Decoding immunity. Autoimmunity is far more common than anyone today expects or understands. CSO @cdi_labs

Oregon
We haven't even begun to collect the training data needed to find the cause and cure of autoimmune-induced chronic disease.
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Nearly time to build “the human autoantibody project”
you should start a biology research institution going after your own personal millennium problem. there has literally never been a better time
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A ton can be done with today’s tech on low hanging fruit but the “true” scope of autoimmunity is the proteome x all-possible chemical transformations thereof and imagine it’ll be decades before we get into all the nooks and crannies.
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A tour de force paper all to show: One aberrant immune response to one peptide --> One 'complex' chronic disease I am ever more convinced most 'complex' chronic diseases are this simple (and impossible to cure without decoding antigen-specific autoimmunity).
Universal seropositivity, markers of recurrent reactivation, and a convergent T-cell response implicate cytomegalovirus in Susac syndrome researchsquare.com/article/r…
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Tyler Hulett retweeted
Replying to @ChrisHayduk
My daughter has an ultra-rare, autosomal dominant, monogenic neurological disorder with fewer than 200 cases worldwide. It is characterized by haploinsufficiency; however, unlike some genes underlying other genetic diseases, the affected gene is too large to fit into a standard AAV vector for a gene therapy intended to deliver neurons a working copy. I am using GPT-6 Astra and the Rosalind Workbench to design candidate minigenes for my daughter (and others affected) that are sufficiently sized for viral delivery while retaining the most important functional domains of the protein. The idea of minigenes has precedent: Elevidys by Sarepta Therapeutics is FDA approved for Duchenne Muscular Dystrophy and consists of a “micro-dystrophin” transgene about a third of the size of the wild type dystrophin. Specifically within Rosalind I am using the Biological Sequence & Alignment Viewer, Biohub ESM plugin (for folding candidate minigene variants and domains), and the Molecular Structure Viewer (for alignment to the wild-type reference predicted structure). Furthermore, I am leveraging additional databases like ClinVar to cross-reference pathogenic missense variants that suggest regions critical to functional activity, since little is known about the disease in general. I would be exceptionally thankful for the additional credits of the Pro plan as I keep quickly running out of usage, and this is a use case where I most certainly want the best available model.
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Decoding bad antibodies is the way to fix many diseases
Did you know a discovery made during malaria research could someday help people with alpha-gal syndrome? In this video, I share how NIH researchers identified rare antibodies that may help prevent allergic reactions associated with this tick bite-linked condition. It's a great example of how research can lead to unexpected discoveries with the potential to improve lives. Learn more: bit.ly/4cnX4Z5
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Absolutely love that my projects shut down whenever Astra or Opus notice public UniProt virus sequences in my database.
Taking viral genome sequences off public databases does ~not~ reduce risk of synthetic viral pandemics by >90% Information hiding will not reduce security risks — the only thing that will actually work is vastly improving our technological capabilities that allow us to produce effective countermeasures with rapid response Obfuscation is not a meaningful security strategy, as we've learned from decades of cybersecurity practices. It only serves to harm defensive efforts and slow our ability to craft responses Also see the history of things like Napster and Limewire, pirate bay, Library of Genesis, torrents, etc; Information cannot be prevented from being shared through the world. Attempting to obfuscate it will only harm beneficial defensive efforts
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Jenner cured smallpox blind to the mechanism. We cannot predict who will respond to Allison’s anti-CTLA4. But to move faster - we need more data.
taps sign most of the data AI needs to predict human biology doesn’t exist yet.
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Oh wow you trained 140k model fruit fly neurons to play beat saber? How about the trillion plus immune cells (without literal physical contacts to map) - in one person? In you specifically? Undoing their mistakes to fix your chronic disease? Lol, lmao even.
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Tyler Hulett retweeted
This is legitimately terrible for OpenAI --- but also Anthropic --- and it relates to their work in drug discovery. I read this as: prompts will be monitored and potentially acted on if we think there’s something scientifically and/or commercially valuable being disclosed. Now, the big problem for Anthropic is that they are increasingly seen to be competing with their customers. Outside of SF, many people also think of OpenAI/ChatGPT and Anthropic/Claude as somewhat interchangeable companies and products --- aka, if OpenAI do something, surely Anthropic will do it too? As so much IP relates to drug targets and people disclose these to Claude, I think we will see a lot of pharma companies stop using these tools or put up a lot of internal guardrails.
wtf is this way to handle mathematicians work and scientific communication TLDR: Leven and Tristan worked over several months on one of the Millenium Prize Problems with various AIs to reach final interesting results. OpenAI apparently heard about it in the last days and prompted their latest models to work on the direction Leven and Tristan found fruitful. They then tried to push for controlling communication of the result and dropping Leven from authorship with some very bad taste social pressure. Hope this is not a glimpse of the future we’ll get in science research with these dominating players playing marketing games hurtful for the real scientific community.
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Even more are obese - often blamed on the afflicted vs true root causes.
A generation of young, previously healthy people are deteriorating with severe acquired brain dysfunction. Labeling this as “brain fog” erases severity, obscures biology, and delays recognition of true neurologic injury characterized by neurovascular and metabolic derangements.
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Brain fog, metabolic syndrome, ME/CFS, multiple sclerosis -- look to immunity for your mechanisms. Be it aberrant to a virus, bacteria, or transformed-self. Autoantibodies targeting AGE-modified glucagon, insulin, VIP, etc produced after glucose-heavy meals under PUFA body comp?
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^Would explain 'why keto works' for obesity AND low fat high carb. 'The linoleic acid makes the carbs dangerous and obesogenic (sometimes).' And why obesity + specific diet cures are selectively penetrant, age-associated, exercise ameliorated, altitude associated, etc
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Automated colony picking 🤯
Beep boop bop, engineered the singer PIXL colony picker into a python library, and have Claude operate the machine (gonna PR to @pylabrobot when I can) Fully automated yeast engineering here we come
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What humanity is able to observe is defined by the instruments available to make those observations. This robot is building "a telescope" that will help observe types of autoimmunity never-yet looked for and create a more complete synthetic human proteome.
96-plasmid yeast transformation and 384-spot plating across 4 SBS agar plates for clonal purification. solved by @pylabrobot in 3.25 hours rfc.geneticassemblies.com/rf…
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Unlike a telescope you can point anywhere in the sky - you need to have a library of 'possible targets' to discover novel immune diseases. And people like @koeng101 @_benray make it possible to make them. Some of those proteins were just discovered:
Introducing peptidiens! Congratulations to the TransCODE consortium on this exciting tour-de-force in @Nature: nature.com/articles/s41586-0… We look forward to seeing what’s next as lead authors Sebastiaan van Heesch (@prinsesmaximac and @oncodeinstitute) and John Prensner (@UMich) take on our dark proteome challenge as part of team ILLUMINE! Team ILLUMINE is funded by @CR_UK, @theNCI, and KiKa (Children Cancer Free Foundation) through Cancer Grand Challenges
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Anyone have tips for getting on 'trusted scientists lists'? Have never been able to use Fable, worried I won't be able to try Astra. My 'decoding molecular mimic origins of autoimmunity app' gets flagged whenever the agent sees 'variola' in the pan-viral database....
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Goal is aligning sequence level antiviral and autoantibody data en-masse to automate at-scale discoveries like this....
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Tyler Hulett retweeted
seems like the general timeline to get medicine to stop making an active mistake* is ~25 years * eg, autologous bone marrow transplants after total body irradiation for cancer treatment (oops cancer cells hiding in there), anti-menopause hormones, "have you tried losing weight?"
Doctors X-rayed pregnant women routinely in the 1950s to check which way round the baby was lying. Nobody thought it was dangerous. Alice Stewart noticed childhood leukaemia rising sharply in Britain and set out to find why. She and her team interviewed the mothers of 1,400 children who had died of cancer, and 1,400 mothers whose children were alive, and asked them the same questions. The pattern showed up in the first 35 pairs. Children who had died were about twice as likely to have been X-rayed in the womb, and a single scan at the dose used then appeared to be enough. She published in 1956, and the response was outrage. Radiation was the technology of the future in the 1950s, and the claim that a low dose could cause cancer years later contradicted what the entire medical and nuclear establishment believed. Her methods were attacked. Her funding suffered. Doctors carried on X-raying pregnant women. It took roughly 25 years for the medical world to come round. Pregnant women were still routinely X-rayed into the late 1970s. Two decades after she told them to stop. She retired in 1974 and did her most contested work afterwards, in her seventies, examining the health records of American nuclear weapons workers. Her findings there were unwelcome enough that the Department of Energy cut off her access to the data. She spent 14 years fighting them and testified before Congress, and in 1990 the records were opened to independent researchers. She died in 2002, aged 95. The children who were never X-rayed have no idea who she was. history.rcp.ac.uk/blog/alice…
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Doubt many highly-immunogenic tumors (melanoma especially) can exist without an error of immunity (inherited defect or acquired autoantibody).
I guess B cells really suck…we should kill them in autoimmune patients and now they are saying in #cancer patients too!! Seriously ?? jci.org/articles/view/205606
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Could enable elegant, controlled autoantibody discovery to carefully selected neo-self PTM structures. Imagine rather than citrillunating or AGE-transforming a full PhIP-Seq library - you integrate transforms JUST at controlled sites via engineered translation.
Interesting work by George Church et al. In Nature, Nature Portfolio @geochurch @Nature nature.com/articles/s41586-0…
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