pfisherman

Epigenetics is not just DNA, think of it more like the (hidden) state of DNA. Histone modifications and open chromatin and other epigenetic readouts are like emissions / indicators of the hidden state.

The relationship is like that between the words in a book and the page that is actively being read. I know that is a hackneyed analogy; but coffee is wearing off :)

RNA is an obvious example. The examples and benchmarks they give in the paper are not the straw men the DNA LLMs are beating the stuffing out.

Also CRE activity is highly cell type specific. This article is a pretty awesome demonstration of model guided design of cell type specific cis regulatory elements.

https://www.biorxiv.org/content/10.1101/2023.08.08.552077v1

An LLM would not be able to do this because DNA itself contains no contextual information about cell type - every cell has a copy of the full genome. Epigenetic tracks however contain a lot of information germane to the cellular context - ex which parts of the genome are being transcribed.

The article I posted shows what is working better - the Olga Troyanskaya / David Kelley style models. There was another one (Kundaje group?) recently that used Hi-C data.

Just gonna leave this here.

https://www.biorxiv.org/content/10.1101/2024.02.29.582810v1

Tl;dr: DNA is NOT all you need.

You did not have to scrape the pdfs using the website link. They have bulk downloads indexed by year (IIRC). I remember grabbing these because I had to OCR a bunch of summaries to extract data for some NLP I was running. Also, IIRC grabbing the predicates was pretty easy w/ tesseract.

> All of this nonsense is because scientists lost their moral standing by cheating, lying and going full woke

So Ozempic is just propaganda then? MRNA vaccines too? CRISPR? CAR-Ts? LLMs? EV Batteries? Nike Alpha Flys? Superconductors?

Hate to break it to you, but we are in a golden age of science especially in Biotech.

Nature and Science are kind like the tabloids of scientific publishing. Legitimate news mixed with unsubstantiated gossip; all with a high “sexiness” factor that draws attention and moves copy.

Obvious satire; and not particularly good or funny satire either. It tries too hard to be offensive and transgressive without really pulling it off. Like a parody of Google / Silicon Valley corporate speak written by someone who is not fluent?

I know! Who has ever thought of Americans as a particularly refined bunch? I know that we don’t think of ourselves that way.

No. In general there are many orders of magnitude more variations throughout the genome than there are observable phenotypes. We don’t know what genes most cis regulatory elements regulate; and we don’t know what most genes do in which contexts. Hell, we don’t even know how many different types of cells there are in the human body.

> Consistent across performances and devices

LOL! I think the assumption that an ML system would be robust across these contexts is not well founded. Things as innocuous as the lighting, background, or placement of athletic tape could easily wreck a model like this.

The thing about human judges is that the modes of failure are pretty well known at this point; and human perception and visual processing is pretty robust to perturbation.

I did not say or suggest that his actions were justified.

My point(s) is that he was relatively “normal” high functioning autistic guy, who ended up in an intense situation that he did not have the social / emotional / cognitive tools to deal with, and started acting erratically. The whole thing is a damn tragedy.

It is easy to point fingers and divide the world into the good guys and the bad guys. But the truth is that anyone is capable of almost anything under the right circumstances; and we never really know how we will react in extreme situations until we are in them.

Read the details of the case.

Did they diagnose people with high functioning autism back in the 60s and 70s? Was Asperger’s even refinished as a thing back then? I don’t know for sure that he got a diagnosis. But was pretty obvious to all in the neighborhood in retrospect.

Anyway, I shared my perspective as someone who was a little closer to the whole episode than most. Perhaps there are some details in there that did not make the Wikipedia page. You are free to discount it or not. Ain’t a thang to me.

He freaked out in the midst of an acrimonious custody battle. I don’t know if you know or have been close to anyone who has gotten divorced; but people can stop thinking straight when their kids are involved.

This guy is what a mean bully looks like.[1] Crossed paths with him when we were kids and I am not at all surprised he ended up where he did.

1. https://www.justice.gov/archive/opa/pr/2005/February/05_crm_...

I grew up down the street from Hans. I did not know him well, as he was the age of my older brother. I remember they worked on a couple of teenage electrical engineering projects together. Some of the filtered down to me. Hans was autistic and had the mind blindness thing going on, which sometimes made social interaction difficult for him. I think that most of my family did not want to believe that he killed his wife; and that some of his bizarre behavior could be explained by just not having that instinct that drives people to conform to social norms. But once he led police to the body the realization set in for us. Maybe we were the last know.

Our understanding was that it was a crime of passion - a heated argument over custody of children. He was not mean, evil, or a bully or anything - growing up in Oakland I have met a few of those. He is someone who lost it and made a really bad decision that ended a life and destroyed his family. I wonder if things might have turned out differently for him if he had been born 20 years later when there was more awareness and resources for neurodivergent people.

Don’t discount people’s capacity for self deception. We all want to be the hero of our own story.

In any event we are judged by the totality of our actions, not a subset of our beliefs. Hitler was a vegetarian who wanted to ban smoking.

Really?!

She is one of the people most directly responsible for building Facebook into a massive surveillance / influence / control monstrosity and monetizing their abuses of their user base; and your problem with her is that she is an unabashed feminist?!

I think the replacement of SROs by luxury apartments in downtown SF (mid Market neighborhood) was an under appreciated driver of homelessness there. This was housing of last report for many.

Is the Hollywood trope “Leave It To Beaver” or “Revolutionary Road”?

Were marriages happier in the 1950s? Or were people just trapped in unhappy marriages without any recourse?

Weren’t many of the 1950s housewives taking amphetamines and antidepressants to cope?

Putting some effort into (3) can increase your citations (h-index). If people can’t use your software then they will just find some other method to benchmark against or build on.

Here you are not improving your time to get out an article, but reducing it for others - which will make your work more influential.

The university brass showed up to a reality tv show thinking that it was going to be a PhD defense.

If I were doing their media prep, I would tell them to just ignore the questions and launch into fiery monologues about freedom of speech, liberty, American values, etc instead. Maybe accuse one of the unfriendlies of antisemitism and political grandstanding.

> They can prescribe a drug which is not FDA approved, can they?

Yes they can. They can give you whatever medical advice or prescribe whatever regimen they want. They could tell you to drink bleach and the FDA would be powerless to do anything about it.

I think the strongest argument for you would be a drug approved in another country; but not in the US. Your doctor can still prescribe it; and under the right conditions that prescription can allow you to obtain the drug in a foreign country and bring it back to the US.

https://www.fda.gov/consumers/consumer-updates/5-tips-travel...

Sorry, I do not quite follow. FDA regulates the marketing of drugs, biologics, medical devices, etc. They do not regulate the practice of medicine. Your doctor can prescribe whatever they want “off label”.

So for example, manufacturers cannot market erbitux as a cure for migraine headaches because no sponsor has submitted an application to FDA with compelling evidence that it is safe and effective for that particular indication. However, your doctor can still prescribe it for migraines if they so choose. Whether your insurance will pay for it is a different story.

I had the opportunity to get a peek at the FDA database of adulterated supplements and by far the most common type of adulteration was people spiking with viagra. I asked why and was told:

“Man has been searching for an aphrodisiac for thousands of years and we finally found it. Of course they are going to put it in everything!”

They do not for supplements. Supplements fall under the office of the Director, which is not funded by PDUFA / MDUFA. Supplements are basically the Wild West.

Well I assume that GP wasn’t around for the dot com bust or 2008.

“We are all ready to win, just as we are all born knowing only life”

- Han (Enter the Dragon)

Chemprop is not new, it has been around since at least 2020.

The headline is sensationalized.

They did a virtual screen of a large compound library.

QSAR / QSPR / Virtual Screening has been around since the late 1950s.

The secret sauce here was the large experimental dataset - on the order of 10^5 compounds - they generated to train the model.

Maybe the explainability part is kind of novel for a neural network based approach; but not clear that you couldn’t identify substructure classes better with a pure bioinformatic approach.

Get ready to see vaccines be used to prevent and cure conditions you that you probably think are outside the scope of what vaccines can address.

Projecting further into the future, the world is going to be divided into those with access to and willingness to use biotechnology and those who don’t. Note that I am including things like fitness and health tracking apps under the umbrella of biotech.