That is outright scary. Science is being slurped up here.
The gist was, can existing variation provide enough context to infer impact of variation? The answer seemed to be no.
Kind of like how frontier LLMs need to ingest larger and large amounts of text to advance. We are going to need to leverage comparative data from other species, and likely tremendous amounts of laboratory mutagenesis experiments to actually make headway on variant prediction. Nature, as it stands, just doesn't have enough human variation.
Is this saying that if we were to sequence every human being on the planet, we'd still be unable to explain some phenotype differences caused by variation simply becase there aren't enough humans/enough variation? Interesting, as that's the first time I've heard that claim, and it would suggest that we spend our time working on mechanistic models of variant to phenotype.
https://www.science.org/content/blog-post/mutate-em-all-and-...
which comments the results of this study:
https://www.biorxiv.org/content/10.64898/2026.07.25.740675v1
That study has done in reality what the AlphaGenome Atlas does in fiction, but instead for a human they have done it for one of the simplest viruses.
So they have fuzzed the virus by mutating one by one each position of its DNA.
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.
The real value of AlphaGenome is not the effect of SNPs on protein coding regions (there are other tools for that, like AlphaFold), but rather identifying regulatory elements, such as promoters or alternative splicing patterns or microRNAs, within the ~98% of the genome that hasn't been well characterised yet.
That 98% is vastly underexplored, so a tool like this could help researchers interested in expression profiles or alternative splicing patterns of a protein, identify the source. Obviously not every "important" SNP will be consequential, but it helps narrow the search for that needle in a haystack.
For a machine intelligence to turn DNA sequences into organisim phenotype prediction requires modelling all that in latent space.
I imagine that is going to take a monumental amount of example data
I would not group AlphaGenome into the pile of failed predictions of other models. AlphaGenome deserves to get evaluated based off its own merits.
Imagine cellular activity as an industry zone, its not just what you can or can not make, its also 'for what concentrations of chemical species, what transcription rates should be used' so apart from the discrete Mendelian aspects (like what eye color or what have you) there is also a concensus sequence and deviations from consensus. They mention the dataset captures non-coding DNA, which should imply promoter sequences. Will it be possible to query the atlas for joint probabilities of promoter and putative target protein occurence in human genomes?
Personalized medicine could never credibly take off as long as promoter sequences were excised before sequencing!
Also Mendelian has little to do with promotor sequences or differential transcription in deviations.
23andMe used a custom Illumina Infinium microarray designed around segments of particular interest.
It's unlikely that they would luck into testing some unknown SNP which turned out to be relevant for disease.
Those SNP's i believe are testd from primers
so what 23andMe does is specifically on the back of previous research and afaik their data isnt technically clinically significant as most findings need confirmation or more tests.
As someone who regularly investigates whole genomes I would love to use this as a tool on novel mutations. These folks are the edge cases no one else could figure out that I get a crack at. Beyond the DNA we have the symptoms and lab work and I can usually narrow it down to a handful of guesses, but it sure would be nice to use this to help rank where to invest efforts.
For now i'll treat it as just another fun Google project that might come out of beta one day (or not).
This is exactly what the various DeepMind products have been for, and this simply aggregates them. Why are you unable to use this for candidate discovery when that's exactly what it's for? Is this because you do gene discovery in a commercial setting?
I'm comfortable programming but others who also do mol bio may be less so or may not recognize when Claude is going off the rails.
Very excited to see that happen here.
I don't want to drag the discourse away from this achievement, but I hate how this is announced with blatant corporate advertising (our internal model, here are the benchmarks, gpt astra TM yours now for the low low price of £200pcm). I just didn't think Navier-Stokes falling would be sponsored by McDonald's.
Still. I am crying right now. Navier-Stokes is solved.
https://deepmind.google/blog/alphagenome-atlas-a-predictive-...
They are only announcing a cache. The origin for the cache is not discussed.
In particular, the question of whether to trust the predictions is not addressed. For that, I think the citation is from January:
This is for a database, no? While Borzoi is a model?
> Here, we introduce Borzoi, a model that learns to predict cell-type-specific and tissue-specific RNA-seq coverage from DNA sequence.
Check out VIPdb for the broad category of methods/databases
https://genomeinterpretation.org/vipdb.html
These are predictors for "pathogenicity". Which is the vague concept of "does it cause genetic disease in humans" where "disease" itself is defined as the broad set of things that "brings patients into the doctor to figure out what's wrong."
The "regulatory impact" part of this is what differs from other predictors, in that it predicts the internal states as measured by several different assays, such as transcription regulating proteins are bound where in the genome, etc. Those predictions may or may not be usefel to people trying to reason about things going on in the cell, but my guess is that it's not going to get much use my molecular biologists, because the way the paper was described is pretty bad, and there are no experimental results I saw towards validating that.
But then, I'm not super interested in this paper. It's my field, but if there's something interesting I'm sure I'll hear about it from colleagues. Google is a fantastic advertising company that sometimes also does a bit of science, but this PR push is just an advertisement. A standard work-a-day paper gets covered as if it were ground breaking, and it will get enough eyes that I feel like I can safely ignore it until somebody in the field points out something interesting.
Can you elaborate on this? I'm confused why Google would build something that provides zero improvements over SOTA, Borzoi... as you mention. I'm not familiar with this field, just curious.
Imagine if the Apple EV had actually happened, you think the EV enthusiasts would roll their eyes like you are?
Please stop accusing or hinting at others being a language model or bot. Not only is it a dumb waste of time, it's wrong in this instance and you are not only going to continue to be wrong but you have no way to prove or demonstrate that any single post comes from a bot nor the ability to do anything about it if you did in fact believe some comment to be attributed to a bot.
The set of who can actually use this is pretty much null as it is. You cannot use it in a publication, nor for any clinical purposes.
There is a "permanent delete my data" option, but there's no independent audit that permanent delete actually deletes anything. If you're in EU/California they kinda have to take delete seriously due to GDPR and CCPA, so I think you're safer here.
I've been thinking about this a lot, and I'm not sure how "protectable" your DNA actually is because of how easy it is to get if somebody wants to. Obviously having your DNA in US government is bad, but they likely have it already.
As I'm an EU citizen I will get the data and use the delete option with fingers crossed that US government doesn't want to destroy me for whatever reason. Seems like they have their hands full with other kinds of destruction anyway lol
Alphafold or Earthquake alerts for example spring to mind.
You could argue about comprehensive "free" services (search, Gmail, YouTube, docs, etc) and "free" browsers and "free" operating systems (yeah plural) being net positives in the world but I know that many people view these as negatives as they (rightly or wrongly) view them as vehicles to sell ads or collect data, but I bet you 100 bucks the typical person on the street using their android phone to search Google, watch YouTube, check their Gmail, write a doc, view photos etc doesn't give a shit about that and values these things - google has ended up as a monopoly as these things are actually pretty useful to people and thus valued, even if we in the tech world disagree with the adtech and data aspects. This monopoly was not a fait acompli or pure market abuse - Nokia, MS, flikr, Hotmail, yahoo etc were all incumbent and market dominant but are now irrelevant because the Google products were viewed as better by end users.
What's your alternative? Executive fiat? Mob rule?
Deepmind is objectively good. These endeavors would always cost money. Better private capital than state, no one has to give Google anything. The state is not so generous.
Only if the goal is profit. All else be damned.
> What's your alternative? Executive fiat? Mob rule?
It is always bewildering to me that people see the world being raped by corporations and their negative externality, and they think that this is the pinnacle that humanity can achieve.
Nothing else can be better, if all your options are "mob rule" or "executive fiat".
I fancy myself a misanthrope, but damn, next to people in this forum I am probably the last humanist walking through the ruins of civilization.
> Deepmind is objectively good.
Google is objectively bad, and the world would be a much nicer place if they ceased to exist.
> I fancy myself a misanthrope, but damn, next to people in this forum I am probably the last humanist walking through the ruins of civilization.
A humanist who uses a term of sexual violence so cavalierly?
If you are in the United States and you want a good civic lesson in state power, you should go to your nearest metropolitan criminal court. Maybe you will have a more accurate view of what government means then. At the very least, you will likely learn to banish such a casual invocation of that word from your lexicon.
> Nothing else can be better, if all your options are "mob rule" or "executive fiat".
What we have now is the middle ground between king and mob. It took centuries and much carnage to achieve. Does the famous Churchill quote really need to keep being repeated? Do you have an alternative proposal? Or maybe you have a sensible proposal that falls within the established democratic bounds? Or perhaps instead by "would be a much nicer place if they ceased to exist" we should simply infer a generalized whining rather than any specific policy prescription?
What's your actual idea, do you have one?
Maybe if you endeavored to communicate without self-satisfied hyperbole you would find we actually have reason to agree with each other.
"You can *publish*, share and adapt output in accordance with the Terms, including the requirement to provide clear notice that (with the exception of the AVI Score) use is subject to AlphaGenome Output Terms of Use and of any modifications you make."
> , nor for any clinical purposes.
Of course they'll write this, there's no scoring tool that would advertise clinical utility unless they're charging you money
---
Your concern about publication is incorrect; they simply want you to cite them appropriately if you are indeed a researcher: https://deepmind.google.com/science/alphagenome/output-terms
I believe Google has been trying to improve their Streetview in coverage as apple has become a concurrent, but it still has the same bugs people have been complaining about for years (like going backward when pressing forward type of bad). If I remember correctly the bugs have been 'closed' or something before just to include it in the same slightly different way.
Looking at current hot problems, and exemplary of the situation: which public entities have endeavoured to backup the most important channels and videos from YouTube, the current historic video archive?
Why would I be grateful?! Because somebody did create those resources and made them available! And they did to common good (if anybody refused the expression "for" common good).
Every single serious theorist of democracy has recognized this.
Democracy is about rule of law and institutions, not simply the mob.
Tyranny of the majority is the paramount concern of all democracies. Nevertheless, institutions can fail.
The idea that democracy always leads to desirable outcomes is evidently false by historical record.
I just don't understand people who think the state is better than Google. Google pretty much works. Google does not have police powers. Google cant surround your car and point guns at your family. Most of the bad things about Google are actually forced upon them by the state. Who could have even a passing knowledge of history and think states are somehow safer than corporations?
Take the United States. Should Donald Trump get a say in how to run Google? Maybe you like him, so how about the guy that comes after him, or the next one after that?
The American mob seems intent on leading their country into the gutter. Good thing (despite what the mob has thrown at it) that the United States still has strong institutions and strong markets. Without Silicon Valley, America would have already lost its place on the world stage.
But please lets hear more indictments from a population who can't even agree with itself on the issues already under the government's purview. Now let's set a precedent for even more state interference in the market, that way when your party (whatever side you are on) chokes the next future election away the next nut you don't agree with has even more power? Is that your plan?
Trump does have a say in how to run google, in a very real sense.
> The American mob seems intent on leading their country into the gutter. Good thing (despite what the mob has thrown at it) that the United States still has strong institutions and strong markets. Without Silicon Valley, America would have already lost its place on the world stage.
American elites are more than happy to follow basically whatever Trump wants them to do with the knowledge that they'll get preferential treatment by the law and win all the no-bid contracts he can award. But ask yourself if this would be any different if Trump were head of a large company under a smaller regulatory state. Seems pretty obvious that not much would change.
If by "the mob" you mean, a small cohort of wealthy, powerful, unscrupulous people, those people who make decisions that the rest of us have no say in, then I agree, that is a problem.
> But please lets hear more indictments from a population who can't even agree with itself on the issues already under the government's purview. Now let's set a precedent for even more state interference in the market, that way when your party (whatever side you are on) chokes the next future election away the next nut you don't agree with has even more power? Is that your plan?
In a smaller state, Trump would have continued to be an executive and the shape of his impact on the world might be slightly different, but would be no less oppressive. Ask tenants in NYC in the 1980s if they think a Donald Trump with smaller regulatory oversight who stayed in business would be better or worse for our country.
Do you think our country flips parties every year because our government does a good job of reflecting the will of the people?
> Trump does have a say in how to run google, in a very real sense.
Indeed, as does every President or government. But surely, you have noticed and take seriously that he has acted with greater executive fiat? That by American standards, while he may not be totally alien, he is not "normal"? The question then is whether we want to accelerate along this trend. What is interesting is many populists, whether on the right or left, seem to answer in the affirmative, confident giving their preferred president increased power is the right trade to make. I simply ask, what happens when the government flips, as it always does? Then maybe you will come to regret your position.
> American elites are more than happy to follow basically whatever Trump wants them to do with the knowledge that they'll get preferential treatment by the law and win all the no-bid contracts he can award. But ask yourself if this would be any different if Trump were head of a large company under a smaller regulatory state. Seems pretty obvious that not much would change.
The first part of this is ahistorical. American elites always line up behind the President. If Kamala had won Zuckerberg would be out front with DEI or w/e. The big companies, banks, Silicon Valley, always shower money and gifts on the incumbent. The government operates in many ways as a big public/private partnership. Again, the danger with Trump is the degree, not necessarily a wholesale difference. Some people use this to say it doesn't matter, makes no difference. I'm not one of those people. I believe at a certain point, tip the degree too far, and a difference appears.
As for the second part, democracy allows the people to correct for their mistake. The elites did not want Trump, and never have. He came to power after descending an escalator, elites on both sides mocked him. Elites wanted to repeat Bush v Clinton. Trump may be wealthy, but he is not an "elite", he is new money, and has basically always been a joke among the upper echelons of power in New York City. The elites are nice to him because they are forced to deal with who the mob elected. To not do so is shareholder suicide. Everyone knows he is insane. They simply cannot say it out loud. And why would they? What's with people who simultaneously think Google has too much power and yet want them to be out in front fighting Trump? It's not their job. Why did the American people elect him? What is Google supposed to do? Ignore the President of the United States? Tell the American people who to vote for?
> If by "the mob" you mean, a small cohort of wealthy, powerful, unscrupulous people, those people who make decisions that the rest of us have no say in, then I agree, that is a problem.
No I mean the ~100,000 average Americans who actually make a difference in electing presidents, in places like Wisconsin, where the state is sufficiently purple and there is a small "swing vote" that is often well under a million people. When are they going to be held responsible for their mistake? Why is Google my enemy? I can stop using Google. Google provides me excellent services at a reasonable price (often $0 - I understand I give them data but who cares, really only the government would care about my individual data, and I know Google simply aggregates it to "subsidize" the numerous free services I get). So, a pretty fair deal, and one I can not enter to if I actually wish. On the other hand, what does someone in Wisconsin give me? I can't stop someone in Wisconsin from voting against my interests. Is Google supposed to be the tyranny here? Extend this same logic to any state on the wrong side of your preferred electoral divide. Like many Americans, I really have no say in Presidential elections, because I live in a populous, blue state. My vote doesn't matter, my electoral votes are already priced in. Meanwhile people in red flyover states get the same number of senators as my state, which has a multiple of their population. This makes corporations my enemy? Did Google sponsor the Connecticut Compromise?
> In a smaller state, Trump would have continued to be an executive and the shape of his impact on the world might be slightly different, but would be no less oppressive. Ask tenants in NYC in the 1980s if they think a Donald Trump with smaller regulatory oversight who stayed in business would be better or worse for our country.
Let's not move the goalposts. I never said I was against all government regulation. If you want to regulate Google, then fine. Make a sensible proposal. What is not serious nor sensible is saying "Google is evil" or "Google should not exist".
> Do you think our country flips parties every year because our government does a good job of reflecting the will of the people?
You need to not think only of the current case relative to your supposed best case, but also a worse case. What is the will of the people? Who decides? How? It seems obvious to me the government being defective is somewhat by design (separation of powers) because the founders knew as many people know now, that America is very large, very divided, and very dangerous. A federal government that doesn't give some of the voters 100% of what they want every four years is a lot better than another civil war. Yes things could be better. They could also be a lot worse.
I tend to think people who say "Google is evil" have a rather limited view of the downside risks that occur when humans congregate. Google does not even begin to scratch the surface of the historical depravities we have visited upon each other.
Have you been to states that predominantly vote against your particular preferred political party? You will find "the corporations" are not your enemy. It's what it always has been, all the time, throughout every historical age. The problem of civilization is other people. You will not get around that by trying to treat corporations as some special case.
Propose sensible regulations. Maybe even a way to reform the electoral college that has a chance of passing. I am interested in these ideas. Innovation can happen in technology and in government. That's why I like this forum. But too often interesting conversations are drowned out by "Google is evil" as if this is useful. I would love to hear more interesting solutions, and less hyperbole. Thanks for the pushback.
Solutions that worked for hunter gatherer civilisations 5000 years ago may no longer be viable, since they are incompatible with global supply chains.