BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants(investors.biontech.de) |
BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants(investors.biontech.de) |
This is interesting. I think the Greek alphabet naming system would lead some people to believe the virus only mutates once every few months. Of course, the reality is that every infected individual will produce hundreds of mutations within their body. I think there's a gap in the public messaging here which if addressed could help people understand what the future direction of the pandemic might be.
https://www.wnycstudios.org/podcasts/radiolab/articles/dispa...
We as a society tacitly "outsource" the task of becoming an expert to a bunch of mostly smart and well-meaning folks, in all sorts of areas, because we cannot all know "everything" - and for some reason on vaccines and epidemiology great swathes of the population, including senior leaders politically, now choose to ignore their clear guidance on how best to act.
As a side note, the first author on this paper is the CEO of InstaDeep. I see it as a red flag that the CEO of a 150+ person company would put themselves as first author on this paper. Perhaps I'm unfairly judging and the CEO really was the lead contributor to the study.
> When using a weekly watch-list with a size of 20 variants (less than 0.5% of the weekly average of new variant sequences), EWS flagged 12 WHO designated variants out of 13 (Fig. 4.A), with an average of 58 days of lead time (i.e two months) before these were designated as such by the WHO (Table S.4).
> Our system however does not accurately pinpoint the emergence of the B.1.617.2 Delta family of variants. Delta is known to be neutralised by vaccines24 and its global prevalence can be attributed to other fitness-enhancing factors [than immune escape]. These factors, such as P681R mutation, which abrogates O-glycosylation, thus further enabling furin cleavage, are outside of the scope of our approach.
> Specifically, the EWS identified Omicron as the highest immune escaping variant over more than 70,000 variants discovered between early October and late November 2021.
I suspected something like this, given the frequency of viral mutation. Officials announce a dominant global strain but what proportion of positive cases are actually sequenced and evaluated for confirmation? How many undiscovered strains are actually in circulation at any given time, in geographically isolated areas? Could that explain variability in severity and/or long covid?
Claims that spike affinity for ACE2 (or indeed changes to the spike protein at all) haven’t been conclusively proven to increase fitness as far as I know. It’s possible that this tool is simply overfit to the known variants and wouldn’t detect a new one.
I’d be interested to hear what real virologists think of this.
Like what is the harm in doing the data collection and publishing about how it is going?
I'm fully vaccinated, but more data points to come up with media fear mongering is the last thing anyone in the developed world needs right now.
But the idea above directly follows from the work in the paper.
https://www.instadeep.com/2022/01/biontech-and-instadeep-dev...
We have been verifying all our predictions experimentally, post factum. And the method is purely data driven - with no fitting to the experiments or observations.
The first author came up with the approach, participated in analysis and got his hands dirty as everyone else. While he is a CEO of a 160+ person company, this has been a labor of love for all of us, done to a large extent in the evenings, during weekends and holidays. It is indeed an unusual situation. But this was not a regular project and InstaDeep is not a regular company either.
Do you think the immune escape parameters would need to be retuned in a post Omicron world? Do you need the actual epitopes recognised by antibodies, or can you guess this from structure.
Do you capture any aspects with respect to changes in spike glycosylation in your models?
Finally, as with another reply, do you have a guess about the specificity of this system? Is it good enough to get production of vaccines going on variants that are flagged, just in case?
So the $1T question is ... what (if anything) is this model currently predicting about the next variant?
It’s like how people said Y2K was just a conspiracy theory because most systems kept running — without realizing the early warnings and preparations is the reason Y2K wasn’t a civilizational disruption.
Authors on scientific papers are ordered by name, so whoever's name is first is pure coincidence.
In this case I notice that they first sorted all the instadeep people to the front, and biontech people to the end... not sure what I'm supposed to take away from the ordering, but it's not random.
> Molnupiravir is indicated for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19.[1][5]
So after the risk of creating mutations in the Covid virus has been assessed and weighed against the chances of patients just outright dying due to not having this medicine available, the board full of medical professionals trained in this matter voted 13 to 10 that they thought the risk was acceptable.
That's very likely not even possible[1]; and, it not being realistic, would be a waste of time, effort, and money. There are lots of corona viruses that we have never stopped, and we live with via herd immunity, hygiene, and therapeutics[2].
[1] https://www.acsh.org/news/2020/11/05/covid-why-we-will-never...
[2] https://www.cdc.gov/coronavirus/general-information.html
> "The emergency use authorization was only narrowly approved (13-10) because of questions regarding efficacy and concerns that molnupiravir's mutagenic effects could create new variants that evade immunity and prolong the COVID-19 pandemic."
The quote above has its own citations in the Wikipedia page posted by GP.
It's unclear why that is relevant in this thread though.
Because creating mutations and prolonged pandemics are more profitable.
OTOH, Molnupiravir works by: (quoting from Wikipedia again)
> [it] exerts its antiviral action through introduction of copying errors during viral RNA replication.
So it deliberately stops virus reproduction by introducing errors in RNA copying. The vast majority of time this just makes the virus nonfunctional, but it is technically not impossible that it creates a viable mutated strain. This mutated strain may or may not be worse than the original virus. It is not unsimilar to how `cat /dev/urandom | bash` just MIGHT start off with `rm -rf /` and delete everything, but usually it will just create a crash because the random bytes don't parse into a valid bash command.
Current version of EWS does not explicitly account for glycosylation. It is implicitly handled by the ML models, though.
For specificity, it is difficult to estimate. We know that for each of the named Variants of Concern, the signal from EWS was unmissable. Considering, that any new vaccine would need to go through a stringent approval process, I don't think that EWS should be a major determining factor in the process. However, it can certainly help resolve the doubts.
I guess for the glycosylation when you say it’s implicitly handled, there’s a N-linked sequon pattern somewhere in the language model, which I guess covers a good deal of info :)
Jury still out on effects of O-linked glyco on spike, but give me a shout if you’re interested in it!
Anyway, cool work, and all the best in where you’re taking the work next!