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BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

investors.biontech.de

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Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#31

Post by axg11 »

orintorynchus wrote: post #23
axg11 wrote: post #3

Impressive if true, although I am very sceptical of the results. The real test is to put their neck on the line and predict/warn of the next significant variant. If the authors are not willing to do this, I doubt that the algorithm is useful. 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…

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

Thanks for adding this information. I was unfair to judge so harshly and be so sceptical.

So the $1T question is ... what (if anything) is this model currently predicting about the next variant?

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#32

Post by carbocation »

spuz wrote: post #18

> More than 10,000 novel variant sequences are currently discovered every week and human experts simply cannot cope with complex data at this scale 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 g…

Public messaging often includes the more extensive PANGO lineage (e.g., B.1.1.529 for Omicron). I think there is a limit to what can be conveyed in each news story.

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#33

Post by oger »

orintorynchus wrote: post #23
axg11 wrote: post #3

Impressive if true, although I am very sceptical of the results. The real test is to put their neck on the line and predict/warn of the next significant variant. If the authors are not willing to do this, I doubt that the algorithm is useful. 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…

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

A massive thanks for the work you put in - I am sure it will pay off manifold. Assuming your models are robust over time this will clearly help the development pipeline of BioNTech / Pfizer to come up with adjusted vaccines should the need arise (i.e. an especially nasty mutant showing up). Shortening the detection from weeks (months?) to days is an order of magnitude gain in lead time. From a commercial point of view this agility will give BioNTech / Pfizer a lead over its competitors (assuming this is not public / shared information?)

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#34

Post by orintorynchus »

im3w1l wrote: post #30
spuz wrote: post #18

> More than 10,000 novel variant sequences are currently discovered every week and human experts simply cannot cope with complex data at this scale 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 g…

Well to be classified as a variant it would have to be phenotypically different right? And also viable enough to infect a number of people.

Well, there is a lot of overlapping nomenclature. Here by variant we understand any sample, which is not identical sequence-wise to sequences seen before. Most of the observed mutations are innocuous and do not lead to a potential new lineage (what better fits the definition of variant above). However, it is difficult to tell by eye - or even with the standard computational tools - if new mutation is (a) deleterious (harms the virus' capacity to spread), (b) neutral, or (c) fitness enhancing.

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#35

Post by orintorynchus »

oger wrote: post #33
orintorynchus wrote: post #23

Earlier quoted context omitted.

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

A massive thanks for the work you put in - I am sure it will pay off manifold. Assuming your models are robust over time this will clearly help the development pipeline of BioNTech / Pfizer to come up with adjusted vaccines should the need arise (i.e. an especially nasty mutant showing up). Shortening the detection from weeks (months?) to days is an order of magnitude gain in lead time. From a commercial point of vie…

What we hope for is rather informing the public policy. Now, any time a scary looking variant is sequenced, there is some public commotion, uncertainty about the future repercussions. We want to be able to gauge the appropriate level of concern in these situations. It is not an all-knowing oracle, but rather a way to distill the insights from prior observations and simulations, the same way a human expert would do. This being said, we believe that the insights provided by EWS can be of use in designing new vaccines, as well as deploying the existing ones most effectively.

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#37

Post by orintorynchus »

hirenj wrote: post #28
orintorynchus wrote: post #23

Earlier quoted context omitted.

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

Dear Marcin - congratulations on the manuscript! 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…

The system is constantly learning, so it "retunes" itself. We can infer epitopes from structure, but we found that data derived from known complexes is sufficient for our purpose.

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.

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#38

Post by [deleted] »

twofornone wrote: post #22

>More than 10,000 novel variant sequences are currently discovered every week and human experts simply cannot cope with complex data at this scale 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…

[deleted]

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#39

Post by orintorynchus »

whycombagator wrote: post #25
orintorynchus wrote: post #23

Earlier quoted context omitted.

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

Thank you for chiming in. It’s great that you detected them. I’m curious how many false positives you had during that same time? Did you detect many others that just didn’t pan out to be of significance?

This is something that amazes me. Any time a true High Risk Variant appears, it is clear as day in the system. This was the case with Lambda, Mu (which we predicted to have a limited propensity to proliferate), and now with Omicron. However, there are lineages, which are prospectively dangerous, that we detect. As the classification is relative, there is no fixed threshold beyond which we would call for alert. In the evaluation, we have been looking at 20 sequences per week, as this was roughly the testing capacity of our partners. Going for ONE sequence a week makes us detect some variants a bit later, but still. The sequences and lineages we predicted to be of interest were predominantly spreading afterwards. Some were just a blip on the radar, though. We aimed at sensitivity and not missing ominous signs, rather than specificity. NB: Each week there are thousands (now 12k+) new sequence variants. Out of them we consider 20. And detect most of the variants as early on as on the first day.

Re: BioNTech-InstaDeep Early Warning System to Detect High-Risk SARS-CoV-2 Variants

#40

Post by orintorynchus »

zxexz wrote: post #27
orintorynchus wrote: post #23

Earlier quoted context omitted.

I am the second author of the paper. We have been putting our head on the line for the last half a year. We detected Lambda, Mu (with a caveat, that we did not consider it competitive) and Omicron - all blindly. 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, p…

Wow, amazing to see you here. I have somewhat of a bioinformatics background, and this is the sort of work that I always found very interesting - do you think your team will produce some sort of high level architectural and process breakdown at some point?

I am sure we will, in due time. If you have any particular hopes or wishes, we will try to accommodate as much as we can.
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