T cells do the heavy lifting when it comes to the anti-tumor action of checkpoint immunotherapy. But do antibodies play a role too? That’s the question @yile_dai looked to answer in his thesis work, out today in @Nature! 🧵below nature.com/articles/s41586-0…

"[B]onferroni may roll in his grave but i will be vasodilated." 🤣🤣🤣 Frame it- certified banger.

My feed has been nothing but Anthropic hate for the past 24 hours. Good. Although I favor open source, proprietary models don't offend me so long as people can actually use them. The real motivations for nerfing the best use cases for AI like bio are obvious and insulting.

👇Learn more about our efforts to bring forward a best in class #TCR targeting a hitherto undruggable target... p53 (R175H)... presented at this year's #SITC Spring Scientific meeting💉🧬. @sitcancer @parkerici @GormallyMDPHD #Tcellpower. ondemand.sitcancer.org/media…

A holy grail for our lab has been tracking myeloid cells in human tumors in the same way that we track T and B cells with TCR/BCR. @vincentzliu and @CalebLareau solved it! We developed Mitotrek using scATAC-seq mitochondrial DNA to do exactly this. Using Mitotrek, we find that new myeloid cells clones constantly infiltrate the tumor via circulating monocytes — and that their macrophage or dendritic cell fate is epigenetically programmed before tumor entry. @10xGenomics @parkerici @CancerResearch @TheMarkFdn cell.com/cancer-cell/fulltex…

We’re excited to share the full binder design protocol. Check it out here: github.com/Biohub/esm/blob/m…. The notebook includes support for @modal to easily scale up binder generation. Give it a try and let us know how it works! You can read more about ESMFold2, ESMC, ESM Atlas, and the full results in the paper here: biohub.ai/papers/esm_protein….

Today we're announcing ESMFold2, an open scientific engine to power prediction, design, and discovery across protein biology. The new model delivers state of the art performance on protein interactions, especially antibodies, a critical modality for therapeutics. We have designed and validated miniprotein binders and single chain antibodies across five therapeutic targets that are important in cancer and immunology. We are seeing very high success rates, and affinities at levels consistent with therapeutic activity. We’re also releasing an atlas of 6.8 billion proteins, and 1.1 billion predicted structures. ESMFold2 is built on a state of the art language model that has been trained on billions of protein sequences. A world model of protein biology emerges through language modeling. We’ve used the techniques of mechanistic interpretability developed to understand large language models to understand the concepts ESM uses to represent proteins. The model’s representation space has a compositional organization of features across scales, levels of complexity, and abstraction, that reflects and mirrors the understanding of protein biology developed through a century of empirical science. This understanding emerges without prior knowledge, just from language modeling of protein sequences. Language models are becoming a powerful substrate to understand and program biology. The design of protein interactions is one of the most fundamental problems in biophysics, and has critical implications for the discovery of new medicines. A simple gradient based search with the model was able to discover high-affinity protein binders. I'm excited by the potential this has to accelerate basic science and the understanding of proteins. And especially for the new avenues it opens up for therapeutic design and medicine.

Another banger from @ChoYehlin !

Very excited to get this new work by Shin Ngiow up on #bioRxiv. We may be blocking PD-1 too long causing detrimental effects on Tpex cells. A drug holiday approach may be beneficial. Also some cool new Tpex biology here. #immunopharmacology biorxiv.org/content/10.64898…