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0 pointshirenj4y ago0 comments

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 it good enough to get production of vaccines going on variants that are flagged, just in case?

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orintorynchus4y ago

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.

hirenjOP4y ago

Thanks for the info! That ability to retune sounds excellent. I wonder if you could spin this out to have an EWS for influenzas too (although hopefully it’ll never get as severe!)

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!

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