at the start? **[2021-09-21T08:30:30] Kristian G. Andersen:** Well, in the grant they specifically talk about *new* viruses - so a SC2 precursor could have been one of those "low risk" viruses they talk about and then they started fiddling with it. **[2021-09-21T08:34:27] Andrew Rambaut:** They would have selected it from candidates by genome sequencing it. I guess they would have seen an ACE-2 binding RBD and thought that is the one to try an FCS in? **[2021-09-21T08:37:08] Andrew Rambaut:** Or they just were selecting viruses by seeing if they could get any to culture and then worry about genome sequencing? **[2021-09-21T08:48:58] Kristian G. Andersen:** The former - which is the approach they describe in the grant. **[2021-09-21T08:49:44] Kristian G. Andersen:** Culture is very challenging so I don't think that approach makes sense. **[2021-09-21T09:00:15] Kristian G. Andersen:** Here's what I suggest we do: • Make (spike) alignments with SC1, SARSr-CoVs, RaTG13(+close friends), Pangos, BANAL, SHC014, rs4237, SC2 • Mark 'key' sites based on what's in the grant - @Robert Garry, can you please help highlight the N-linked glycans based on Wuhan Hu-1 coordinates• Check to see if there's anything odd between SC2, basal viruses, and SC1• Look at e.g., codon usage at those sites if anything stands out• Cross-check with how those sites have evolved during the pandemic **[2021-09-21T09:01:22] Andrew Rambaut:** And stay off email **[2021-09-21T09:02:00] Andrew Rambaut:** Or carefully curate some emails for the FOI records **[2021-09-21T09:07:39] Robert F. Garry:** OK I'm on my bit... **[2021-09-21T09:07:43] Kristian G. Andersen:** Exactly - let's dig around a little and then start an email chain. I'm in Zoom calls most of the day, but I'll dive in in the afternoon. **[2021-09-21T09:09:52] Kristian G. Andersen:** Actually, let me get started - I just cleared my calendar for the next hour. **[2021-09-21T09:34:20] Robert F. Garry:** Is this a good set for the SC1 related viruses - or others (some more civet ones)? [shared file(s): image.png] **[2021-09-21T09:35:11] Kristian G. Andersen:** I'm getting (and annotating) the genomes now **[2021-09-21T09:37:43] Andrew Rambaut:** Ooh.. Can't wait. **[2021-09-21T09:39:31] Andrew Rambaut:** Probably worth having the full genomes aligned even if we only focus on the close relatives in the spike **[2021-09-21T09:41:18] Kristian G. Andersen:** Yup - I'm getting all the full length genomes first and then we can cut alignments out from there. Getting them annotated too - future Kristian will thank present Kristian.