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Alphafold

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121–130 of 170 posts

Re: Alphafold

#121
post #69

I missed an important detail: """an academic team has developed its own protein-prediction tool inspired by AlphaFold 2, which is already gaining popularity with scientists. That system, called RoseTTaFold, performs nearly as well as AlphaFold 2, and is described in a paper in Science paper also published on 15 July""" One of the things I say about CASP has to be updated. It used to be "2 years after Baker wins CASP,…

I see an interesting geometric similarity between the two models, namely the attention mechanism that learns relationships between structure in embedded reference frames (i.e. 1D,2D embeddings in RoseTTaFold or "local" frames in Alphafold) and the true structure of the intrinsic space reference frames (3D coordinates in RoseTTaFold and "global" frames in Alphafold)

Re: Alphafold

#122
post #32

Honest question: since AlphaFold doesn't really _solve_ the protein folding problem (it's NP-complete after all), but only _approximates_ solutions very well, what are the real impacts of this? Isn't a good approximation of a protein enough to cause unexpected problems? How do we know that an approximate structure will perform the same as the correct solution?

AlphaFold is not about solving any kind of NP-complete problem. Proteins consist of chains of amino acids which spontaneously fold up to form a structure. Understanding how the amino acid chain determines the protein structure is highly challenging, and this is called the "protein folding problem". People use mathematical models to predict how proteins fold in nature. Many such mathematical models are stated in terms…

Thanks a lot for the detailed explanation :-)

Re: Alphafold

#123

Also announced today was RoseTTAFold from UW's Baker Lab, which claims nearly the same accuracy at much higher efficiencies. There's a public server and paper in Science. More info here and here: https://www.bakerlab.org/index.php/2021/07/15/accurate-prote... https://techcrunch.com/2021/07/15/researchers-match-deepmind...

That is the way, unlike AlphaFold, to publish everything in open source. Kudos to the research team!

Re: Alphafold

#124
post #16

Alphafold 2 is very very cool, but we need a little dose of reality. It's still a bit away from really solving protein folding as it was marketed. For example, multi-complex proteins are not well predicted yet and these are really important in many biological processes and drug design: https://occamstypewriter.org/scurry/2020/12/02/no-deepmind-h... A disturbing thing is that the architecture is much less novel than I…

>A disturbing thing is that the architecture is much less novel than I originally thought it would be, so this shows perhaps one of the major difficulties was having the resources to try different things on a massive set of multiple alignments. A similar concern has sparked some worries about "AI overhang" https://www.lesswrong.com/posts/75dnjiD8kv2khe9eQ/measuring-... Most of the compute in ML research seems to be g…

Self-driving is a cursed problem, but the thorniest obstacles relate to optics and politics and not technology. AI can already replace some human drivers some of the time; but it doesn’t matter because each news story about a Tesla killing a passenger or driving into a parked fire truck sets back public acceptance of self-driving cars by years.

Re: Alphafold

#125
post #83
post #35

Earlier quoted context omitted.

many of these resources are available, it's mostly that academic scientists don't have the time, money, or expertise to manage large datasets. However, the community has maintained high quality MSA database for decades and that's exactly the work that DM drafted off.

> academic scientists don't have the time, money, or expertise to manage large datasets I may be cynical about general expertise, as a support person, but large datasets have long been stock in trade of areas I'm more or less familiar with, whether "large" is TBs or PBs like CERN experiments. (When I were a lad, it was what you could push past the tape interface in a few days -- data big in cubic feet...)

The linked GH repo's readme says that it needs to download ~430GB and it takes ~2.5TB unzipped.

Re: Alphafold

#127
post #92
post #86

Earlier quoted context omitted.

Surely not all science. Just as well Dirac wasn't required to communicate that way the equation that fundamentally underlies the phenomenon discussed, and you couldn't put the unique facility my thesis work pioneered into git! I do highly approve of publishing software and data where possible, of course, since before Free Software needed to be coined, and it's much easier now.

If you're just publishing equations, you should have an associated notebook which executes the equations. I don't know what you mean you can't put your thesis work into git. Is it a physical thing? Too big for git?

Equations are math. They can be used analytically with pen and paper. No need to turn them into code.

Re: Alphafold

#128
post #81
post #77

Earlier quoted context omitted.

The key difference seems to be using the multiple alignments and assumption about evolutionary conservation? Useful for genes conserved, but less useful for de-novo proteins (like COVID and cancer) I guess?

Dunno yet. MSAs were always a key input to Rosetta (previous best method). How they were used was very different. Fundamentally, everything in this space (= non-physical methods) is about inferring structure from things that are closely related. And you can't solve the problem at all for non-trivial proteins using physics, so here we are.

> And you can't solve the problem at all for non-trivial proteins using physics, so here we are.

I'd appreciate if you could expand a bit on what you meant here, sounded interesting.

Re: Alphafold

#129
This isn't a criticism - I'm just curious to hear people's thoughts on this. When I look at this code, one of my initial reactions is that it does not seem to be very thoroughly tested. Sure, certain modules have been tested (e.g. `model.quat_affine`) but it's not clear how completely. Meanwhile, other modules, for example `model.folding`, have not been tested at all, despite containing large amounts of complex logic. That kind of code that works with arrays is very easy to get wrong and bugs are difficult to spot.

My experience working with code written by researchers is that it frequently contains a large number of bugs, which brings the whole project into question. I've also found that encouraging them to write tests greatly improves the situation. Additionally, when they get the hang of testing they often come to enjoy it, because it gives them a way to work on the code without running the entire pipeline (which is a very slow feedback loop). It also gives them confidence that a change hasn't lead to a subtle bug somewhere.

Again, I'm not criticising. I am aware that there are many ways to produce high quality software and Google/DeepMind have a good reputation for their standards around code review, testing etc. I am, however, interested to understand how the team that wrote this think about and ensure accuracy.

In general, I hope that testing and code review become a central part of the peer review process for this kind of work. Without it, I don't think we can trust results. We wouldn't accept mathematical proofs that contained errors, so why would we accept programs that are full of bugs?

edit: grammar

Re: Alphafold

#130

This isn't a criticism - I'm just curious to hear people's thoughts on this. When I look at this code, one of my initial reactions is that it does not seem to be very thoroughly tested. Sure, certain modules have been tested (e.g. `model.quat_affine`) but it's not clear how completely. Meanwhile, other modules, for example `model.folding`, have not been tested at all, despite containing large amounts of complex logic…

My understanding is that it has been manually tested. I.e. it has produced correct results to previously intractable problems. I'm not sure how much automated testing would add at that point.
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