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Introducing Tahoe-x1 (Tx1) by Tahoe. A 3-billion-parameter, single-cell foundation model that learns unified representations of genes, cells, and drugs, achieving state-of-the-art performance across cancer-relevant cell biology benchmarks, open-sourced on Hugging Face. 🧵

171,850 просмотров • 9 месяцев назад •via X (Twitter)

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How does an embryo reliably "compute" its form - "cell by cell" - using only local interactions and mechanics, yet produce a precise global body plan? I’m excited to share our Nature Methods paper "MultiCell: geometric learning in multicellular development", presenting #AIxBiology research led by Haiqian Yang and the result of a great collaboration with Ming Guo, George Roy, Tomer Stern, Anh Nguyen and Dapeng Bi. A long-standing challenge in developmental biology is to predict how thousands of cells collectively self-organize as tissues fold, divide, and rearrange. In MultiCell, we represent a developing embryo as a dual graph that unifies two complementary views of tissue mechanics with single-cell resolution: cells as moving points (granular) and cells as a connected foam (junction network). This lets the model learn dynamics from both geometry and cell–cell connectivity. On whole-embryo 4D light-sheet movies of Drosophila gastrulation (~5,000 cells), our model predicts key cell behaviors and the timing of events, including junction loss, rearrangements, and divisions with high accuracy, at single-cell resolution. Beyond prediction, the same representation supports robust time alignment across embryos and offers interpretable activation maps that highlight the morphogenetic "drivers" of development. The broader goal is a foundation for cell-by-cell forecasting in more complex tissues, and eventually for detecting subtle dynamical signatures of disease. Kudos to the team for this inspiring collaboration with brilliant researchers to push the boundary of AI for biology! Citation: Yang, H., Roy, G., Nguyen, A.Q., Buehler, M.J., et al. MultiCell: geometric learning in multicellular development. Nature Methods (2025), DOI: 10.1038/s41592-025-02983-x Code/data links are in the manuscript.

Markus J. Buehler

387,977 просмотров • 7 месяцев назад

🔬 Exciting News! Our manuscript, "scGPT: toward building a foundation model for single-cell multi-omics using generative AI" is now finally published in Nature Methods (Nature Methods) 🎉 !!! (Re-)Introducing scGPT: A transformative foundation model engineered for single-cell omics analysis. Developed through the analysis of over 33 million human cells, scGPT sets a new benchmark for application versatility, offering both fine-tuning and zero-shot capabilities. Since its preprint in May 2023, scGPT has significantly impacted the field, evidenced by 13K+ installations, 600+ GitHub stars 🌟, and 40+ citations before its official publication! scGPT has been validated by numerous benchmark studies as a leading foundation model in single-cell analysis. Its pre-trained embeddings extend its utility beyond single-cell studies, enhancing a variety of downstream tasks including protein enrichment and genetic perturbation predictions. Some key updates lately: ---Expanded zero-shot applications for efficient reference mapping and integration, now with CellXGene census integration. ---Advanced perturbation analysis capabilities, including genome-scale perturb-seq data analysis and bulk sequencing data generalization. ---Upgraded scGPT package, offering versatile model loading compatible with PyTorch and flash-attn, for both GPU and CPU. ---Cloud-based scGPT applications for reference mapping, cell annotation, and gene regulatory network inference are available on ---Integration with Hugging Face for easier model training. Limitations: scGPT is an early foray into foundation models for single-cell omics, facing challenges like limited zero-shot learning in some tasks, pretraining constraints, data quality issues, and evaluation limitations. See our Supplementary Notes for details. 🚀 Future Work? Short-Term Goals: 1. Releasing a Mouse Model for broader analysis. 2. Developing a comprehensive evaluation suite for foundation models in single-cell analysis. 3. Creating a foundation model for single-cell spatial omics. 4. Enhancing zero-shot capacity by integrating scGPT with RAG (e.g., knowledge graphs). Long-Term Goals: 1. Expanding scGPT for comprehensive single-cell multi-omics analysis. 2. Developing an in-silico perturbation model for predicting genetic perturbation effects. 3. Merging scGPT with multi-modal genomic sequence models for a deeper understanding of cell biology. 📚 Access the paper on Nature Methods: 🔬Preprint in Bioarixv: 💻 All our codes/data/weights are open source: Wholehearted congratulations to all the authors, especially the two co-first authors, Haotian (Haotian Cui ) and Chloe (ChloeXWang), who are really the emerging superstars in AI and biology! Vector Institute Peter Munk Cardiac Centre AI U of T Department of Computer Science Department of Laboratory Medicine & Pathobiology University Health Network University of Toronto #scGPT #GenerativeAI #AI4Science #Combio #opensource

Bo Wang

199,708 просмотров • 2 лет назад

🚨Here's what a lot of people misunderstand about cancer treatment, says drpaulmarik: "Cancer is not homogeneous. The somatic mutation theory—which is the current theory in which treatment is based—posits that you have a mutation in a single cell, and that gives rise to a whole population of cells that look the same and have the same mutation. But the Cancer Genome Atlas has shown that that theory is completely wrong. The cancer cells are very heterogeneous, so they're made up of very different populations of cells with different mutations, and one of the populations is the cancer stem cell. It's a sub-population of the cancer. These are generally slow-growing, but they're distinct in that they have the ability to divide indefinitely and grow indefinitely, and can change their characteristics. Basically, if you get rid of the fast-dividing cells, which is the cancer, you're left with the stem cells, which then become the roots, which grow back to form the tumor" sometimes years later. Conventional chemotherapy gets rid of the fast-dividing regular cancer cells but *NOT* the stem cells. So the key question is: how do you get rid of the stem cells? “There are a number of repurposed drugs that do it, and this has been well-established in scientific medical literature. One of the most effective treatments to knock out the stem cell is the famous horse deworming medicine," says drpaulmarik. Yes, ivermectin. Independent Medical Alliance

Jan Jekielek

96,002 просмотров • 1 год назад

Single-cell technologies now let us profile entire transcriptomes in individual cells. But how do we make sense of this complexity in a biologically meaningful way? Many methods summarise cells into a single embedding, but this often comes at the cost of interpretability, especially when multiple gene programs are active at once. We developed Tripso, a self-supervised transformer model that represents cells through multiple gene program-specific embeddings, while also uncovering new programs directly from the data. Instead of collapsing biology into a single vector, Tripso decomposes cell state into multiple representations, each reflecting a different gene program. We explored this across multiple systems. In human hematopoiesis, spanning development to aging, Tripso identified distinct age-associated program activity, including stronger JAK-STAT signalling in early life and dynamic IKZF1-related changes during B cell maturation. By comparing in vitro culture conditions with in vivo hematopoietic stem cell states, Tripso suggested that targeting the SEC61 translocon could enhance stem cell maintenance ex vivo, a prediction that we subsequently validated experimentally. In parallel, we identified a previously uncharacterised tissue-resident memory T-cell program associated with atopic dermatitis and mapped it to distinct spatial immune niches Together, these results show how modelling cells through gene programs can lead to interpretable and experimentally testable insights. More broadly, this work points toward a more interpretable and biologically grounded models of cell state. As single-cell datasets continue to grow, we hope approaches like Tripso will help bridge the gap between data-driven representations and biological insight. This work wouldn’t have been possible without the contributions of an amazing team. Thank you to co-first authors Marie, Tomoya Isobe, Amirhosein Vahidi, Carlo Leonardi, and everyone from roser's Lab, Haniffa Lab, Nicola Wilson and Bertie Gottgens's Lab, bringing together expertise across Cambridge Stem Cell Institute, Open Targets, Wellcome Sanger Institute and Cambridge University. Marie is one of the very best PhD students I have ever supervised. She is truly a force of nature, exceptionally resourceful, deeply innovative, and one of the most impressive scientists I have worked with. I am immensely proud of her and all that she has accomplished. As she begins her internship at Genentech , I have no doubt she will do amazing work there and continue to make her mark. paper: code:

Mo Lotfollahi

22,440 просмотров • 3 месяцев назад

Big Pharma spends billions on cancer drugs that may weaken our body’s natural defenses, but Dr. Soon-Shiong reveals a $10 test could hold the key to longevity—keeping your natural killer cells above 1,000 to fight cancer, infections, and more! Dr. Patrick Soon-Shiong unveils a groundbreaking perspective on human health, describing not an invention but an evolution in understanding the body’s defense system. For 450-460 million years, a single cell has enabled mammalian survival against infection, cancer, and trauma: the natural killer (NK) cell. This cell, he argues, forms the foundation of a unifying theory of longevity—a bold claim grounded in decades of research. Soon-Shiong critiques the conventional “whack-a-mole” approach to cancer treatment. He spent years chasing genomic mutations, only to realize that targeting one mutation often spawns another. Big Pharma, he notes, invests billions in mutation-specific drugs, chemotherapy, radiation, and checkpoint inhibitors—treatments that inadvertently suppress the very NK cells critical to life. Even therapies like EPOGEN and NEUPOGEN, designed to support chemotherapy, enable more aggressive treatments that further deplete these vital cells. The solution, he proposes, is startlingly simple: monitor the absolute lymphocyte count (ALC) via a $10 CBC test. NK cells, a subset of lymphocytes, must remain above 1,000 per microliter to maintain robust defense against cancer, infections, and sepsis. Radiation, however, often crashes this count, sometimes for over a year, leaving patients vulnerable to metastasis. A recent study highlights this “badscopal” effect, where radiation, while shrinking one tumor, may increase metastatic spread by wiping out NK cells—contrasting the long-touted “abscopal” benefit of systemic tumor reduction. Aging, viral infections, sepsis, and cancer all correlate with declining NK cell levels. Yet, Soon-Shiong emphasizes, these cells possess an innate ability to recognize and destroy transforming cells before they become cancerous. This insight shifts the paradigm from attacking disease to bolstering the body’s natural defenses. The challenge now is to rethink medical approaches. “Follow the science,” Soon-Shiong urges, advocating for data-driven strategies over entrenched agendas. By preserving NK cell counts, we may unlock the secret to long, healthy lives. This isn’t just a theory—it’s a call to transform how we fight disease.

Camus

40,176 просмотров • 1 год назад

The Chemotherapy Paradox – A "Cure" That Preserves the Root of Cancer? You've been told chemotherapy is a cornerstone of cancer care. But what if the standard of care is fundamentally flawed, suppressing the very system designed to heal you while protecting the engine that drives the disease? In a stunning exposition, Dr. Paul Marik pulls back the curtain on oncology's biggest dilemma. Here's the shocking truth: - Chemotherapy annihilates your immune army. It wipes out your natural killer cells and T-cells—the very soldiers your body needs to fight cancer. You are immune-suppressed, allowing the tumor a clearer path to proliferate. - Chemotherapy preserves the cancer stem cell. This is the root of the tumor. While chemo kills rapidly dividing cells, it often leaves the stem cell—the queen bee—untouched. From this root, the cancer indefinitely divides, mutates, and regrows. - Some chemo drugs may even STIMULATE the stem cell. That's right. The very treatment intended to kill cancer can, in some cases, fuel its source. "So you can't cure the patient unless you get rid of the cancer stem cell," states Dr. Marik. "Interestingly, chemotherapy doesn't kill the stem cell." This explains why "remission" is not a "cure." The cancer can return 7, 8, or 10 years later because the root was never addressed. You are in remission, not cured. The conclusion? The high-dose, "burn-and-cut" approach of traditional oncology is not holistic. It weakens the host and empowers the enemy's most resilient forces. Dr. Marik confirms: The efficacy depends on the tumor type. Cancers with a low percentage of stem cells can see long-term remission. But for many, it's a ticking time bomb. This isn't an opinion; it's a biological reality. It’s time for a paradigm shift. Share this to spark a crucial conversation. The future of oncology depends on it.

Camus

69,487 просмотров • 8 месяцев назад