Earlier quoted context omitted.
Here's another blue check immunologist on twitter with a substantially different take: https://twitter.com/K_G_Andersen/status/1583252866394771456
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
Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
141–150 of 250 posts
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#142Earlier quoted context omitted.
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.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#143Earlier quoted context omitted.
They did share it with scientists. Here’s Francois Balloux saying he replicated the results, tried to find holes, couldn’t https://mobile.twitter.com/BallouxFrancois/status/1583165259...
Here's another blue check immunologist on twitter with a substantially different take: https://twitter.com/K_G_Andersen/status/1583252866394771456
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).
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#144The lab leak hypothesis is the “jet fuel can’t melt steel beams” of our day.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#145There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…
>Thirdly, this paper emphasizes the strong impact of the COVID pandemic and asserts that understanding the origins of the virus would necessarily aid in preventing future pandemics. This does not clearly follow. Especially if the virus had natural selection origins there is no clear and obvious way of systematically reducing risk. Simply living or traveling where host populations like bats live could be enough to gen…
> first purposeful extinction
Smallpox? And extinction of Guinea worm is in process.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#146"To avoid losing power with multiple comparisons, we focus our analysis on the BsaI/BsmBI sites in SARS-CoV-2 and compare the BsaI/BsmBI map in SARS-CoV-2 to all other restriction maps of all other CoVs used in our analysis." It's important to know whether or not the authors picked BsaI & BmBI blind, before looking at the genome. If they picked BsaI & BmBI with knowledge of the SARS-CoV-2 genome, that doesn't dodge t…
> It's important to know whether or not the authors picked BsaI & BmBI blind, before looking at the genome. You could never convince me that these restriction enzymes were picked blindly, no bioinformatician I have ever met does science this way. There is a preliminary period of exploratory data analysis which is done before any hypothesis is put forward, and data dredging and leakage are rampant in the literature. T…
> To your point however, could someone comment on the suitability of BsaI/BsmBI for the in vitro assembly of synthetic coronaviruses?
These are very commmon enzymes. Perhaps the most common today.
The GP comment is sort of misleading...you wouldn't just pick enzymes at random to do this analysis. You'd pick the enzymes in common use. These count.
> Is it all just about finding sites in the genome at the right locations which can be turned into restriction sites without disrupting any existing functional genetic elements? or is there more to it than that.
You can add or remove sites using different techniques, such as PCR mutagenesis.
> If a research team were to come along and decide they wanted to engineer their own coronavirus, how likely would it be that they would choose these restriction enzymes?
Highly likely.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#147.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#148There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…
Their claims around Type IIS assembly are also suspect. eg in Golden Gate assembly, you choose Type IIS that reach over and cut, so the restriction site is absent from the final assembled product. "Additionally, because the final product does not have a Type IIS restriction enzyme recognition site, the correctly-ligated product cannot be cut again by the restriction enzyme, meaning the reaction is essentially irrever…
Their description of the assembly strategy as "Golden Gate" seems like incorrect terminology. The WIV has at least published papers using BsaI and BsmBI, though.
https://twitter.com/jbkinney/status/1583267221047869441
https://twitter.com/jbkinney/status/1583248052969562112
https://journals.plos.org/plospathogens/article?id=10.1371/j...
EDIT: Kinney also asserts here that they left the sites in a final assembled genome (i.e., the genome of a replication-competent virus). I'm still trying to figure out if that's true, though.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#149There's a line in this paper which has been cited a few times in this thread which really stands out to me: > 100,000 random in silico mutants were generated for both RaTG13 and BANAl-20-52...Only 1.2% of RaTG13 mutants resulted in a BsaI/BsmBI restriction map with a larger z-score than SARS-CoV-2. BANAL52 is the closer relative to SARS-CoV-2 by over 200 nucleotides, yet only 0.1% of mutants yielded z-scores as great…
But the thing they're evaluating does not have an evolutionary benefit, so the fact that many possible mutated viruses exist does not mean it's any more likely that this specific pattern would be observed in a specific pandemic virus.
Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?
#150There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…
Their claims around Type IIS assembly are also suspect. eg in Golden Gate assembly, you choose Type IIS that reach over and cut, so the restriction site is absent from the final assembled product. "Additionally, because the final product does not have a Type IIS restriction enzyme recognition site, the correctly-ligated product cannot be cut again by the restriction enzyme, meaning the reaction is essentially irrever…
Just because there are more modern techniques doesn't mean there haven't been older ones used, or techniques used incorrectly.