Seth Howes
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on the atlas · 28
- Practice (learning method)1 savers
- Evo 2 Can Design Entire Genomes3 savers
- A socratic dialogue over the utility of DNA language models (Part 1 of 2)1 savers
- Notes on creative context1 savers
- Genome in a Bottle | NIST1 savers
- Niko McCarty1 savers
- A Visual Guide to DNA Sequencing1 savers
- Making the Vortex Mixer1 savers
- How to Start a Startup3 savers
- Before the Startup5 savers
- Galápagos syndrome3 savers
- Netflix and the Conservation of Attractive Profits – Stratechery by Ben Thompson2 savers
- Grimes: nine days without food, sleep or company gave me Visions | Music | The Guardian1 savers
- The Electric Slide - by Packy McCormick and Sam D'Amico1 savers
- Hub-and-Spoke Biotechs: BridgeBio - by Elliot Hershberg1 savers
- AI Versus Eroom's Law - by Elliot Hershberg1 savers
- Wearables Mostly Don't Work - Cremieux Recueil1 savers
- Advanced Research Projects Agency for Health1 savers
- Variant of uncertain significance1 savers
- Personal genomics1 savers
- Inside the stealthy startup that pitched brainless human clones | MIT Technology Review1 savers
- Disruptive innovation1 savers
- The Inside Story of the Greatest Deal Google Ever Made: Buying DeepMind - WSJ1 savers
- Self-experimentation in medicine1 savers
- Quantified self1 savers
- Personal Science1 savers
- The strength of weak ties | Stanford News1 savers
- Don’t Let Architecture Astronauts Scare You – Joel on Software1 savers
highlights · 92
According to Ericsson, a practice session needs to follow these criteria in order to be considered "deliberate": The task should be well defined, with a clear goal, and should be completely understood by the student. The student should be able to do the task by themself. The student should be able to access immediate feedback about their performance, so they can make the changes needed to improve. The student should be able to replicate the tasks or similar tasks repeatedly. The task must be designed by a teacher and must be performed following a clear instruction by the teacher.[19]
Practice (learning method)short snippets of real, human mitochondrial DNA and asking the model to extend the sequence into a full-length genome.
Evo 2 Can Design Entire Genomesspend months trying to figure out whether a genetic mutation causes disease
Evo 2 Can Design Entire GenomesGiven how closely PhyloP got to Evo 2 in the above BRCA1 variant prediction benchmark
A socratic dialogue over the utility of DNA language models (Part 1 of 2)multiple sequence alignments (MSAs). You take a bunch of genomes from different species, align them, and then see how often each nucleotide changes
A socratic dialogue over the utility of DNA language models (Part 1 of 2)We still probably need to do those enhancer screens and chromatin assays, but at least we can start off with a prioritized list of genomic regions to target.
A socratic dialogue over the utility of DNA language models (Part 1 of 2)the SHH (Sonic Hedgehog) gene is controlled by an enhancer called ZRS, which is one million base pairs away from the gene itself. If you delete or mutate ZRS, you can get serious developmental disorders like polydactyly (extra fingers and toes), even though the SHH gene itself remains perfectly intact. Evo 2 would likely pick up on this.
A socratic dialogue over the utility of DNA language models (Part 1 of 2), PCSK9 inhibitors were discovered as a result of an unusual genetic variant someone found
A socratic dialogue over the utility of DNA language models (Part 1 of 2)‘impact' to be equivalent to ‘variant discovery that is directly impactful for human health’
A socratic dialogue over the utility of DNA language models (Part 1 of 2)most genetic risk is blurry, probabilistic, and fundamentally hard to act on.
A socratic dialogue over the utility of DNA language models (Part 1 of 2)we know the schizophrenia is highly heritable, but we haven’t been able to nail down the genetic basis for it. We know that heart disease has a strong genetic component, but outside of a few well-known risk alleles (like in PCSK9 or APOE), most of the heritability is tied up in thousands of tiny effect variants that we don’t fully understand. And for neurodevelopmental disorders like autism, we’re pretty sure genetics is a huge driver, but no one has a good map of how it all works.
A socratic dialogue over the utility of DNA language models (Part 1 of 2)The pre-cached answer is that this ‘consumer being aware of a disease earlier than expected’ thing is more impactful than you’d expect
A socratic dialogue over the utility of DNA language models (Part 1 of 2)If the mutated DNA likelihood is much lower (unexpected) than the normal one, they interpret that as a loss of function of BRCA1
A socratic dialogue over the utility of DNA language models (Part 1 of 2)Traditional pathogenic variant annotation rely pretty heavily on conservation scores, like PhyloP
A socratic dialogue over the utility of DNA language models (Part 1 of 2)does mean evolution hasn’t had the chance to vet it yet. Which also (probably) implies that it is, indeed, bad.
A socratic dialogue over the utility of DNA language models (Part 1 of 2)If you have a model that has a really good latent understanding of DNA sequences, you can…do what exactly?
A socratic dialogue over the utility of DNA language models (Part 1 of 2)I ship something small and gain confidence from it and switch back to the big project.
Notes on creative contexthe started getting invited to dinners, lunches etc. They seemed like modest commitments, but somehow he found he couldn't make any progress on his next novel
Notes on creative contextStephen King says he never takes a day off writing, including Christmas and birthdays
Notes on creative contextcreative people often work so monomaniacally on things. It keeps them in the creative context
Notes on creative contextprompts: "I am scared that…" "The problem I'm having that I don't want to think about is…" "The incredible opportunity that I'm shy to think about is…" "I fucking hate…"
Notes on creative contextread aloud on adjacent subjects, especially in inspiring material.
Notes on creative contextBlocks – staleness or stuckness or procrastination – are signs you've disconnected from your creative context:
Notes on creative contextSomeone would look at him wrong at halftime, a quick glance or comment. And he'd use it as motivational fuel – sometimes for years!
Notes on creative contextcreating powerful motivating contexts
Notes on creative contextwhile ideas ultimately can be so powerful, they begin as fragile, barely formed thoughts, so easily missed, so easily compromised, so easily just squished
Notes on creative contextBefore Taq was discovered, scientists were forced to add “fresh” polymerase to their tubes during each cycle, manually moving them between water baths held at the three different temperatures.
Niko McCartySometimes you sit down, intent on making a specific argument, only to find (upon deeper research) that the argument is garbage and doesn’t hold up to scrutiny!
Niko McCartyzero-mode waveguides (ZMWs): small containers just big enough to hold a single DNA polymerase and containing tiny holes at the bottom through which light could be detected
A Visual Guide to DNA SequencingSequencing by synthesis requires repeated amplification, which introduces the possibility of error at each step and biases outputs towards sequences readily amplified by DNA polymerase
A Visual Guide to DNA Sequencingfirst commercial product in 2015: a handheld machine called the MinION
A Visual Guide to DNA Sequencinglow the DNA down to detectable speeds, using the familiar DNA polymerase enzyme. Mark Akeson’s lab at UC Santa Cruz had identified a specific polymerase from the bacterial virus ɸ29 that replicated DNA at an ideal speed for detection via nanopore
A Visual Guide to DNA Sequencingengineered nanopore developed in collaboration with Bayley’s lab that could discriminate between individual DNA bases
A Visual Guide to DNA SequencingONT quickly brought together various technologies, licensing IP from the labs of Bayley, Deamer, Branton, and others.
A Visual Guide to DNA Sequencing1996, David Deamer and Daniel Branton’s
A Visual Guide to DNA SequencingThe first nanopore used for sequencing was ⍺-hemolysin, a protein toxin from the bacterium Staphylococcus aureus
A Visual Guide to DNA SequencingStanford ELITE study,
A Visual Guide to DNA SequencingIn the mid-1990s, University of Cambridge biochemists David Klenerman and Shankar Balasubramanian were trying to solve a fundamental problem: how to watch a single DNA polymerase molecule at work. Their approach used modified nucleotides, called reversible terminators, tagged with four different colors of fluorescent molecules. If one of these “terminators” was grabbed by the DNA polymerase and incorporated onto the replicating DNA strand, it would block the addition of any other bases until removed using a separate chemical reaction. Klenerman and Balasubramanian’s great insight was that temp…
A Visual Guide to DNA Sequencingthat distinction went to Connecticut-based 454 Life Sciences, who licensed whole-genome pyrosequencing applications in 2003
A Visual Guide to DNA SequencingJack brought the original idea to Harold, and the two sketched out potential solutions on October 20, 1958. Just three days later, they had built their first prototype using the same kind of shaded pole AC motor found in their record players.
Making the Vortex MixerUnless you're in a market where products are as undifferentiated as cigarettes or vodka or laundry detergent, spending a lot on brand advertising is a sign of breakage.
How to Start a StartupThey're the more strategically valuable part of the market anyway. In technology, the low end always eats the high end. It's easier to make an inexpensive product more powerful than to make a powerful product cheaper. So the products that start as cheap, simple options tend to gradually grow more powerful till, like water rising in a room, they squash the "high-end" products against the ceiling
How to Start a StartupA 10% improvement in ease of use doesn't just increase your sales 10%. It's more likely to double your sales.
How to Start a StartupDon't force things; just work on stuff you like with people you like.
How to Start a StartupAnother sign of how little the initial idea is worth is the number of startups that change their plan en route. Microsoft's original plan was to make money selling programming languages, of all things. Their current business model didn't occur to them until IBM dropped it in their lap five years later.
How to Start a StartupWas the person genuinely smart? If so, could they actually get things done?
How to Start a StartupOne of the best tricks I learned during our startup was a rule for deciding who to hire. Could you describe the person as an animal?
How to Start a StartupSo here is the ultimate advice for young would-be startup founders, boiled down to two words: just learn.
Before the Startupmaintaining design leadership without manufacturing leadership is not a coherent strategic position, and one that gets less coherent the better you believe AI will get.
The Electric Slide - by Packy McCormick and Sam D'Amicoinstead, the processor itself has to be modular and conformable
Netflix and the Conservation of Attractive Profits – Stratechery by Ben Thompson