The Deus Ex game series is known for fairly high-effort discoverable in-game writing, and I think this fictional e-mail from DXHR has renewed relevance after 15 years:
> We've been working with VersaLife’s new Chaos Model Genomatrix, which is trying to apply fractal mathematics to the study of genetic mutation. In essence, we've been trying to predict the future of human evolution using past mutations stored in the database of our mitochondria (which is passed uninterrupted from ancestral Eve through our mothers; it gives us an accurate and universal roadmap for our common past).
> The thing is… the sample you sent fits one of our evolutionary models of the future. We’re talking about someone who is ahead of the genetic curve by one step, maybe two. Do you know what this could mean for medicine alone? You have a living, breathing Nobel Prize on your hands!
And various dedicated AI models all made poor predictions of the results of that experiment, which casts doubts about the value of the AlphaGenome predictive map.
A virus is much simpler than a human, but even for that simple virus the effects of most of the mutations could not be predicted. A half of the mutations had harmful effects, and for a half of those it is unknown for now why they were harmful.
For a human the uncertainty about the effects of a mutation will be far greater than for one of the simplest viruses.
this is literally not possible. while I'm excited for these kinds of things, alphafold is already imperfect, and this basically side-steps actual structural predictions. it sounds good, but frankly biology is not there yet. in practice not even alpha fold can tell me if my gfp fusion will work...
The Deus Ex game series is known for fairly high-effort discoverable in-game writing, and I think this fictional e-mail from DXHR has renewed relevance after 15 years:
> We've been working with VersaLife’s new Chaos Model Genomatrix, which is trying to apply fractal mathematics to the study of genetic mutation. In essence, we've been trying to predict the future of human evolution using past mutations stored in the database of our mitochondria (which is passed uninterrupted from ancestral Eve through our mothers; it gives us an accurate and universal roadmap for our common past).
> The thing is… the sample you sent fits one of our evolutionary models of the future. We’re talking about someone who is ahead of the genetic curve by one step, maybe two. Do you know what this could mean for medicine alone? You have a living, breathing Nobel Prize on your hands!
(Megan Reed's computer, in the prologue.)
Meanwhile someone went and did the experiment on the equivalent problem in a virus: https://www.science.org/content/blog-post/mutate-em-all-and-...
And various dedicated AI models all made poor predictions of the results of that experiment, which casts doubts about the value of the AlphaGenome predictive map.
A virus is much simpler than a human, but even for that simple virus the effects of most of the mutations could not be predicted. A half of the mutations had harmful effects, and for a half of those it is unknown for now why they were harmful.
For a human the uncertainty about the effects of a mutation will be far greater than for one of the simplest viruses.
If you like that abstract geometric headline image, you might also like the source artist their model “learned” it from: https://leegriggs.com/xgen-rendered-with-arnold-for-maya
the catch with a genome-wide map is the benchmark labels came from conservation, so you can't tell prediction from re-reading the prior.
> benchmark labels came from conservation
And from human disease...?
this is literally not possible. while I'm excited for these kinds of things, alphafold is already imperfect, and this basically side-steps actual structural predictions. it sounds good, but frankly biology is not there yet. in practice not even alpha fold can tell me if my gfp fusion will work...
gfp --- green fluorescent protein
glow in the dark jelly fish bits that biologist stick in other critters to see if, when and where it shows up (under a blacklight).
Some more discussion: https://news.ycombinator.com/item?id=49611251