This is so friggin cool. You don't have to rewrite all that FORTRAN to do autodiff on it. "Enzyme"

When a T cell carries both its natural TCR and an engineered CAR, do these two receptors cooperate - or compete? Our new preprint on bioRxiv shows that TCR activation can enhance CAR-T activation but impairs CAR-mediated killing when targets are on separate cells. www.biorxiv.org/content/10.1...

No Distinct Gut Microbiome Signature in Alzheimer's Disease: A Reanalysis with Modern Tools https://www.biorxiv.org/content/10.1101/2025.09.09.675220v1

Now out in @natmachintell.nature.com TCRT5 is a rapid generator of target-conditioned CDR3b, leads SoTA, and yields the first AI-designed self-tolerant binder to an OOD non-viral epitope (w val) 📑: www.nature.com/articles/s42... 🤗: huggingface.co/dkarthikeyan1 👨‍💻: github.com/pirl-unc/tcr_translate

tl;dr T5 style translation model to generate T cell receptors from targets actually kinda works Caveats: not full TCR (CDR3b), strong signal that public data biased towards “polyspecific” TCRs — lo and behold, generated TCR-T is polyspecific in vitro. Open weights, go wild.

With some key contributions by Sarah Bennet in actually turning predicted TCRs into TCR-Ts and testing them! Hopefully this raises the bar on TCR generation evals, I think we the best in silico metrics and 1 in 20 TCRs just kinda works.

This is a cool story that I've watched with great interest - making big steps in the field of de novo TCR generation! Great work @dkarthikey1.bsky.social / @benjamingvincent.bsky.social / @alexr.bsky.social et al

Today’s news about Joe Biden makes it almost difficult not to reflect on the unrealistic promises from AI leaders who claim AI could end disease and usher in radical abundance. Disease will persist. AI is a tool, not a cure-all. People deserve truth, not hype. www.cbsnews.com/amp/news/art...

NSF to ONLY fund research in five areas: artificial intelligence, quantum information science, biotechnology, nuclear energy, and translational science. Can this be happening? www.science.org/content/arti...

what do you teach at the first-year graduate course on machine learning, in this era of LLM and large-scale compute? here's my experiment on answering this question: let's teach everything that admits SGD and that is not LLM, and ask students to read old papers.

We hadn’t won World War II by May 8th. I know because my family and I were still in an internment camp in Tule Lake, California.

Your immune system gradually loses it top team players when we get older 👱➡️👵 Our study in @ebiomedicine.bsky.social investigates how long good immune cells stay around – a 🧵⬇️ go.unimelb.edu.au/4sep @katherinekedz.bsky.social @thedohertyinst.bsky.social #Influenza #AgingResearch #Immunity #TCR

My PhD student's NSF grant was terminated today. Her dissertation investigates why air pollution monitoring, metrics, and regulations don't properly capture the harms experienced by marginalized communities--esp in the most polluted Detroit neighborhoods. She and I are happy to talk with press etc.

I am so excited to share that our new paper is out! A model of intratumor and interpatient heterogeneity explains clinical trials of curative combination therapy for lymphoma Out in Blood Cancer Discovery doi.org/10.1158/2643-3230.BCD-24-0230 #mathonc #lymsm #BloodCancer 1/n

Do you analyze large BCR and TCR sequencing datasets? Answer our survey for improving nf-core/airrflow, a Nextflow pipeline to analyze bulk and single-cell AIRRseq data (doi.org/10.1371/jour...). We’re interested in your opinion on useful new features! yalesurvey.ca1.qualtrics.com/jfe/form/SV_...

HHS's Office of Long COVID Research and Practice has been DOGEd. Closing this week.

We @prescientdesign.bsky.social Genentech pre-printed our "Lab-in-the-loop for therapeutic antibody design." We built a general ML system to accelerate molecule design for challenging, therapeutically relevant targets. www.biorxiv.org/content/10.1...

You in the Triangle area and thinking about standing up for science? Come to my beloved 2nd workplace and make a sign 😊🍻 supplies provided! You can leave a sign w me and i can bring it up to DC! @standupforscience.bsky.social

Dear TCR researchers of #immunosky, you may be interested to know that our tool Stitchr - for the automated production of full-length T cell receptor sequences - has just had a nice little update: jamieheather.github.io/stitchr/

🚨BREAKING. From a program officer at the National Science Foundation, a list of keywords that can cause a grant to be pulled. I will be sharing screenshots of these keywords along with a decision tree. Please share widely. This is a crisis for academic freedom & science.

Musks method of ruthlessly enforcing efficiency by removing things and adding them back if the system breaks has worked well for pruning complexity of products, pipelines and entire companies. But applying this methodology to govt is dangerous and will result in greater harm to the American people

Good combo! A nasal vaccine with self-amplifying RNA (much less dose required for v potent immune response), complete protection effective vs both H5N1 and H7N9 viruses in experimental models www.biorxiv.org/content/10.1...

On the merits of reading papers, attending conferences, preprinting manuscripts… Overseen at the Library of Congress.

Unsure if people on bsky are aware of o3s existence. But if anyone wants to talk I’ve been itching all day

How to learn generalizable rules across complex sequence-function maps? 💡In our new preprint we propose a framework for learning two-point statistics and use it to discover biophysical rules of TCR co-specificity that generalize to unseen ligands ! ✨ arxiv.org/abs/2412.13722

Ideal test is antibody CDRH3s which often conformationally rigidify during affinity maturation. MSAs only report inter-species evolution, not intra-species maturation, so existing methods fail. Pics from doi.org/10.3389/fimmu.2018.03065 & doi.org/10.3389/fmolb.2020.00182

Given the subtext here I wouldn’t be surprised if both X and Bsky develop extremely close but distinct niches: the former to blast information and reach broader audiences, and the latter as a place of discourse with members of a particular community.

🧙🪄Summoning Alex to 💙🦋 so the Bio x ML community can celebrate ESM-C with him on here as well

My usual go to is VDJdb. Set antigen species to human, minimal confidence score to 3, and paired A+B. It's not perfect, but it filters out most of the cruft. There's also a new DB called TRAIT which has a nice pack of TCRs that are being/have been trialed, which are mostly against human epitopes.

CA Coworking 🌉🌅

Calling all T-cell aficionado's. Come and join us next year (27-28 May 2025) for the fourth Antwerp T-Cell Receptor conference organised by @pmeysman.bsky.social, @krislaukens.bsky.social and Benson Ogunjimi. I'll also be there! www.uantwerpen.be/en/conferenc... #ImmunoSky

#GoodThingsComeToThoseWait Sorry it's taking us a while. Promise that the wait will be well worth it! #OpenFold3 Love all the great work that's already been done #HelixFold3 #Ligo #Chai1 #Protenix #Boltz1

Surely I misheard. There’s no way Dr. Oz, the OG grifter, president of grift university, has been tapped to lead the largest and most influential US healthcare entity.

My first Skeetorial! 💻🧬TCR-TRANSLATE - A new framework for thinking about the TCR:pMHC specificity problem. TLDR: We pretrained LLMs on ~8M TCR & pMHC seqs Finetuned on sparse pMHC->TCR pair data Validated CDR3b sequences to unseen antigens >> random performance on IMMREP2023 "private" antigens

TCR-TRANSLATE: Conditional Generation of Real Antigen Specific T-cell Receptor Sequences https://www.biorxiv.org/content/10.1101/2024.11.11.623124v1

LLMs are fantastic learners of arbitrary sequence to sequence mappings. Text summarization, Q&A, and machine translation, etc. So what happens if you apply them to the many-to-many mapping of the TCR cross reactivity landscape? Turns out, some pretty cool things. Check it out 😏

The fate of this app hangs in the balance tonight…

Load-based divergence in the dynamic allostery of two TCRs recognizing the same pMHC https://www.biorxiv.org/content/10.1101/2024.10.16.618634v1

Someone should do an autopsy on Twitter. When did it stop being Twitter? I know it’s easy to point at Elon but what really happened? Beyond the obvious what second order phenomena can be traced to its decline? 3rd/4th?

Insane finding: repeat covid infections result in milder symptoms but a greater propensity for long-COVID. Something really interesting is going on here and I want to know if it’s T or B cell mediated

What other keywords should I add to the MLSky feed? It's a tricky balance -- something too technical never triggers but eg #llm #chatgpt even "PyTorch" &c get mostly spam

It appears that my peoples (scientists) are preparing for a mass migration back onto here come election szn so whattup fam, I’m back

Back on here because I’m noticing a dangerous trend on Twitter where among other things bot engagement is being used to silence organic activity, particularly on controversial matters. Gonna try to use my codes to bring people on here as voting szn draws near.

Totally legit question for all the PIs on here: when working on a problem that has a lot of other people publishing on it, how does one write an introduction that doesn’t sound like a paraphrasing of 20 other papers 😩

The UNC Genetics Dept / BCB / GMB retreat was this week in Asheville NC and it was stellar. These two students from @alexr.bsky.social lab gave a hilarious and emotional rollercoaster of a presentation about getting scooped and still pulling through. Poster sessions and talks were all 👌

"The Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design" "A fully-remote, biennial competition for the development and benchmarking of computational methods in protein engineering" Hope you'll all participate! arxiv.org/abs/2309.09955

There are few pleasures in life that will even come close to enjoying chai and reading papers by a window in the rain 😌

I’m looking for a man/machine that goes by Alf…