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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...

387,652 просмотров • 5 месяцев назад •via X (Twitter)

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🔬 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

199,614 просмотров • 2 лет 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

22,373 просмотров • 2 месяцев назад

Excited to share our new work on building a multimodal atlas of human skin in health and inflammatory disease — a project I’m especially proud of, bringing together AI, high-throughput genomics, and clinical science to accelerate discovery. Over the past decade, single-cell genomics has transformed how we map cells in human tissues. But a major challenge remains: can we systematically decode how cells organize into functional niches in situ — including those invisible to standard histopathology? To address this, we integrated large-scale scRNA-seq, spatial transcriptomics, histopathology, and AI-driven modeling frameworks to build an in situ atlas of human skin across health and disease. Led by Lloyd Steele, an MD/PhD student working between Haniffa Lab and my lab at Wellcome Sanger Institute and Cambridge University . Another amazing collaboration with Muzz Haniffa, the mastermind behind the work as part of Human Cell Atlas. A key part of this study is that we didn’t build everything from scratch — we leveraged and combined AI methods that actually work! and showed how they can be used together to extract biological insight at scale. We used: • scArches to build and map into a reference scRNA-seq atlas of human skin: • NicheCompass to identify and characterize spatial niches: • MINT-Flow to extract microenvironment-induced cell states and gene programs: Together, these enabled an end-to-end workflow from atlas construction to spatial mapping, niche discovery, and cell state decoding. At scale, we integrated ~5 million cells and 100+ spatial sections, enabling a systematic view of tissue organization. Using this framework, we identified 26 niches in skin, including known histopathologic structures as well as hidden disease-associated niches not visible on H&E. Among the most striking findings were a resident memory T cell-rich sebaceous gland niche and a plasma cell-rich sweat gland niche, suggesting that appendageal structures act as active immunological microenvironments and may contribute to inflammatory memory and disease persistence. Importantly, this atlas is not just descriptive — it is usable. It can support mapping of new datasets, resolve finer cell types and niches, extract microenvironment-driven programs, and enable predictive analyses at scale. More broadly, this work shows what becomes possible when AI, spatial genomics, and atlas-scale data are integrated end-to-end: not just mapping tissues, but systematically decoding them. This was a massive collaboration, and I’m very grateful to the amazing scientists April Foster, Kenny Roberts, and Chloe Admane. Lloyd is an amazing scientist, and I’m especially excited for the community to see more of his work soon — stay tuned. The data and pre-trained models will be released soon. Preprint:

Mo Lotfollahi

11,723 просмотров • 2 месяцев назад

Gender Dysphoria is heavily encouraged by environmental factors, but I also believe it’s heavily influenced by aborted fetal tissue present in all vaccines. If anyone is skeptical of these ingredients being present in vaccines, I encourage you to watch the nine-hour deposition of Stanley Plotkin and dig deeper. Human fetal cell lines are used to culture vaccines. The CDC's Vaccine Excipient list includes WI-38, MRC-5, HEK293, and PERC.6. WI-38 is a diploid human cell culture line composed of fibroblasts derived from the lung tissue of an aborted female fetus. MRC-5 (Medical Research Council cell strain 5) is a diploid human cell culture line composed of fibroblasts derived from the lung tissue of a 14-week-old aborted male fetus. Human embryonic kidney cells 293, also often referred to as HEK 293, HEK-293, 293 cells, or less precisely as HEK cells, are a specific cell line originally derived from human embryonic kidney cells grown in a tissue culture. PERC.6 cell line was derived from human embryonic retinal cells taken from an elective abortion. The newest cell line created in 2015 for vaccines: WALVAX 2 is taken from the lung tissue of a 3-month gestation female who was ultimately selected from among 9 aborted babies. The scientists noted how they followed specific guidelines to mimic WI-38 and MRC-5 in selecting the aborted babies, ranging from 2-4 months gestation. They further noted how they induced labor using a “water bag” abortion to shorten the delivery time and prevent the death of the fetus to ensure live intact organs which were immediately sent to the labs for cell preparation. (Source:

Dr. Ben Tapper

51,242 просмотров • 1 год назад