The authors of this paper are confused about the technology they're using... it's not a good sign about their conclusions..

https://twitter.com/matias_kaplan/status/1583235087067336704

https://twitter.com/NoahOlsman/status/1583275862442807299

Oh dear... Yeah, the author affiliations on the title paper made me wonder if they knew what they were doing at all.

Their terminology would indeed seem wrong, but the WIV has apparently used a similar assembly strategy (leaving the sites in the final assembly) before:

https://twitter.com/jbkinney/status/1583267221047869441

I'd worry about their false discovery rate, for the same reason I worry about the large number of parameters in Pekar's epi model. It's still an interesting result, though.

As far as I've been able to read, those sites aren't in the final assembly in Shi's papers - just in the primers. And even more worrying than the false discovery rate are all of the missing genomes they should be comparing. I fear they've left them off because they punch big ole holes in the theory... e.g.

https://twitter.com/zhihuachen/status/1583258714340892672

> As far as I've been able to read, those sites aren't in the final assembly in Shi's papers - just in the primers.

Where did you read that? Kinney explicitly asserts the opposite, but I can't figure out what he's referring to. Someone else linked to Figure S9 from their 2017 PLOS Pathogens paper, which indeed seems not to contain the site in the final assembly. I've edited my other comment here to reflect that.

Nope - the restriction sites aren't in the final assembly in that paper. These authors just don't understand the tools remotely well enough to have written their paper. It will never be published.

https://twitter.com/alchemytoday/status/1583361758903013376

Yeah, I think Kinney is wrong here. Someone else found a survey paper noting the theoretical possibility of using BsaI and BsmBI in a way that leaves the sites in the final genome, but I haven't seen anyone who actually did that. So I'm leaning to a false discovery here.

Another good twitter thread on it this morning:

https://twitter.com/acritschristoph/status/15834864034169692...

And Francois Balloux seems to have deleted his twitter account this morning.

As far as I can tell, WIV (and other) researchers have left other restriction sites in final genomes, but not BsaI and BsmBI sites. That makes sense given the typical use of those two enzymes. So I'm inclined to agree there's nothing obviously special about that combination of restriction sites and spacings, which increases my concern that this is just a false discovery.

Jesse Bloom said he'd try reproducing with a wider range of natural viruses and potential synthetic assembly strategies. Unless and until that still gets an interesting p value, I'd agree this is oversold.

or not: https://twitter.com/VBruttel/status/1583233001319956480

It feels telling that when I click that link, the associated tweets are the kookiest of conspiracy theories about Pfizer execs, vaccine mandates and people screeching about things they clearly don't understand. I suspect in a few days, with Bloom and others reviewing the preprint they're going to be forced to pull it down and "rework" it.

It's incredible that the only sensible comments on this thread are this far down. The HN audience really has a massive Dunning-Kruger problem when it comes to science topics (especially true for COVID conspiracy theories).

As a pharmacologist reading the HN crowd arguing about hydroxychloroquine a year or so ago really highlighted 90% of this site regarding topics other than development or start-ups is at the same level as youtube comments, but with more arrogance.

Eh... That's why it's important to speak up and teach where you can. You never know who might learn something, and you may find yourself learning something in return.

Nobody gains anything in silence however.

I had the same experience a couple of years back when people started discussing AI. I try to keep this in mind but somehow I keep forgetting. It’s genuinely difficult to filter good from bad takes without expert level understanding of a topic unfortunately.

Please don't link to Twitter, we are trying to have a high level of conversation here, we don't need any "takes" from the kind of people that still use Twitter.