Daily Papers

Understanding the biological mechanism of disease is critical for medicine, and in particular drug discovery. AI-powered analysis of genome-scale biological data hold great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models either do not improve or only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving the state-of-the-art. First, we scaled the pre-training dataset to 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the TEDDY family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on two downstream evaluation tasks -- identifying the underlying disease state of held-out donors not seen during training and distinguishing healthy cells from diseased ones for disease conditions and donors not seen during training. Scaling experiments showed that performance improved predictably with both data volume and parameter count. Our models showed substantial improvement over existing work on the first task and more muted improvements on the second.

While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.

Large language models excel at interpreting complex natural language instructions, enabling them to perform a wide range of tasks. In the life sciences, single-cell RNA sequencing (scRNA-seq) data serves as the "language of cellular biology", capturing intricate gene expression patterns at the single-cell level. However, interacting with this "language" through conventional tools is often inefficient and unintuitive, posing challenges for researchers. To address these limitations, we present InstructCell, a multi-modal AI copilot that leverages natural language as a medium for more direct and flexible single-cell analysis. We construct a comprehensive multi-modal instruction dataset that pairs text-based instructions with scRNA-seq profiles from diverse tissues and species. Building on this, we develop a multi-modal cell language architecture capable of simultaneously interpreting and processing both modalities. InstructCell empowers researchers to accomplish critical tasks-such as cell type annotation, conditional pseudo-cell generation, and drug sensitivity prediction-using straightforward natural language commands. Extensive evaluations demonstrate that InstructCell consistently meets or exceeds the performance of existing single-cell foundation models, while adapting to diverse experimental conditions. More importantly, InstructCell provides an accessible and intuitive tool for exploring complex single-cell data, lowering technical barriers and enabling deeper biological insights.

High-throughput screening techniques, such as microscopy imaging of cellular responses to genetic and chemical perturbations, play a crucial role in drug discovery and biomedical research. However, robust perturbation screening for de novo cell lines remains challenging due to the significant morphological and biological heterogeneity across cell lines. To address this, we propose a novel framework that integrates external biological knowledge into existing pretraining strategies to enhance microscopy image profiling models. Our approach explicitly disentangles perturbation-specific and cell line-specific representations using external biological information. Specifically, we construct a knowledge graph leveraging protein interaction data from STRING and Hetionet databases to guide models toward perturbation-specific features during pretraining. Additionally, we incorporate transcriptomic features from single-cell foundation models to capture cell line-specific representations. By learning these disentangled features, our method improves the generalization of imaging models to de novo cell lines. We evaluate our framework on the RxRx database through one-shot fine-tuning on an RxRx1 cell line and few-shot fine-tuning on cell lines from the RxRx19a dataset. Experimental results demonstrate that our method enhances microscopy image profiling for de novo cell lines, highlighting its effectiveness in real-world phenotype-based drug discovery applications.

The advent of single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) offers an innovative perspective for deciphering regulatory mechanisms by assembling a vast repository of single-cell chromatin accessibility data. While foundation models have achieved significant success in single-cell transcriptomics, there is currently no foundation model for scATAC-seq that supports zero-shot high-quality cell identification and comprehensive multi-omics analysis simultaneously. Key challenges lie in the high dimensionality and sparsity of scATAC-seq data, as well as the lack of a standardized schema for representing open chromatin regions (OCRs). Here, we present ChromFound, a foundation model tailored for scATAC-seq. ChromFound utilizes a hybrid architecture and genome-aware tokenization to effectively capture genome-wide long contexts and regulatory signals from dynamic chromatin landscapes. Pretrained on 1.97 million cells from 30 tissues and 6 disease conditions, ChromFound demonstrates broad applicability across 6 diverse tasks. Notably, it achieves robust zero-shot performance in generating universal cell representations and exhibits excellent transferability in cell type annotation and cross-omics prediction. By uncovering enhancer-gene links undetected by existing computational methods, ChromFound offers a promising framework for understanding disease risk variants in the noncoding genome.

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Foundation models for single-cell RNA sequencing (scRNA-seq) have shown promising capabilities in capturing gene expression patterns. However, current approaches face critical limitations: they ignore biological prior knowledge encoded in gene regulatory relationships and fail to leverage multi-omics signals that could provide complementary regulatory insights. In this paper, we propose GRNFormer, a new framework that systematically integrates multi-scale Gene Regulatory Networks (GRNs) inferred from multi-omics data into RNA foundation model training. Our framework introduces two key innovations. First, we introduce a pipeline for constructing hierarchical GRNs that capture regulatory relationships at both cell-type-specific and cell-specific resolutions. Second, we design a structure-aware integration framework that addresses the information asymmetry in GRNs through two technical advances: (1) A graph topological adapter using multi-head cross-attention to weight regulatory relationships dynamically, and (2) a novel edge perturbation strategy that perturb GRNs with biologically-informed co-expression links to augment graph neural network training. Comprehensive experiments have been conducted on three representative downstream tasks across multiple model architectures to demonstrate the effectiveness of GRNFormer. It achieves consistent improvements over state-of-the-art (SoTA) baselines: 3.6% increase in drug response prediction correlation, 9.6% improvement in single-cell drug classification AUC, and 1.1% average gain in gene perturbation prediction accuracy.

Large language models (LLMs) and emerging agentic frameworks are beginning to transform single-cell biology by enabling natural-language reasoning, generative annotation, and multimodal data integration. However, progress remains fragmented across data modalities, architectures, and evaluation standards. LLM4Cell presents the first unified survey of 58 foundation and agentic models developed for single-cell research, spanning RNA, ATAC, multi-omic, and spatial modalities. We categorize these methods into five families-foundation, text-bridge, spatial, multimodal, epigenomic, and agentic-and map them to eight key analytical tasks including annotation, trajectory and perturbation modeling, and drug-response prediction. Drawing on over 40 public datasets, we analyze benchmark suitability, data diversity, and ethical or scalability constraints, and evaluate models across 10 domain dimensions covering biological grounding, multi-omics alignment, fairness, privacy, and explainability. By linking datasets, models, and evaluation domains, LLM4Cell provides the first integrated view of language-driven single-cell intelligence and outlines open challenges in interpretability, standardization, and trustworthy model development.

In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.

Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose SToFM, a multi-scale Spatial Transcriptomics Foundation Model. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct SToCorpus-88M, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data through capturing and integrating multi-scale information.

Complex cell signaling systems -- governed by varying protein abundances and interactions -- generate diverse cell types across organs. These systems evolve under influences such as age, sex, diet, environmental exposures, and diseases, making them challenging to decode given the involvement of tens of thousands of genes and proteins. Recently, hundreds of millions of single-cell omics data have provided a robust foundation for understanding these signaling networks within various cell subpopulations and conditions. Inspired by the success of large foundation models (for example, large language models and large vision models) pre-trained on massive datasets, we introduce OmniCellTOSG, the first dataset of cell text-omic signaling graphs (TOSGs). Each TOSG represents the signaling network of an individual or meta-cell and is labeled with information such as organ, disease, sex, age, and cell subtype. OmniCellTOSG offers two key contributions. First, it introduces a novel graph model that integrates human-readable annotations -- such as biological functions, cellular locations, signaling pathways, related diseases, and drugs -- with quantitative gene and protein abundance data, enabling graph reasoning to decode cell signaling. This approach calls for new joint models combining large language models and graph neural networks. Second, the dataset is built from single-cell RNA sequencing data of approximately 120 million cells from diverse tissues and conditions (healthy and diseased) and is fully compatible with PyTorch. This facilitates the development of innovative cell signaling models that could transform research in life sciences, healthcare, and precision medicine. The OmniCellTOSG dataset is continuously expanding and will be updated regularly. The dataset and code are available at https://github.com/FuhaiLiAiLab/OmniCellTOSG.

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

Foundation models are reshaping computational pathology by enabling transfer learning, where models pre-trained on vast datasets can be adapted for downstream diagnostic, prognostic, and therapeutic response tasks. Despite these advances, foundation models are still limited in their ability to encode the entire gigapixel whole-slide images without additional training and often lack complementary multimodal data. Here, we introduce Threads, a slide-level foundation model capable of generating universal representations of whole-slide images of any size. Threads was pre-trained using a multimodal learning approach on a diverse cohort of 47,171 hematoxylin and eosin (H&E)-stained tissue sections, paired with corresponding genomic and transcriptomic profiles - the largest such paired dataset to be used for foundation model development to date. This unique training paradigm enables Threads to capture the tissue's underlying molecular composition, yielding powerful representations applicable to a wide array of downstream tasks. In extensive benchmarking across 54 oncology tasks, including clinical subtyping, grading, mutation prediction, immunohistochemistry status determination, treatment response prediction, and survival prediction, Threads outperformed all baselines while demonstrating remarkable generalizability and label efficiency. It is particularly well suited for predicting rare events, further emphasizing its clinical utility. We intend to make the model publicly available for the broader community.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Foundation models (FMs), i.e., models trained on a vast amount of typically unlabeled data, have become popular and available recently for the domain of histopathology. The key idea is to extract semantically rich vectors from any input patch, allowing for the use of simple subsequent classification networks potentially reducing the required amounts of labeled data, and increasing domain robustness. In this work, we investigate to which degree this also holds for mitotic figure classification. Utilizing two popular public mitotic figure datasets, we compared linear probing of five publicly available FMs against models trained on ImageNet and a simple ResNet50 end-to-end-trained baseline. We found that the end-to-end-trained baseline outperformed all FM-based classifiers, regardless of the amount of data provided. Additionally, we did not observe the FM-based classifiers to be more robust against domain shifts, rendering both of the above assumptions incorrect.

Foundation models (FMs), such as GPT-4 and AlphaFold, are reshaping the landscape of scientific research. Beyond accelerating tasks such as hypothesis generation, experimental design, and result interpretation, they prompt a more fundamental question: Are FMs merely enhancing existing scientific methodologies, or are they redefining the way science is conducted? In this paper, we argue that FMs are catalyzing a transition toward a new scientific paradigm. We introduce a three-stage framework to describe this evolution: (1) Meta-Scientific Integration, where FMs enhance workflows within traditional paradigms; (2) Hybrid Human-AI Co-Creation, where FMs become active collaborators in problem formulation, reasoning, and discovery; and (3) Autonomous Scientific Discovery, where FMs operate as independent agents capable of generating new scientific knowledge with minimal human intervention. Through this lens, we review current applications and emerging capabilities of FMs across existing scientific paradigms. We further identify risks and future directions for FM-enabled scientific discovery. This position paper aims to support the scientific community in understanding the transformative role of FMs and to foster reflection on the future of scientific discovery. Our project is available at https://github.com/usail-hkust/Awesome-Foundation-Models-for-Scientific-Discovery.

As Large Language Models (LLMs) rapidly evolve, their influence in science is becoming increasingly prominent. The emerging capabilities of LLMs in task generalization and free-form dialogue can significantly advance fields like chemistry and biology. However, the field of single-cell biology, which forms the foundational building blocks of living organisms, still faces several challenges. High knowledge barriers and limited scalability in current methods restrict the full exploitation of LLMs in mastering single-cell data, impeding direct accessibility and rapid iteration. To this end, we introduce ChatCell, which signifies a paradigm shift by facilitating single-cell analysis with natural language. Leveraging vocabulary adaptation and unified sequence generation, ChatCell has acquired profound expertise in single-cell biology and the capability to accommodate a diverse range of analysis tasks. Extensive experiments further demonstrate ChatCell's robust performance and potential to deepen single-cell insights, paving the way for more accessible and intuitive exploration in this pivotal field. Our project homepage is available at https://zjunlp.github.io/project/ChatCell.

Generative modeling of single-cell RNA-seq data has shown invaluable potential in community-driven tasks such as trajectory inference, batch effect removal and gene expression generation. However, most recent deep models generating synthetic single cells from noise operate on pre-processed continuous gene expression approximations, ignoring the inherently discrete and over-dispersed nature of single-cell data, which limits downstream applications and hinders the incorporation of robust noise models. Moreover, crucial aspects of deep-learning-based synthetic single-cell generation remain underexplored, such as controllable multi-modal and multi-label generation and its role in the performance enhancement of downstream tasks. This work presents Cell Flow for Generation (CFGen), a flow-based conditional generative model for multi-modal single-cell counts, which explicitly accounts for the discrete nature of the data. Our results suggest improved recovery of crucial biological data characteristics while accounting for novel generative tasks such as conditioning on multiple attributes and boosting rare cell type classification via data augmentation. By showcasing CFGen on a diverse set of biological datasets and settings, we provide evidence of its value to the fields of computational biology and deep generative models.

Transcriptomic foundation models (TFMs) have recently emerged as powerful tools for analyzing gene expression in cells and tissues, supporting key tasks such as cell-type annotation, batch correction, and perturbation prediction. However, the diversity of model implementations and training strategies across recent TFMs, though promising, makes it challenging to isolate the contribution of individual design choices or evaluate their potential synergies. This hinders the field's ability to converge on best practices and limits the reproducibility of insights across studies. We present BMFM-RNA, an open-source, modular software package that unifies diverse TFM pretraining and fine-tuning objectives within a single framework. Leveraging this capability, we introduce a novel training objective, whole cell expression decoder (WCED), which captures global expression patterns using an autoencoder-like CLS bottleneck representation. In this paper, we describe the framework, supported input representations, and training objectives. We evaluated four model checkpoints pretrained on CELLxGENE using combinations of masked language modeling (MLM), WCED and multitask learning. Using the benchmarking capabilities of BMFM-RNA, we show that WCED-based models achieve performance that matches or exceeds state-of-the-art approaches like scGPT across more than a dozen datasets in both zero-shot and fine-tuning tasks. BMFM-RNA, available as part of the biomed-multi-omics project ( https://github.com/BiomedSciAI/biomed-multi-omic ), offers a reproducible foundation for systematic benchmarking and community-driven exploration of optimal TFM training strategies, enabling the development of more effective tools to leverage the latest advances in AI for understanding cell biology.

In recent years, the advent of foundation models (FM) for digital pathology has relied heavily on scaling the pre-training datasets and the model size, yielding large and powerful models. While it resulted in improving the performance on diverse downstream tasks, it also introduced increased computational cost and inference time. In this work, we explore the distillation of a large foundation model into a smaller one, reducing the number of parameters by several orders of magnitude. Leveraging distillation techniques, our distilled model, H0-mini, achieves nearly comparable performance to large FMs at a significantly reduced inference cost. It is evaluated on several public benchmarks, achieving 3rd place on the HEST benchmark and 5th place on the EVA benchmark. Additionally, a robustness analysis conducted on the PLISM dataset demonstrates that our distilled model reaches excellent robustness to variations in staining and scanning conditions, significantly outperforming other state-of-the art models. This opens new perspectives to design lightweight and robust models for digital pathology, without compromising on performance.

Foundation Models (FMs) serve as a general class for the development of artificial intelligence systems, offering broad potential for generalization across a spectrum of downstream tasks. Despite extensive research into self-supervised learning as the cornerstone of FMs, several outstanding issues persist in Graph Foundation Models that rely on graph self-supervised learning, namely: 1) Homogenization. The extent of generalization capability on downstream tasks remains unclear. 2) Scalability. It is unknown how effectively these models can scale to large datasets. 3) Efficiency. The training time and memory usage of these models require evaluation. 4) Training Stop Criteria. Determining the optimal stopping strategy for pre-training across multiple tasks to maximize performance on downstream tasks. To address these questions, we have constructed a rigorous benchmark that thoroughly analyzes and studies the generalization and scalability of self-supervised Graph Neural Network (GNN) models. Regarding generalization, we have implemented and compared the performance of various self-supervised GNN models, trained to generate node representations, across tasks such as node classification, link prediction, and node clustering. For scalability, we have compared the performance of various models after training using full-batch and mini-batch strategies. Additionally, we have assessed the training efficiency of these models by conducting experiments to test their GPU memory usage and throughput. Through these experiments, we aim to provide insights to motivate future research. The code for this benchmark is publicly available at https://github.com/NYUSHCS/GraphFM.

Foundation models have revolutionized natural language processing and artificial intelligence, significantly enhancing how machines comprehend and generate human languages. Inspired by the success of these foundation models, researchers have developed foundation models for individual scientific domains, including small molecules, materials, proteins, DNA, and RNA. However, these models are typically trained in isolation, lacking the ability to integrate across different scientific domains. Recognizing that entities within these domains can all be represented as sequences, which together form the "language of nature", we introduce Nature Language Model (briefly, NatureLM), a sequence-based science foundation model designed for scientific discovery. Pre-trained with data from multiple scientific domains, NatureLM offers a unified, versatile model that enables various applications including: (i) generating and optimizing small molecules, proteins, RNA, and materials using text instructions; (ii) cross-domain generation/design, such as protein-to-molecule and protein-to-RNA generation; and (iii) achieving state-of-the-art performance in tasks like SMILES-to-IUPAC translation and retrosynthesis on USPTO-50k. NatureLM offers a promising generalist approach for various scientific tasks, including drug discovery (hit generation/optimization, ADMET optimization, synthesis), novel material design, and the development of therapeutic proteins or nucleotides. We have developed NatureLM models in different sizes (1 billion, 8 billion, and 46.7 billion parameters) and observed a clear improvement in performance as the model size increases.

Foundation models have revolutionized natural language processing through a ``train once, deploy anywhere'' paradigm, where a single pre-trained model adapts to countless downstream tasks without retraining. Access to a Physics Foundation Model (PFM) would be transformative -- democratizing access to high-fidelity simulations, accelerating scientific discovery, and eliminating the need for specialized solver development. Yet current physics-aware machine learning approaches remain fundamentally limited to single, narrow domains and require retraining for each new system. We present the General Physics Transformer (GPhyT), trained on 1.8 TB of diverse simulation data, that demonstrates foundation model capabilities are achievable for physics. Our key insight is that transformers can learn to infer governing dynamics from context, enabling a single model to simulate fluid-solid interactions, shock waves, thermal convection, and multi-phase dynamics without being told the underlying equations. GPhyT achieves three critical breakthroughs: (1) superior performance across multiple physics domains, outperforming specialized architectures by up to 29x, (2) zero-shot generalization to entirely unseen physical systems through in-context learning, and (3) stable long-term predictions through 50-timestep rollouts. By establishing that a single model can learn generalizable physical principles from data alone, this work opens the path toward a universal PFM that could transform computational science and engineering.

Cytology is essential for cancer diagnostics and screening due to its minimally invasive nature. However, the development of robust deep learning models for digital cytology is challenging due to the heterogeneity in staining and preparation methods of samples, differences across organs, and the limited availability of large, diverse, annotated datasets. Developing a task-specific model for every cytology application is impractical and non-cytology-specific foundation models struggle to generalize to tasks in this domain where the emphasis is on cell morphology. To address these challenges, we introduce CytoFM, the first cytology self-supervised foundation model. Using iBOT, a self-supervised Vision Transformer (ViT) training framework incorporating masked image modeling and self-distillation, we pretrain CytoFM on a diverse collection of cytology datasets to learn robust, transferable representations. We evaluate CytoFM on multiple downstream cytology tasks, including breast cancer classification and cell type identification, using an attention-based multiple instance learning framework. Our results demonstrate that CytoFM performs better on two out of three downstream tasks than existing foundation models pretrained on histopathology (UNI) or natural images (iBOT-Imagenet). Visualizations of learned representations demonstrate our model is able to attend to cytologically relevant features. Despite a small pre-training dataset, CytoFM's promising results highlight the ability of task-agnostic pre-training approaches to learn robust and generalizable features from cytology data.

Computational pathology, which involves analyzing whole slide images for automated cancer diagnosis, relies on multiple instance learning, where performance depends heavily on the feature extractor and aggregator. Recent Pathology Foundation Models (PFMs), pretrained on large-scale histopathology data, have significantly enhanced both the extractor and aggregator, but they lack a systematic analysis framework. In this survey, we present a hierarchical taxonomy organizing PFMs through a top-down philosophy applicable to foundation model analysis in any domain: model scope, model pretraining, and model design. Additionally, we systematically categorize PFM evaluation tasks into slide-level, patch-level, multimodal, and biological tasks, providing comprehensive benchmarking criteria. Our analysis identifies critical challenges in both PFM development (pathology-specific methodology, end-to-end pretraining, data-model scalability) and utilization (effective adaptation, model maintenance), paving the way for future directions in this promising field. Resources referenced in this survey are available at https://github.com/BearCleverProud/AwesomeWSI.

Task-specific deep learning models in histopathology offer promising opportunities for improving diagnosis, clinical research, and precision medicine. However, development of such models is often limited by availability of high-quality data. Foundation models in histopathology that learn general representations across a wide range of tissue types, diagnoses, and magnifications offer the potential to reduce the data, compute, and technical expertise necessary to develop task-specific deep learning models with the required level of model performance. In this work, we describe the development and evaluation of foundation models for histopathology via self-supervised learning (SSL). We first establish a diverse set of benchmark tasks involving 17 unique tissue types and 12 unique cancer types and spanning different optimal magnifications and task types. Next, we use this benchmark to explore and evaluate histopathology-specific SSL methods followed by further evaluation on held out patch-level and weakly supervised tasks. We found that standard SSL methods thoughtfully applied to histopathology images are performant across our benchmark tasks and that domain-specific methodological improvements can further increase performance. Our findings reinforce the value of using domain-specific SSL methods in pathology, and establish a set of high quality foundation models to enable further research across diverse applications.

The advent of single-cell technology has significantly improved our understanding of cellular states and subpopulations in various tissues under normal and diseased conditions by employing data-driven approaches such as clustering and trajectory inference. However, these methods consider cells as independent data points of population distributions. With spatial transcriptomics, we can represent cellular organization, along with dynamic cell-cell interactions that lead to changes in cell state. Still, key computational advances are necessary to enable the data-driven learning of such complex interactive cellular dynamics. While agent-based modeling (ABM) provides a powerful framework, traditional approaches rely on handcrafted rules derived from domain knowledge rather than data-driven approaches. To address this, we introduce Spatio Temporal Agent-Based Graph Evolution Dynamics(STAGED) integrating ABM with deep learning to model intercellular communication, and its effect on the intracellular gene regulatory network. Using graph ODE networks (GDEs) with shared weights per cell type, our approach represents genes as vertices and interactions as directed edges, dynamically learning their strengths through a designed attention mechanism. Trained to match continuous trajectories of simulated as well as inferred trajectories from spatial transcriptomics data, the model captures both intercellular and intracellular interactions, enabling a more adaptive and accurate representation of cellular dynamics.

Following its success for vision and text, the "foundation model" (FM) paradigm -- pretraining large models on massive data, then fine-tuning on target tasks -- has rapidly expanded to domains in the sciences, engineering, healthcare, and beyond. Has this achieved what the original FMs accomplished, i.e. the supplanting of traditional supervised learning in their domains? To answer we look at three modalities -- genomics, satellite imaging, and time series -- with multiple recent FMs and compare them to a standard supervised learning workflow: model development, hyperparameter tuning, and training, all using only data from the target task. Across these three specialized domains, we find that it is consistently possible to train simple supervised models -- no more complicated than a lightly modified wide ResNet or UNet -- that match or even outperform the latest foundation models. Our work demonstrates that the benefits of large-scale pretraining have yet to be realized in many specialized areas, reinforces the need to compare new FMs to strong, well-tuned baselines, and introduces two new, easy-to-use, open-source, and automated workflows for doing so.

Vision foundation models (FMs) are accelerating the development of digital pathology algorithms and transforming biomedical research. These models learn, in a self-supervised manner, to represent histological features in highly heterogeneous tiles extracted from whole-slide images (WSIs) of real-world patient samples. The performance of these FMs is significantly influenced by the size, diversity, and balance of the pre-training data. However, data selection has been primarily guided by expert knowledge at the WSI level, focusing on factors such as disease classification and tissue types, while largely overlooking the granular details available at the tile level. In this paper, we investigate the potential of unsupervised automatic data curation at the tile-level, taking into account 350 million tiles. Specifically, we apply hierarchical clustering trees to pre-extracted tile embeddings, allowing us to sample balanced datasets uniformly across the embedding space of the pretrained FM. We further identify these datasets are subject to a trade-off between size and balance, potentially compromising the quality of representations learned by FMs, and propose tailored batch sampling strategies to mitigate this effect. We demonstrate the effectiveness of our method through improved performance on a diverse range of clinically relevant downstream tasks.

Single-cell RNA sequencing (scRNA-seq) data analysis is crucial for biological research, as it enables the precise characterization of cellular heterogeneity. However, manual manipulation of various tools to achieve desired outcomes can be labor-intensive for researchers. To address this, we introduce CellAgent (http://cell.agent4science.cn/), an LLM-driven multi-agent framework, specifically designed for the automatic processing and execution of scRNA-seq data analysis tasks, providing high-quality results with no human intervention. Firstly, to adapt general LLMs to the biological field, CellAgent constructs LLM-driven biological expert roles - planner, executor, and evaluator - each with specific responsibilities. Then, CellAgent introduces a hierarchical decision-making mechanism to coordinate these biological experts, effectively driving the planning and step-by-step execution of complex data analysis tasks. Furthermore, we propose a self-iterative optimization mechanism, enabling CellAgent to autonomously evaluate and optimize solutions, thereby guaranteeing output quality. We evaluate CellAgent on a comprehensive benchmark dataset encompassing dozens of tissues and hundreds of distinct cell types. Evaluation results consistently show that CellAgent effectively identifies the most suitable tools and hyperparameters for single-cell analysis tasks, achieving optimal performance. This automated framework dramatically reduces the workload for science data analyses, bringing us into the "Agent for Science" era.

Deep learning foundation models are revolutionizing many facets of science by leveraging vast amounts of data to learn general-purpose representations that can be adapted to tackle diverse downstream tasks. Foundation models hold the promise to also transform our ability to model our planet and its subsystems by exploiting the vast expanse of Earth system data. Here we introduce Aurora, a large-scale foundation model of the atmosphere trained on over a million hours of diverse weather and climate data. Aurora leverages the strengths of the foundation modelling approach to produce operational forecasts for a wide variety of atmospheric prediction problems, including those with limited training data, heterogeneous variables, and extreme events. In under a minute, Aurora produces 5-day global air pollution predictions and 10-day high-resolution weather forecasts that outperform state-of-the-art classical simulation tools and the best specialized deep learning models. Taken together, these results indicate that foundation models can transform environmental forecasting.

While computer science has seen remarkable advancements in foundation models, which remain underexplored in geoscience. Addressing this gap, we introduce a workflow to develop geophysical foundation models, including data preparation, model pre-training, and adaption to downstream tasks. From 192 globally collected 3-D seismic volumes, we create a carefully curated dataset of 2,286,422 2-D seismic images. Fully using these unlabeled images, we employ the self-supervised learning to pre-train a Transformer-based Seismic Foundation Model (SFM) for producing all-purpose seismic features that work across various tasks and surveys. Through experiments on seismic facies classification, geobody identification, interpolation, denoising, and inversion, our pre-trained model demonstrates versatility, generalization, scalability, and superior performance over baseline models. Conclusively, we provide a foundation model and vast dataset to advance AI in geophysics, addressing challenges (poor generalization, lacking labels, and repetitive training for task-specified models) of applying AI in geophysics and paving the way for future innovations in geoscience.

Foundation models are a strong trend in deep learning and computer vision. These models serve as a base for applications as they require minor or no further fine-tuning by developers to integrate into their applications. Foundation models for zero-shot object segmentation such as Segment Anything (SAM) output segmentation masks from images without any further object information. When they are followed in a pipeline by an object identification model, they can perform object detection without training. Here, we focus on training such an object identification model. A crucial practical aspect for an object identification model is to be flexible in input size. As object identification is an image retrieval problem, a suitable method should handle multi-query multi-gallery situations without constraining the number of input images (e.g. by having fixed-size aggregation layers). The key solution to train such a model is the centroid triplet loss (CTL), which aggregates image features to their centroids. CTL yields high accuracy, avoids misleading training signals and keeps the model input size flexible. In our experiments, we establish a new state of the art on the ArmBench object identification task, which shows general applicability of our model. We furthermore demonstrate an integrated unseen object detection pipeline on the challenging HOPE dataset, which requires fine-grained detection. There, our pipeline matches and surpasses related methods which have been trained on dataset-specific data.

Learning the underlying dynamics of single cells from snapshot data has gained increasing attention in scientific and machine learning research. The destructive measurement technique and cell proliferation/death result in unpaired and unbalanced data between snapshots, making the learning of the underlying dynamics challenging. In this paper, we propose joint Velocity-Growth Flow Matching (VGFM), a novel paradigm that jointly learns state transition and mass growth of single-cell populations via flow matching. VGFM builds an ideal single-cell dynamics containing velocity of state and growth of mass, driven by a presented two-period dynamic understanding of the static semi-relaxed optimal transport, a mathematical tool that seeks the coupling between unpaired and unbalanced data. To enable practical usage, we approximate the ideal dynamics using neural networks, forming our joint velocity and growth matching framework. A distribution fitting loss is also employed in VGFM to further improve the fitting performance for snapshot data. Extensive experimental results on both synthetic and real datasets demonstrate that VGFM can capture the underlying biological dynamics accounting for mass and state variations over time, outperforming existing approaches for single-cell dynamics modeling.

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects -- a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15.github.io/CellFlux/.

Numerous biological and physical processes can be modeled as systems of interacting entities evolving continuously over time, e.g. the dynamics of communicating cells or physical particles. Learning the dynamics of such systems is essential for predicting the temporal evolution of populations across novel samples and unseen environments. Flow-based models allow for learning these dynamics at the population level - they model the evolution of the entire distribution of samples. However, current flow-based models are limited to a single initial population and a set of predefined conditions which describe different dynamics. We argue that multiple processes in natural sciences have to be represented as vector fields on the Wasserstein manifold of probability densities. That is, the change of the population at any moment in time depends on the population itself due to the interactions between samples. In particular, this is crucial for personalized medicine where the development of diseases and their respective treatment response depends on the microenvironment of cells specific to each patient. We propose Meta Flow Matching (MFM), a practical approach to integrating along these vector fields on the Wasserstein manifold by amortizing the flow model over the initial populations. Namely, we embed the population of samples using a Graph Neural Network (GNN) and use these embeddings to train a Flow Matching model. This gives MFM the ability to generalize over the initial distributions unlike previously proposed methods. We demonstrate the ability of MFM to improve prediction of individual treatment responses on a large scale multi-patient single-cell drug screen dataset.

Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.

Deep learning-based methods have been widely researched in the areas of language and vision, demonstrating their capacity to understand long sequences of data and their usefulness in numerous helio-physics applications. Foundation models (FMs), which are pre-trained on a large-scale datasets, form the basis for a variety of downstream tasks. These models, especially those based on transformers in vision and language, show exceptional potential for adapting to a wide range of downstream applications. In this paper, we provide our perspective on the criteria for designing an FM for heliophysics and associated challenges and applications using the Solar Dynamics Observatory (SDO) dataset. We believe that this is the first study to design an FM in the domain of heliophysics.

AI is undergoing a paradigm shift with the rise of models (e.g., BERT, DALL-E, GPT-3) that are trained on broad data at scale and are adaptable to a wide range of downstream tasks. We call these models foundation models to underscore their critically central yet incomplete character. This report provides a thorough account of the opportunities and risks of foundation models, ranging from their capabilities (e.g., language, vision, robotics, reasoning, human interaction) and technical principles(e.g., model architectures, training procedures, data, systems, security, evaluation, theory) to their applications (e.g., law, healthcare, education) and societal impact (e.g., inequity, misuse, economic and environmental impact, legal and ethical considerations). Though foundation models are based on standard deep learning and transfer learning, their scale results in new emergent capabilities,and their effectiveness across so many tasks incentivizes homogenization. Homogenization provides powerful leverage but demands caution, as the defects of the foundation model are inherited by all the adapted models downstream. Despite the impending widespread deployment of foundation models, we currently lack a clear understanding of how they work, when they fail, and what they are even capable of due to their emergent properties. To tackle these questions, we believe much of the critical research on foundation models will require deep interdisciplinary collaboration commensurate with their fundamentally sociotechnical nature.

Foundation models (FMs) have shown transformative potential in radiology by performing diverse, complex tasks across imaging modalities. Here, we developed CT-FM, a large-scale 3D image-based pre-trained model designed explicitly for various radiological tasks. CT-FM was pre-trained using 148,000 computed tomography (CT) scans from the Imaging Data Commons through label-agnostic contrastive learning. We evaluated CT-FM across four categories of tasks, namely, whole-body and tumor segmentation, head CT triage, medical image retrieval, and semantic understanding, showing superior performance against state-of-the-art models. Beyond quantitative success, CT-FM demonstrated the ability to cluster regions anatomically and identify similar anatomical and structural concepts across scans. Furthermore, it remained robust across test-retest settings and indicated reasonable salient regions attached to its embeddings. This study demonstrates the value of large-scale medical imaging foundation models and by open-sourcing the model weights, code, and data, aims to support more adaptable, reliable, and interpretable AI solutions in radiology.

Foundation models (FMs) are able to leverage large volumes of unlabeled data to demonstrate superior performance across a wide range of tasks. However, FMs developed for biomedical domains have largely remained unimodal, i.e., independently trained and used for tasks on protein sequences alone, small molecule structures alone, or clinical data alone. To overcome this limitation of biomedical FMs, we present BioBridge, a novel parameter-efficient learning framework, to bridge independently trained unimodal FMs to establish multimodal behavior. BioBridge achieves it by utilizing Knowledge Graphs (KG) to learn transformations between one unimodal FM and another without fine-tuning any underlying unimodal FMs. Our empirical results demonstrate that BioBridge can beat the best baseline KG embedding methods (on average by around 76.3%) in cross-modal retrieval tasks. We also identify BioBridge demonstrates out-of-domain generalization ability by extrapolating to unseen modalities or relations. Additionally, we also show that BioBridge presents itself as a general purpose retriever that can aid biomedical multimodal question answering as well as enhance the guided generation of novel drugs.

Foundation models, or large atomistic models (LAMs), aim to universally represent the ground-state potential energy surface (PES) of atomistic systems as defined by density functional theory (DFT). The scaling law is pivotal in the development of large models, suggesting that their generalizability in downstream tasks consistently improves with increased model size, expanded training datasets, and larger computational budgets. In this study, we present DPA3, a multi-layer graph neural network founded on line graph series (LiGS), designed explicitly for the era of LAMs. We demonstrate that the generalization error of the DPA3 model adheres to the scaling law. The scalability in the number of model parameters is attained by stacking additional layers within DPA3. Additionally, the model employs a dataset encoding mechanism that decouples the scaling of training data size from the model size within its multi-task training framework. When trained as problem-oriented potential energy models, the DPA3 model exhibits superior accuracy in the majority of benchmark cases, encompassing systems with diverse features, including molecules, bulk materials, surface and cluster catalysts, two-dimensional materials, and battery materials. When trained as a LAM on the OpenLAM-v1 dataset, the DPA-3.1-3M model exhibits state-of-the-art performance in the LAMBench benchmark suite for LAMs, demonstrating lowest overall zero-shot generalization error across 17 downstream tasks from a broad spectrum of research domains. This performance suggests superior accuracy as an out-of-the-box potential model, requiring minimal fine-tuning data for downstream scientific applications.

In recent years, there has been a proliferation of spatiotemporal foundation models in different scientific disciplines. While promising, these models are often domain-specific and are only assessed within the particular applications for which they are designed. Given that many tasks can be represented as video modeling problems, video foundation models (ViFMs) hold considerable promise as general-purpose domain-agnostic approaches. However, it is not known whether the knowledge acquired on large-scale but potentially out-of-domain data can be effectively transferred across diverse scientific disciplines, and if a single, pretrained ViFM can be competitive with domain-specific baselines. To address this, we introduce SciVid, a comprehensive benchmark comprising five *Sci*entific *Vid*eo tasks, across medical computer vision, animal behavior, and weather forecasting. We adapt six leading ViFMs to SciVid using simple trainable readout modules, establishing strong baselines and demonstrating the potential for effective transfer learning. Specifically, we show that state-of-the-art results can be obtained in several applications by leveraging the general-purpose representations from ViFM backbones. Furthermore, our results reveal the limitations of existing ViFMs, and highlight opportunities for the development of generalizable models for high-impact scientific applications. We release our code at https://github.com/google-deepmind/scivid to facilitate further research in the development of ViFMs.

Foundation Models (FMs) are models trained on large corpora of data that, at very large scale, can generalize to new tasks without any task-specific finetuning. As these models continue to grow in size, innovations continue to push the boundaries of what these models can do on language and image tasks. This paper aims to understand an underexplored area of FMs: classical data tasks like cleaning and integration. As a proof-of-concept, we cast five data cleaning and integration tasks as prompting tasks and evaluate the performance of FMs on these tasks. We find that large FMs generalize and achieve SoTA performance on data cleaning and integration tasks, even though they are not trained for these data tasks. We identify specific research challenges and opportunities that these models present, including challenges with private and domain specific data, and opportunities to make data management systems more accessible to non-experts. We make our code and experiments publicly available at: https://github.com/HazyResearch/fm_data_tasks.

Foundation vision or vision-language models are trained on large unlabeled or noisy data and learn robust representations that can achieve impressive zero- or few-shot performance on diverse tasks. Given these properties, they are a natural fit for active learning (AL), which aims to maximize labeling efficiency. However, the full potential of foundation models has not been explored in the context of AL, specifically in the low-budget regime. In this work, we evaluate how foundation models influence three critical components of effective AL, namely, 1) initial labeled pool selection, 2) ensuring diverse sampling, and 3) the trade-off between representative and uncertainty sampling. We systematically study how the robust representations of foundation models (DINOv2, OpenCLIP) challenge existing findings in active learning. Our observations inform the principled construction of a new simple and elegant AL strategy that balances uncertainty estimated via dropout with sample diversity. We extensively test our strategy on many challenging image classification benchmarks, including natural images as well as out-of-domain biomedical images that are relatively understudied in the AL literature. We also provide a highly performant and efficient implementation of modern AL strategies (including our method) at https://github.com/sanketx/AL-foundation-models.

Artificial Intelligence (AI) has the potential to revolutionize diagnosis and segmentation in medical imaging. However, development and clinical implementation face multiple challenges including limited data availability, lack of generalizability, and the necessity to incorporate multi-modal data effectively. A foundation model, which is a large-scale pre-trained AI model, offers a versatile base that can be adapted to a variety of specific tasks and contexts. Here, we present a novel foundation model, VISION-MAE, specifically designed for medical imaging. Specifically, VISION-MAE is trained on a dataset of 2.5 million unlabeled images from various modalities (CT, MR, PET, X-rays, and ultrasound), using self-supervised learning techniques. It is then adapted to classification and segmentation tasks using explicit labels. VISION-MAE has high label efficiency, outperforming several benchmark models in both in-domain and out-of-domain applications, and achieves high performance even with reduced availability of labeled data. This model represents a significant advancement in medical imaging AI, offering a generalizable and robust solution for improving segmentation and classification tasks while reducing the data annotation workload.

Recent advances in sequencing technologies have enabled researchers to explore cellular heterogeneity at single-cell resolution. Meanwhile, interpretability has gained prominence parallel to the rapid increase in the complexity and performance of deep learning models. In recent years, topic models have been widely used for interpretable single-cell embedding learning and clustering analysis, which we refer to as single-cell embedded topic models. However, previous studies evaluated the interpretability of the models mainly through qualitative analysis, and these single-cell embedded topic models suffer from the potential problem of interpretation collapse. Furthermore, their neglect of external biological knowledge constrains analytical performance. Here, we present scE2TM, an external knowledge-guided single-cell embedded topic model that provides a high-quality cell embedding and strong interpretation, contributing to comprehensive scRNA-seq data analysis. Our comprehensive evaluation across 20 scRNA-seq datasets demonstrates that scE2TM achieves significant clustering performance gains compared to 7 state-of-the-art methods. In addition, we propose a new interpretability evaluation benchmark that introduces 10 metrics to quantitatively assess the interpretability of single-cell embedded topic models. The results show that the interpretation provided by scE2TM performs encouragingly in terms of diversity and consistency with the underlying biological signals, contributing to a better revealing of the underlying biological mechanisms.

Foundation models pretrained on large-scale datasets are revolutionizing the field of computational pathology (CPath). The generalization ability of foundation models is crucial for the success in various downstream clinical tasks. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability and overall performance unclear. To address this gap, we established a most comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 39 specific tasks. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self-distillation to enable image representation learning via local-global alignment. Based on this framework, a Generalizable Pathology Foundation Model (GPFM) is pretrained on a large-scale dataset consisting of 190 million images from around 86,000 public H&E whole slides across 34 major tissue types. Evaluated on the established benchmark, GPFM achieves an impressive average rank of 1.36, with 29 tasks ranked 1st, while the the second-best model, UNI, attains an average rank of 2.96, with only 4 tasks ranked 1st. The superior generalization of GPFM demonstrates its exceptional modeling capabilities across a wide range of clinical tasks, positioning it as a new cornerstone for feature representation in CPath.

Wearable devices record physiological and behavioral signals that can improve health predictions. While foundation models are increasingly used for such predictions, they have been primarily applied to low-level sensor data, despite behavioral data often being more informative due to their alignment with physiologically relevant timescales and quantities. We develop foundation models of such behavioral signals using over 2.5B hours of wearable data from 162K individuals, systematically optimizing architectures and tokenization strategies for this unique dataset. Evaluated on 57 health-related tasks, our model shows strong performance across diverse real-world applications including individual-level classification and time-varying health state prediction. The model excels in behavior-driven tasks like sleep prediction, and improves further when combined with representations of raw sensor data. These results underscore the importance of tailoring foundation model design to wearables and demonstrate the potential to enable new health applications.

Advances in foundation modeling have reshaped computational pathology. However, the increasing number of available models and lack of standardized benchmarks make it increasingly complex to assess their strengths, limitations, and potential for further development. To address these challenges, we introduce a new suite of software tools for whole-slide image processing, foundation model benchmarking, and curated publicly available tasks. We anticipate that these resources will promote transparency, reproducibility, and continued progress in the field.

Artificial intelligence (AI) has become a fundamental tool for assisting clinicians in analyzing ophthalmic images, such as optical coherence tomography (OCT). However, developing AI models often requires extensive annotation, and existing models tend to underperform on independent, unseen data. Foundation models (FMs), large AI models trained on vast unlabeled datasets, have shown promise in overcoming these challenges. Nonetheless, available FMs for ophthalmology lack extensive validation, especially for segmentation tasks, and focus on a single imaging modality. In this context, we propose MIRAGE, a novel multimodal FM for the analysis of OCT and scanning laser ophthalmoscopy (SLO) images. Additionally, we propose a new evaluation benchmark with OCT/SLO classification and segmentation tasks. The comparison with general and specialized FMs and segmentation methods shows the superiority of MIRAGE in both types of tasks, highlighting its suitability as a basis for the development of robust AI systems for retinal OCT image analysis. Both MIRAGE and the evaluation benchmark are publicly available: https://github.com/j-morano/MIRAGE.

We explore adapting foundation models (FMs) from the computer vision domain to geoscience. FMs, large neural networks trained on massive datasets, excel in diverse tasks with remarkable adaptability and generality. However, geoscience faces challenges like lacking curated training datasets and high computational costs for developing specialized FMs. This study considers adapting FMs from computer vision to geoscience, analyzing their scale, adaptability, and generality for geoscientific data analysis. We introduce a workflow that leverages existing computer vision FMs, fine-tuning them for geoscientific tasks, reducing development costs while enhancing accuracy. Through experiments, we demonstrate this workflow's effectiveness in broad applications to process and interpret geoscientific data of lunar images, seismic data, DAS arrays and so on. Our findings introduce advanced ML techniques to geoscience, proving the feasibility and advantages of cross-domain FMs adaptation, driving further advancements in geoscientific data analysis and offering valuable insights for FMs applications in other scientific domains.

Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. No systematic strategy currently exists to infer large-scale physical properties of a cell from its many molecular components. This is a significant obstacle to understanding biophysical processes such as cell adhesion and migration. Here, we develop a data-driven biophysical modeling approach to learn the mechanical behavior of adherent cells. We first train neural networks to predict forces generated by adherent cells from images of cytoskeletal proteins. Strikingly, experimental images of a single focal adhesion protein, such as zyxin, are sufficient to predict forces and generalize to unseen biological regimes. This protein field alone contains enough information to yield accurate predictions even if forces themselves are generated by many interacting proteins. We next develop two approaches - one explicitly constrained by physics, the other more agnostic - that help construct data-driven continuum models of cellular forces using this single focal adhesion field. Both strategies consistently reveal that cellular forces are encoded by two different length scales in adhesion protein distributions. Beyond adherent cell mechanics, our work serves as a case study for how to integrate neural networks in the construction of predictive phenomenological models in cell biology, even when little knowledge of the underlying microscopic mechanisms exist.

Traditional foundation models are pre-trained on broad datasets to reduce the training resources (e.g., time, energy, labeled samples) needed for fine-tuning a wide range of downstream tasks. However, traditional foundation models struggle with out-of-distribution prediction and can produce outputs that are unrealistic and physically infeasible. We propose the notation of physics-guided foundation models (PGFM), that is, foundation models integrated with broad or general domain (e.g., scientific) physical knowledge applicable to a wide range of downstream tasks.

Foundation models are rapidly being developed for computational pathology applications. However, it remains an open question which factors are most important for downstream performance with data scale and diversity, model size, and training algorithm all playing a role. In this work, we present the result of scaling both data and model size, surpassing previous studies in both dimensions, and introduce two new models: Virchow 2, a 632M parameter vision transformer, and Virchow 2G, a 1.85B parameter vision transformer, each trained with 3.1M histopathology whole slide images. To support this scale, we propose domain-inspired adaptations to the DINOv2 training algorithm, which is quickly becoming the default method in self-supervised learning for computational pathology. We achieve state of the art performance on twelve tile-level tasks, as compared to the top performing competing models. Our results suggest that data diversity and domain-specific training can outperform models that only scale in the number of parameters, but, on average, performance benefits from domain-tailoring, data scale, and model scale.

Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational dynamics. However, the capabilities and limitations associated with these models remain poorly understood due to the absence of a unified evaluation framework. To fill this gap, we introduce ProteinBench, a holistic evaluation framework designed to enhance the transparency of protein foundation models. Our approach consists of three key components: (i) A taxonomic classification of tasks that broadly encompass the main challenges in the protein domain, based on the relationships between different protein modalities; (ii) A multi-metric evaluation approach that assesses performance across four key dimensions: quality, novelty, diversity, and robustness; and (iii) In-depth analyses from various user objectives, providing a holistic view of model performance. Our comprehensive evaluation of protein foundation models reveals several key findings that shed light on their current capabilities and limitations. To promote transparency and facilitate further research, we release the evaluation dataset, code, and a public leaderboard publicly for further analysis and a general modular toolkit. We intend for ProteinBench to be a living benchmark for establishing a standardized, in-depth evaluation framework for protein foundation models, driving their development and application while fostering collaboration within the field.

Estimating single-cell responses across various perturbations facilitates the identification of key genes and enhances drug screening, significantly boosting experimental efficiency. However, single-cell sequencing is a destructive process, making it impossible to capture the same cell's phenotype before and after perturbation. Consequently, data collected under perturbed and unperturbed conditions are inherently unpaired. Existing methods either attempt to forcibly pair unpaired data using random sampling, or neglect the inherent relationship between unperturbed and perturbed cells during the modeling. In this work, we propose a framework based on Dual Diffusion Implicit Bridges (DDIB) to learn the mapping between different data distributions, effectively addressing the challenge of unpaired data. We further interpret this framework as a form of data augmentation. We integrate gene regulatory network (GRN) information to propagate perturbation signals in a biologically meaningful way, and further incorporate a masking mechanism to predict silent genes, improving the quality of generated profiles. Moreover, gene expression under the same perturbation often varies significantly across cells, frequently exhibiting a bimodal distribution that reflects intrinsic heterogeneity. To capture this, we introduce a more suitable evaluation metric. We propose Unlasting, dual conditional diffusion models that overcome the problem of unpaired single-cell perturbation data and strengthen the model's insight into perturbations under the guidance of the GRN, with a dedicated mask model designed to improve generation quality by predicting silent genes. In addition, we introduce a biologically grounded evaluation metric that better reflects the inherent heterogeneity in single-cell responses.

Foundation models have the potential to transform the landscape of remote sensing (RS) data analysis by enabling large computer vision models to be pre-trained on vast amounts of remote sensing data. These models can then be fine-tuned with small amounts of labeled training and applied to a variety of applications. Most existing foundation models are designed for high spatial resolution, cloud-free satellite imagery or photos, limiting their applicability in scenarios that require frequent temporal monitoring or broad spectral profiles. As a result, foundation models trained solely on cloud-free images have limited utility for applications that involve atmospheric variables or require atmospheric corrections. We introduce SatVision-TOA, a novel foundation model pre-trained on 14-band MODIS L1B Top-Of-Atmosphere (TOA) radiance imagery, addressing the need for models pre-trained to handle moderate- and coarse-resolution all-sky remote sensing data. The SatVision-TOA model is pre-trained using a Masked-Image-Modeling (MIM) framework and the SwinV2 architecture, and learns detailed contextual representations through self-supervised learning without the need for labels. It is a 3 billion parameter model that is trained on 100 million images. To our knowledge this is the largest foundation model trained solely on satellite RS imagery. Results show that SatVision-TOA achieves superior performance over baseline methods on downstream tasks such as 3D cloud retrieval. Notably, the model achieves a mean intersection over union (mIOU) of 0.46, a substantial improvement over the baseline mIOU of 0.22. Additionally, the rate of false negative results in the fine-tuning task were reduced by over 50% compared to the baseline. Our work advances pre-trained vision modeling for multispectral RS by learning from a variety of atmospheric and aerosol conditions to improve cloud and land surface monitoring.

AI-assisted radiological interpretation is based on predominantly narrow, single-task models. This approach is impractical for covering the vast spectrum of imaging modalities, diseases, and radiological findings. Foundation models (FMs) hold the promise of broad generalization across modalities and in low-data settings. However, this potential has remained largely unrealized in radiology. We introduce Curia, a foundation model trained on the entire cross-sectional imaging output of a major hospital over several years, which to our knowledge is the largest such corpus of real-world data-encompassing 150,000 exams (130 TB). On a newly curated 19-task external validation benchmark, Curia accurately identifies organs, detects conditions like brain hemorrhages and myocardial infarctions, and predicts outcomes in tumor staging. Curia meets or surpasses the performance of radiologists and recent foundation models, and exhibits clinically significant emergent properties in cross-modality, and low-data regimes. To accelerate progress, we release our base model's weights at https://huggingface.co/raidium/curia.

Over the past decade, the revolution in single-cell sequencing has enabled the simultaneous molecular profiling of various modalities across thousands of individual cells, allowing scientists to investigate the diverse functions of complex tissues and uncover underlying disease mechanisms. Among all the analytical steps, assigning individual cells to specific types is fundamental for understanding cellular heterogeneity. However, this process is usually labor-intensive and requires extensive expert knowledge. Recent advances in large language models (LLMs) have demonstrated their ability to efficiently process and synthesize vast corpora of text to automatically extract essential biological knowledge, such as marker genes, potentially promoting more efficient and automated cell type annotations. To thoroughly evaluate the capability of modern instruction-tuned LLMs in automating the cell type identification process, we introduce SOAR, a comprehensive benchmarking study of LLMs for cell type annotation tasks in single-cell genomics. Specifically, we assess the performance of 8 instruction-tuned LLMs across 11 datasets, spanning multiple cell types and species. Our study explores the potential of LLMs to accurately classify and annotate cell types in single-cell RNA sequencing (scRNA-seq) data, while extending their application to multiomics data through cross-modality translation. Additionally, we evaluate the effectiveness of chain-of-thought (CoT) prompting techniques in generating detailed biological insights during the annotation process. The results demonstrate that LLMs can provide robust interpretations of single-cell data without requiring additional fine-tuning, advancing the automation of cell type annotation in genomics research.

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding cell identity from the transcriptomic data, such as annotating cell types, has become an important task in bioinformatics. As these semantic aspects are determined by human experts, it is impossible for AI models to effectively carry out cell identity understanding tasks without the supervision signals provided by single-cell and label pairs. The single-cell pre-trained language models (PLMs) currently used for this task are trained only on a single modality, transcriptomics data, lack an understanding of cell identity knowledge. As a result, they have to be fine-tuned for downstream tasks and struggle when lacking labeled data with the desired semantic labels. To address this issue, we propose an innovative solution by constructing a unified representation of single-cell data and natural language during the pre-training phase, allowing the model to directly incorporate insights related to cell identity. More specifically, we introduce LangCell, the first Language-Cell pre-training framework. LangCell utilizes texts enriched with cell identity information to gain a profound comprehension of cross-modal knowledge. Results from experiments conducted on different benchmarks show that LangCell is the only single-cell PLM that can work effectively in zero-shot cell identity understanding scenarios, and also significantly outperforms existing models in few-shot and fine-tuning cell identity understanding scenarios.

Advancements in LLMs have recently unveiled challenges tied to computational efficiency and continual scalability due to their requirements of huge parameters, making the applications and evolution of these models on devices with limited computation resources and scenarios requiring various abilities increasingly cumbersome. Inspired by modularity within the human brain, there is a growing tendency to decompose LLMs into numerous functional modules, allowing for inference with part of modules and dynamic assembly of modules to tackle complex tasks, such as mixture-of-experts. To highlight the inherent efficiency and composability of the modular approach, we coin the term brick to represent each functional module, designating the modularized structure as configurable foundation models. In this paper, we offer a comprehensive overview and investigation of the construction, utilization, and limitation of configurable foundation models. We first formalize modules into emergent bricks - functional neuron partitions that emerge during the pre-training phase, and customized bricks - bricks constructed via additional post-training to improve the capabilities and knowledge of LLMs. Based on diverse functional bricks, we further present four brick-oriented operations: retrieval and routing, merging, updating, and growing. These operations allow for dynamic configuration of LLMs based on instructions to handle complex tasks. To verify our perspective, we conduct an empirical analysis on widely-used LLMs. We find that the FFN layers follow modular patterns with functional specialization of neurons and functional neuron partitions. Finally, we highlight several open issues and directions for future research. Overall, this paper aims to offer a fresh modular perspective on existing LLM research and inspire the future creation of more efficient and scalable foundational models.

Foundation model development attracts a rapidly expanding body of contributors, scientists, and applications. To help shape responsible development practices, we introduce the Foundation Model Development Cheatsheet: a growing collection of 250+ tools and resources spanning text, vision, and speech modalities. We draw on a large body of prior work to survey resources (e.g. software, documentation, frameworks, guides, and practical tools) that support informed data selection, processing, and understanding, precise and limitation-aware artifact documentation, efficient model training, advance awareness of the environmental impact from training, careful model evaluation of capabilities, risks, and claims, as well as responsible model release, licensing and deployment practices. We hope this curated collection of resources helps guide more responsible development. The process of curating this list, enabled us to review the AI development ecosystem, revealing what tools are critically missing, misused, or over-used in existing practices. We find that (i) tools for data sourcing, model evaluation, and monitoring are critically under-serving ethical and real-world needs, (ii) evaluations for model safety, capabilities, and environmental impact all lack reproducibility and transparency, (iii) text and particularly English-centric analyses continue to dominate over multilingual and multi-modal analyses, and (iv) evaluation of systems, rather than just models, is needed so that capabilities and impact are assessed in context.

Many cellular processes involve information processing and decision making. We can probe these processes at increasing molecular detail. The analysis of heterogeneous data remains a challenge that requires new ways of thinking about cells in quantitative, predictive, and mechanistic ways. We discuss the role of mathematical models in the context of cell-fate decision making systems across the tree of life. Complex multi-cellular organisms have been a particular focus, but single celled organisms also have to sense and respond to their environment. We center our discussion around the idea of design principles which we can learn from observations and modeling, and exploit in order to (re)-design or guide cellular behavior.

Foundation models pretrained on diverse data at scale have demonstrated extraordinary capabilities in a wide range of vision and language tasks. When such models are deployed in real world environments, they inevitably interface with other entities and agents. For example, language models are often used to interact with human beings through dialogue, and visual perception models are used to autonomously navigate neighborhood streets. In response to these developments, new paradigms are emerging for training foundation models to interact with other agents and perform long-term reasoning. These paradigms leverage the existence of ever-larger datasets curated for multimodal, multitask, and generalist interaction. Research at the intersection of foundation models and decision making holds tremendous promise for creating powerful new systems that can interact effectively across a diverse range of applications such as dialogue, autonomous driving, healthcare, education, and robotics. In this manuscript, we examine the scope of foundation models for decision making, and provide conceptual tools and technical background for understanding the problem space and exploring new research directions. We review recent approaches that ground foundation models in practical decision making applications through a variety of methods such as prompting, conditional generative modeling, planning, optimal control, and reinforcement learning, and discuss common challenges and open problems in the field.

In recent years, a plethora of open-source foundation models have emerged, achieving remarkable progress in some widely attended fields, with performance being quite close to that of closed-source models. However, in high-value but more challenging scientific professional fields, either the fields still rely on expert models, or the progress of general foundation models lags significantly compared to those in popular areas, far from sufficient for transforming scientific research and leaving substantial gap between open-source models and closed-source models in these scientific domains. To mitigate this gap and explore a step further toward Artificial General Intelligence (AGI), we introduce Intern-S1, a specialized generalist equipped with general understanding and reasoning capabilities with expertise to analyze multiple science modal data. Intern-S1 is a multimodal Mixture-of-Experts (MoE) model with 28 billion activated parameters and 241 billion total parameters, continually pre-trained on 5T tokens, including over 2.5T tokens from scientific domains. In the post-training stage, Intern-S1 undergoes offline and then online reinforcement learning (RL) in InternBootCamp, where we propose Mixture-of-Rewards (MoR) to synergize the RL training on more than 1000 tasks simultaneously. Through integrated innovations in algorithms, data, and training systems, Intern-S1 achieved top-tier performance in online RL training.On comprehensive evaluation benchmarks, Intern-S1 demonstrates competitive performance on general reasoning tasks among open-source models and significantly outperforms open-source models in scientific domains, surpassing closed-source state-of-the-art models in professional tasks, such as molecular synthesis planning, reaction condition prediction, predicting thermodynamic stabilities for crystals. Our models are available at https://huggingface.co/internlm/Intern-S1.

We introduce Orb-v3, the next generation of the Orb family of universal interatomic potentials. Models in this family expand the performance-speed-memory Pareto frontier, offering near SoTA performance across a range of evaluations with a >10x reduction in latency and > 8x reduction in memory. Our experiments systematically traverse this frontier, charting the trade-off induced by roto-equivariance, conservatism and graph sparsity. Contrary to recent literature, we find that non-equivariant, non-conservative architectures can accurately model physical properties, including those which require higher-order derivatives of the potential energy surface. This model release is guided by the principle that the most valuable foundation models for atomic simulation will excel on all fronts: accuracy, latency and system size scalability. The reward for doing so is a new era of computational chemistry driven by high-throughput and mesoscale all-atom simulations.

We survey applications of pretrained foundation models in robotics. Traditional deep learning models in robotics are trained on small datasets tailored for specific tasks, which limits their adaptability across diverse applications. In contrast, foundation models pretrained on internet-scale data appear to have superior generalization capabilities, and in some instances display an emergent ability to find zero-shot solutions to problems that are not present in the training data. Foundation models may hold the potential to enhance various components of the robot autonomy stack, from perception to decision-making and control. For example, large language models can generate code or provide common sense reasoning, while vision-language models enable open-vocabulary visual recognition. However, significant open research challenges remain, particularly around the scarcity of robot-relevant training data, safety guarantees and uncertainty quantification, and real-time execution. In this survey, we study recent papers that have used or built foundation models to solve robotics problems. We explore how foundation models contribute to improving robot capabilities in the domains of perception, decision-making, and control. We discuss the challenges hindering the adoption of foundation models in robot autonomy and provide opportunities and potential pathways for future advancements. The GitHub project corresponding to this paper (Preliminary release. We are committed to further enhancing and updating this work to ensure its quality and relevance) can be found here: https://github.com/robotics-survey/Awesome-Robotics-Foundation-Models

Computational microscopy, in which hardware and algorithms of an imaging system are jointly designed, shows promise for making imaging systems that cost less, perform more robustly, and collect new types of information. Often, the performance of computational imaging systems, especially those that incorporate machine learning, is sample-dependent. Thus, standardized datasets are an essential tool for comparing the performance of different approaches. Here, we introduce the Berkeley Single Cell Computational Microscopy (BSCCM) dataset, which contains over ~12,000,000 images of 400,000 of individual white blood cells. The dataset contains images captured with multiple illumination patterns on an LED array microscope and fluorescent measurements of the abundance of surface proteins that mark different cell types. We hope this dataset will provide a valuable resource for the development and testing of new algorithms in computational microscopy and computer vision with practical biomedical applications.

Foundation models are premised on the idea that sequence prediction can uncover deeper domain understanding, much like how Kepler's predictions of planetary motion later led to the discovery of Newtonian mechanics. However, evaluating whether these models truly capture deeper structure remains a challenge. We develop a technique for evaluating foundation models that examines how they adapt to synthetic datasets generated from some postulated world model. Our technique measures whether the foundation model's inductive bias aligns with the world model, and so we refer to it as an inductive bias probe. Across multiple domains, we find that foundation models can excel at their training tasks yet fail to develop inductive biases towards the underlying world model when adapted to new tasks. We particularly find that foundation models trained on orbital trajectories consistently fail to apply Newtonian mechanics when adapted to new physics tasks. Further analysis reveals that these models behave as if they develop task-specific heuristics that fail to generalize.

Recent advances in AI weather forecasting have led to the emergence of so-called "foundation models", typically defined by expensive pretraining and minimal fine-tuning for downstream tasks. However, in the natural sciences, a desirable foundation model should also encode meaningful statistical relationships between the underlying physical variables. This study evaluates the performance of the state-of-the-art Aurora foundation model in predicting hydrological variables, which were not considered during pretraining. We introduce a lightweight approach using shallow decoders trained on the latent representations of the pretrained model to predict these new variables. As a baseline, we compare this to fine-tuning the full model, which allows further optimization of the latent space while incorporating new variables into both inputs and outputs. The decoder-based approach requires 50% less training time and 35% less memory, while achieving strong accuracy across various hydrological variables and preserving desirable properties of the foundation model, such as autoregressive stability. Notably, decoder accuracy depends on the physical correlation between the new variables and those used during pretraining, indicating that Aurora's latent space captures meaningful physical relationships. In this sense, we argue that an important quality metric for foundation models in Earth sciences is their ability to be extended to new variables without a full fine-tuning. This provides a new perspective for making foundation models more accessible to communities with limited computational resources, while supporting broader adoption in Earth sciences.

Foundation models have shown remarkable success across scientific domains, yet their impact in chemistry remains limited due to the absence of diverse, large-scale, high-quality datasets that reflect the field's multifaceted nature. We present the ChemPile, an open dataset containing over 75 billion tokens of curated chemical data, specifically built for training and evaluating general-purpose models in the chemical sciences. The dataset mirrors the human learning journey through chemistry -- from educational foundations to specialized expertise -- spanning multiple modalities and content types including structured data in diverse chemical representations (SMILES, SELFIES, IUPAC names, InChI, molecular renderings), scientific and educational text, executable code, and chemical images. ChemPile integrates foundational knowledge (textbooks, lecture notes), specialized expertise (scientific articles and language-interfaced data), visual understanding (molecular structures, diagrams), and advanced reasoning (problem-solving traces and code) -- mirroring how human chemists develop expertise through diverse learning materials and experiences. Constructed through hundreds of hours of expert curation, the ChemPile captures both foundational concepts and domain-specific complexity. We provide standardized training, validation, and test splits, enabling robust benchmarking. ChemPile is openly released via HuggingFace with a consistent API, permissive license, and detailed documentation. We hope the ChemPile will serve as a catalyst for chemical AI, enabling the development of the next generation of chemical foundation models.

Single-cell RNA sequencing (scRNA-seq) data are often confounded by technical or biological batch effects. Existing deep learning models mitigate these effects but often discard batch-specific information, potentially losing valuable biological insights. We propose a Mixed Effects Deep Learning (MEDL) autoencoder framework that separately models batch-invariant (fixed effects) and batch-specific (random effects) components. By decoupling batch-invariant biological states from batch variations, our framework integrates both into predictive models. Our approach also generates 2D visualizations of how the same cell appears across batches, enhancing interpretability. Retaining both fixed and random effect latent spaces improves classification accuracy. We applied our framework to three datasets spanning the cardiovascular system (Healthy Heart), Autism Spectrum Disorder (ASD), and Acute Myeloid Leukemia (AML). With 147 batches in the Healthy Heart dataset, far exceeding typical numbers, we tested our framework's ability to handle many batches. In the ASD dataset, our approach captured donor heterogeneity between autistic and healthy individuals. In the AML dataset, it distinguished donor heterogeneity despite missing cell types and diseased donors exhibiting both healthy and malignant cells. These results highlight our framework's ability to characterize fixed and random effects, enhance batch effect visualization, and improve prediction accuracy across diverse datasets.

Foundation models are powerful technologies: how they are released publicly directly shapes their societal impact. In this position paper, we focus on open foundation models, defined here as those with broadly available model weights (e.g. Llama 2, Stable Diffusion XL). We identify five distinctive properties (e.g. greater customizability, poor monitoring) of open foundation models that lead to both their benefits and risks. Open foundation models present significant benefits, with some caveats, that span innovation, competition, the distribution of decision-making power, and transparency. To understand their risks of misuse, we design a risk assessment framework for analyzing their marginal risk. Across several misuse vectors (e.g. cyberattacks, bioweapons), we find that current research is insufficient to effectively characterize the marginal risk of open foundation models relative to pre-existing technologies. The framework helps explain why the marginal risk is low in some cases, clarifies disagreements about misuse risks by revealing that past work has focused on different subsets of the framework with different assumptions, and articulates a way forward for more constructive debate. Overall, our work helps support a more grounded assessment of the societal impact of open foundation models by outlining what research is needed to empirically validate their theoretical benefits and risks.

We present GeoGrid-Bench, a benchmark designed to evaluate the ability of foundation models to understand geo-spatial data in the grid structure. Geo-spatial datasets pose distinct challenges due to their dense numerical values, strong spatial and temporal dependencies, and unique multimodal representations including tabular data, heatmaps, and geographic visualizations. To assess how foundation models can support scientific research in this domain, GeoGrid-Bench features large-scale, real-world data covering 16 climate variables across 150 locations and extended time frames. The benchmark includes approximately 3,200 question-answer pairs, systematically generated from 8 domain expert-curated templates to reflect practical tasks encountered by human scientists. These range from basic queries at a single location and time to complex spatiotemporal comparisons across regions and periods. Our evaluation reveals that vision-language models perform best overall, and we provide a fine-grained analysis of the strengths and limitations of different foundation models in different geo-spatial tasks. This benchmark offers clearer insights into how foundation models can be effectively applied to geo-spatial data analysis and used to support scientific research.

Rapid progress in computational pathology is increasingly driven by vision foundation models pretrained on vast histopathology datasets. While recent efforts have prioritized training on an ever-larger amount of patches, we take an alternative approach focused on data diversity. Our foundation model, Athena, was initialized from a pretrained model and trained on just 115 million tissue patches, several times fewer than recent histopathology foundation models. Rather than relying on patch volume or complex sampling heuristics, we maximize data diversity by randomly selecting only a moderate number of patches per whole-slide image from our diverse internal repository, which spans multiple countries, institutions, and scanner types. Evaluated on a single patch-level benchmark and four slide-level downstream tasks (two molecular and two morphological), Athena approaches the state-of-the-art and even surpasses several models trained on substantially larger datasets. This indicates that diversity across whole-slide images, rather than patch quantity alone, drives learning in histopathology foundation models.

This position paper explores the rapid development of Foundation Models (FMs) in AI and their implications for intelligence and reasoning. It examines the characteristics of FMs, including their training on vast datasets and use of embedding spaces to capture semantic relationships. The paper discusses recent advancements in FMs' reasoning abilities which we argue cannot be attributed to increased model size but to novel training techniques which yield learning phenomena like grokking. It also addresses the challenges in benchmarking FMs and compares their structure to the human brain. We argue that while FMs show promising developments in reasoning and knowledge representation, understanding their inner workings remains a significant challenge, similar to ongoing efforts in neuroscience to comprehend human brain function. Despite having some similarities, fundamental differences between FMs and the structure of human brain warn us against making direct comparisons or expecting neuroscience to provide immediate insights into FM function.

Pre-trained language models (PLMs) have revolutionized scientific research, yet their application to single-cell analysis remains limited. Text PLMs cannot process single-cell RNA sequencing data, while cell PLMs lack the ability to handle free text, restricting their use in multimodal tasks. Existing efforts to bridge these modalities often suffer from information loss or inadequate single-modal pre-training, leading to suboptimal performances. To address these challenges, we propose Single-Cell MultiModal Generative Pre-trained Transformer (scMMGPT), a unified PLM for joint cell and text modeling. scMMGPT effectively integrates the state-of-the-art cell and text PLMs, facilitating cross-modal knowledge sharing for improved performance. To bridge the text-cell modality gap, scMMGPT leverages dedicated cross-modal projectors, and undergoes extensive pre-training on 27 million cells -- the largest dataset for multimodal cell-text PLMs to date. This large-scale pre-training enables scMMGPT to excel in joint cell-text tasks, achieving an 84\% relative improvement of textual discrepancy for cell description generation, 20.5\% higher accuracy for cell type annotation, and 4\% improvement in k-NN accuracy for text-conditioned pseudo-cell generation, outperforming baselines.

Recent advancements in digital pathology have led to the development of numerous foundational models that utilize self-supervised learning on patches extracted from gigapixel whole slide images (WSIs). While this approach leverages vast amounts of unlabeled data, we have discovered a significant issue: features extracted from these self-supervised models tend to cluster by individual WSIs, a phenomenon we term WSI-specific feature collapse. This problem can potentially limit the model's generalization ability and performance on various downstream tasks. To address this issue, we introduce Stain Normalized Pathology Foundational Model, a novel foundational model trained on patches that have undergone stain normalization. Stain normalization helps reduce color variability arising from different laboratories and scanners, enabling the model to learn more consistent features. Stain Normalized Pathology Foundational Model is trained using 285,153,903 patches extracted from a total of 34,795 WSIs, combining data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Our experiments demonstrate that Stain Normalized Pathology Foundational Model significantly mitigates the feature collapse problem, indicating that the model has learned more generalized features rather than overfitting to individual WSI characteristics. We compared Stain Normalized Pathology Foundational Model with state-of-the-art models across six downstream task datasets, and our results show that Stain Normalized Pathology Foundational Model achieves excellent performance relative to the number of WSIs used and the model's parameter count. This suggests that the application of stain normalization has substantially improved the model's efficiency and generalization capabilities.

Foundation models for interactive segmentation in 2D natural images and videos have sparked significant interest in building 3D foundation models for medical imaging. However, the domain gaps and clinical use cases for 3D medical imaging require a dedicated model that diverges from existing 2D solutions. Specifically, such foundation models should support a full workflow that can actually reduce human effort. Treating 3D medical images as sequences of 2D slices and reusing interactive 2D foundation models seems straightforward, but 2D annotation is too time-consuming for 3D tasks. Moreover, for large cohort analysis, it's the highly accurate automatic segmentation models that reduce the most human effort. However, these models lack support for interactive corrections and lack zero-shot ability for novel structures, which is a key feature of "foundation". While reusing pre-trained 2D backbones in 3D enhances zero-shot potential, their performance on complex 3D structures still lags behind leading 3D models. To address these issues, we present VISTA3D, Versatile Imaging SegmenTation and Annotation model, that targets to solve all these challenges and requirements with one unified foundation model. VISTA3D is built on top of the well-established 3D segmentation pipeline, and it is the first model to achieve state-of-the-art performance in both 3D automatic (supporting 127 classes) and 3D interactive segmentation, even when compared with top 3D expert models on large and diverse benchmarks. Additionally, VISTA3D's 3D interactive design allows efficient human correction, and a novel 3D supervoxel method that distills 2D pretrained backbones grants VISTA3D top 3D zero-shot performance. We believe the model, recipe, and insights represent a promising step towards a clinically useful 3D foundation model. Code and weights are publicly available at https://github.com/Project-MONAI/VISTA.

The code of nature, embedded in DNA and RNA genomes since the origin of life, holds immense potential to impact both humans and ecosystems through genome modeling. Genomic Foundation Models (GFMs) have emerged as a transformative approach to decoding the genome. As GFMs scale up and reshape the landscape of AI-driven genomics, the field faces an urgent need for rigorous and reproducible evaluation. We present OmniGenBench, a modular benchmarking platform designed to unify the data, model, benchmarking, and interpretability layers across GFMs. OmniGenBench enables standardized, one-command evaluation of any GFM across five benchmark suites, with seamless integration of over 31 open-source models. Through automated pipelines and community-extensible features, the platform addresses critical reproducibility challenges, including data transparency, model interoperability, benchmark fragmentation, and black-box interpretability. OmniGenBench aims to serve as foundational infrastructure for reproducible genomic AI research, accelerating trustworthy discovery and collaborative innovation in the era of genome-scale modeling.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

Segmenting 3D blood vessels is a critical yet challenging task in medical image analysis. This is due to significant imaging modality-specific variations in artifacts, vascular patterns and scales, signal-to-noise ratios, and background tissues. These variations, along with domain gaps arising from varying imaging protocols, limit the generalization of existing supervised learning-based methods, requiring tedious voxel-level annotations for each dataset separately. While foundation models promise to alleviate this limitation, they typically fail to generalize to the task of blood vessel segmentation, posing a unique, complex problem. In this work, we present vesselFM, a foundation model designed specifically for the broad task of 3D blood vessel segmentation. Unlike previous models, vesselFM can effortlessly generalize to unseen domains. To achieve zero-shot generalization, we train vesselFM on three heterogeneous data sources: a large, curated annotated dataset, data generated by a domain randomization scheme, and data sampled from a flow matching-based generative model. Extensive evaluations show that vesselFM outperforms state-of-the-art medical image segmentation foundation models across four (pre-)clinically relevant imaging modalities in zero-, one-, and few-shot scenarios, therefore providing a universal solution for 3D blood vessel segmentation.

Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.

The development of foundation models has revolutionized our ability to interpret the Earth's surface using satellite observational data. Traditional models have been siloed, tailored to specific sensors or data types like optical, radar, and hyperspectral, each with its own unique characteristics. This specialization hinders the potential for a holistic analysis that could benefit from the combined strengths of these diverse data sources. Our novel approach introduces the Dynamic One-For-All (DOFA) model, leveraging the concept of neural plasticity in brain science to integrate various data modalities into a single framework adaptively. This dynamic hypernetwork, adjusting to different wavelengths, enables a single versatile Transformer jointly trained on data from five sensors to excel across 12 distinct Earth observation tasks, including sensors never seen during pretraining. DOFA's innovative design offers a promising leap towards more accurate, efficient, and unified Earth observation analysis, showcasing remarkable adaptability and performance in harnessing the potential of multimodal Earth observation data.

Foundation models (FMs) are pre-trained on large-scale datasets and then fine-tuned on a downstream task for a specific application. The most successful and most commonly used fine-tuning method is to update the pre-trained weights via a low-rank adaptation (LoRA). LoRA introduces new weight matrices that are usually initialized at random with a uniform rank distribution across model weights. Recent works focus on weight-driven initialization or learning of adaptive ranks during training. Both approaches have only been investigated in isolation, resulting in slow convergence or a uniform rank distribution, in turn leading to sub-optimal performance. We propose to enhance LoRA by initializing the new weights in a data-driven manner by computing singular value decomposition on minibatches of activation vectors. Then, we initialize the LoRA matrices with the obtained right-singular vectors and re-distribute ranks among all weight matrices to explain the maximal amount of variance and continue the standard LoRA fine-tuning procedure. This results in our new method Explained Variance Adaptation (EVA). We apply EVA to a variety of fine-tuning tasks ranging from language generation and understanding to image classification and reinforcement learning. EVA exhibits faster convergence than competitors and attains the highest average score across a multitude of tasks per domain.

Biological tissues exhibit complex behaviors with their dynamics often resembling inert soft matter such as liquids, polymers, colloids, and liquid crystals. These analogies enable physics-based approaches for investigations of emergent behaviors in biological processes. A well-studied case is the spreading of cellular aggregates on solid surfaces, where they display dynamics similar to viscous droplets. In vivo, however, cells and tissues are in a confined environment with varying geometries and mechanical properties to which they need to adapt. In this work, we compressed cellular aggregates between two solid surfaces and studied their dynamics using microscopy, and computer simulations. The confined cellular aggregates transitioned from compressed spheres into dynamic living capillary bridges exhibiting bridge thinning and a convex-to-concave meniscus curvature transition. We found that the stability of the bridge is determined by the interplay between cell growth and cell spreading on the confining surfaces. This interaction leads to bridge rupture at a critical length scale determined by the distance between the plates. The force distributions, formation and stability regimes of the living capillary bridges were characterized with full 3D computer simulations that included cell division, migration and growth dynamics, directly showing how mechanical principles govern the behavior of the living bridges; cellular aggregates display jamming and stiffening analogously to granular matter, and cell division along the long axis enhances thinning. Based on our results, we propose a new class of active soft matter behavior, where cellular aggregates exhibit liquid-like adaptation to confinement, but with self-organized rupturing driven by biological activity.

Large foundation models, including large language models (LLMs), vision transformers (ViTs), diffusion, and LLM-based multimodal models, are revolutionizing the entire machine learning lifecycle, from training to deployment. However, the substantial advancements in versatility and performance these models offer come at a significant cost in terms of hardware resources. To support the growth of these large models in a scalable and environmentally sustainable way, there has been a considerable focus on developing resource-efficient strategies. This survey delves into the critical importance of such research, examining both algorithmic and systemic aspects. It offers a comprehensive analysis and valuable insights gleaned from existing literature, encompassing a broad array of topics from cutting-edge model architectures and training/serving algorithms to practical system designs and implementations. The goal of this survey is to provide an overarching understanding of how current approaches are tackling the resource challenges posed by large foundation models and to potentially inspire future breakthroughs in this field.

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

The rise of imaging techniques such as optical coherence tomography (OCT) and advances in deep learning (DL) have enabled clinicians and researchers to streamline retinal disease staging. A popular DL approach is self-supervised learning (SSL), where models learn from vast amounts of unlabeled data, avoiding costly annotation. SSL has allowed the development of foundation models (FMs), large models that can be used for a variety of downstream tasks. However, existing FMs for OCT, trained solely on image data, lack a comprehensive and robust semantic understanding of images, as evidenced by their downstream performance (especially for complex tasks), and thus require supervised fine-tuning (which may be unfeasible) to better adapt to specific applications and populations. To address this, we propose RetFiner, an SSL vision-language refinement scheme that improves the representations of existing FMs and enables their efficient and direct adaptation to specific populations for improved downstream performance. Our method uses a diverse set of training objectives which take advantage of the rich supervisory signal found in textual data. We tested RetFiner on the retinal FMs RETFound, UrFound, and VisionFM, showing significant improvements in linear probing performance on seven highly diverse OCT classification tasks, with an average increase of 5.8, 3.9, and 2.1 percentage points over their baselines, respectively. Our code and model weights are publicly available at https://github.com/ronnief1/RetFiner.

Sparse autoencoders (SAEs) emerged as a promising tool for mechanistic interpretability of transformer-based foundation models. Very recently, SAEs were also adopted for the visual domain, enabling the discovery of visual concepts and their patch-wise attribution to tokens in the transformer model. While a growing number of foundation models emerged for medical imaging, tools for explaining their inferences are still lacking. In this work, we show the applicability of SAEs for hematology. We propose CytoSAE, a sparse autoencoder which is trained on over 40,000 peripheral blood single-cell images. CytoSAE generalizes to diverse and out-of-domain datasets, including bone marrow cytology, where it identifies morphologically relevant concepts which we validated with medical experts. Furthermore, we demonstrate scenarios in which CytoSAE can generate patient-specific and disease-specific concepts, enabling the detection of pathognomonic cells and localized cellular abnormalities at the patch level. We quantified the effect of concepts on a patient-level AML subtype classification task and show that CytoSAE concepts reach performance comparable to the state-of-the-art, while offering explainability on the sub-cellular level. Source code and model weights are available at https://github.com/dynamical-inference/cytosae.

Conventional task-specific electrocardiogram (ECG) analysis models require large annotated datasets to train. Foundation models mitigate this burden by leveraging self-supervised pretraining; however, the scarcity of open-weight ECG foundation models hinders adoption and cross-study comparability. We present ECG-FM, an open foundation model for ECG analysis, and conduct a study using a dataset of 1.5 million ECGs. ECG-FM is a transformer-based model pretrained using a hybrid contrastive and generative self-supervised learning approach. Our downstream tasks include predicting reduced left ventricular ejection fraction (LVEF) and ECG interpretation labels, where we release a benchmark task on the MIMIC-IV-ECG dataset. We affirm that ECG-FM is robust, label-efficient, and functionally discriminative by showcasing data scaling experiments, performing a latent space analysis, and generating saliency maps. ECG-FM markedly outperforms task-specific models in the small-to-medium-scale data regime and demonstrates cross-dataset generalizability, achieving high AUROC on many clinically salient labels such as atrial fibrillation (0.996) and LVEF<=40% (0.929). We release our code, model weights, and benchmark task at https://github.com/bowang-lab/ECG-FM/.

As a powerful tool for characterizing cellular subpopulations and cellular heterogeneity, single cell RNA sequencing (scRNA-seq) technology offers advantages of high throughput and multidimensional analysis. However, the process of data acquisition is often constrained by high cost and limited sample availability. To overcome these limitations, we propose a hybrid model based on Diffusion model and White-Box transformer that aims to generate synthetic and biologically plausible scRNA-seq data. Diffusion model progressively introduce noise into the data and then recover the original data through a denoising process, a forward and reverse process that is particularly suitable for generating complex data distributions. White-Box transformer is a deep learning architecture that emphasizes mathematical interpretability. By minimizing the encoding rate of the data and maximizing the sparsity of the representation, it not only reduces the computational burden, but also provides clear insight into underlying structure. Our White-Box Diffusion Transformer combines the generative capabilities of Diffusion model with the mathematical interpretability of White-Box transformer. Through experiments using six different single-cell RNA-Seq datasets, we visualize both generated and real data using t-SNE dimensionality reduction technique, as well as quantify similarity between generated and real data using various metrics to demonstrate comparable performance of White-Box Diffusion Transformer and Diffusion Transformer in generating scRNA-seq data alongside significant improvements in training efficiency and resource utilization. Our code is available at https://github.com/lingximamo/White-Box-Diffusion-Transformer

Practitioners frequently aim to infer an unobserved population trajectory using sample snapshots at multiple time points. For instance, in single-cell sequencing, scientists would like to learn how gene expression evolves over time. But sequencing any cell destroys that cell. So we cannot access any cell's full trajectory, but we can access snapshot samples from many cells. Stochastic differential equations are commonly used to analyze systems with full individual-trajectory access; since here we have only sample snapshots, these methods are inapplicable. The deep learning community has recently explored using Schr\"odinger bridges (SBs) and their extensions to estimate these dynamics. However, these methods either (1) interpolate between just two time points or (2) require a single fixed reference dynamic within the SB, which is often just set to be Brownian motion. But learning piecewise from adjacent time points can fail to capture long-term dependencies. And practitioners are typically able to specify a model class for the reference dynamic but not the exact values of the parameters within it. So we propose a new method that (1) learns the unobserved trajectories from sample snapshots across multiple time points and (2) requires specification only of a class of reference dynamics, not a single fixed one. In particular, we suggest an iterative projection method inspired by Schr\"odinger bridges; we alternate between learning a piecewise SB on the unobserved trajectories and using the learned SB to refine our best guess for the dynamics within the reference class. We demonstrate the advantages of our method via a well-known simulated parametric model from ecology, simulated and real data from systems biology, and real motion-capture data.

Histopathology plays a central role in clinical medicine and biomedical research. While artificial intelligence shows promising results on many pathological tasks, generalization and dealing with rare diseases, where training data is scarce, remains a challenge. Distilling knowledge from unlabeled data into a foundation model before learning from, potentially limited, labeled data provides a viable path to address these challenges. In this work, we extend the state of the art of foundation models for digital pathology whole slide images by semi-automated data curation and incorporating pathologist domain knowledge. Specifically, we combine computational and pathologist domain knowledge (1) to curate a diverse dataset of 103k slides corresponding to 750 million image patches covering data from different fixation, staining, and scanning protocols as well as data from different indications and labs across the EU and US, (2) for grouping semantically similar slides and tissue patches, and (3) to augment the input images during training. We evaluate the resulting model on a set of public and internal benchmarks and show that although our foundation model is trained with an order of magnitude less slides, it performs on par or better than competing models. We expect that scaling our approach to more data and larger models will further increase its performance and capacity to deal with increasingly complex real world tasks in diagnostics and biomedical research.

Foundation models have demonstrated remarkable success across various scientific domains, motivating our exploration of their potential in solar physics. In this paper, we present Solaris, the first foundation model for forecasting the Sun's atmosphere. We leverage 13 years of full-disk, multi-wavelength solar imagery from the Solar Dynamics Observatory, spanning a complete solar cycle, to pre-train Solaris for 12-hour interval forecasting. Solaris is built on a large-scale 3D Swin Transformer architecture with 109 million parameters. We demonstrate Solaris' ability to generalize by fine-tuning on a low-data regime using a single wavelength (1700 {\AA}), that was not included in pre-training, outperforming models trained from scratch on this specific wavelength. Our results indicate that Solaris can effectively capture the complex dynamics of the solar atmosphere and transform solar forecasting.

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab.

Cell instance segmentation is a fundamental task in digital pathology with broad clinical applications. Recently, vision foundation models, which are predominantly based on Vision Transformers (ViTs), have achieved remarkable success in pathology image analysis. However, their improvements in cell instance segmentation remain limited. A key challenge arises from the tokenization process in ViTs, which substantially reduces the spatial resolution of input images, leading to suboptimal segmentation quality, especially for small and densely packed cells. To address this problem, we propose CellVTA (Cell Vision Transformer with Adapter), a novel method that improves the performance of vision foundation models for cell instance segmentation by incorporating a CNN-based adapter module. This adapter extracts high-resolution spatial information from input images and injects it into the ViT through a cross-attention mechanism. Our method preserves the core architecture of ViT, ensuring seamless integration with pretrained foundation models. Extensive experiments show that CellVTA achieves 0.538 mPQ on the CoNIC dataset and 0.506 mPQ on the PanNuke dataset, which significantly outperforms the state-of-the-art cell segmentation methods. Ablation studies confirm the superiority of our approach over other fine-tuning strategies, including decoder-only fine-tuning and full fine-tuning. Our code and models are publicly available at https://github.com/JieZheng-ShanghaiTech/CellVTA.

Non-coding RNA structure and function are essential to understanding various biological processes, such as cell signaling, gene expression, and post-transcriptional regulations. These are all among the core problems in the RNA field. With the rapid growth of sequencing technology, we have accumulated a massive amount of unannotated RNA sequences. On the other hand, expensive experimental observatory results in only limited numbers of annotated data and 3D structures. Hence, it is still challenging to design computational methods for predicting their structures and functions. The lack of annotated data and systematic study causes inferior performance. To resolve the issue, we propose a novel RNA foundation model (RNA-FM) to take advantage of all the 23 million non-coding RNA sequences through self-supervised learning. Within this approach, we discover that the pre-trained RNA-FM could infer sequential and evolutionary information of non-coding RNAs without using any labels. Furthermore, we demonstrate RNA-FM's effectiveness by applying it to the downstream secondary/3D structure prediction, SARS-CoV-2 genome structure and evolution prediction, protein-RNA binding preference modeling, and gene expression regulation modeling. The comprehensive experiments show that the proposed method improves the RNA structural and functional modelling results significantly and consistently. Despite only being trained with unlabelled data, RNA-FM can serve as the foundational model for the field.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

We propose PROSE-FD, a zero-shot multimodal PDE foundational model for simultaneous prediction of heterogeneous two-dimensional physical systems related to distinct fluid dynamics settings. These systems include shallow water equations and the Navier-Stokes equations with incompressible and compressible flow, regular and complex geometries, and different buoyancy settings. This work presents a new transformer-based multi-operator learning approach that fuses symbolic information to perform operator-based data prediction, i.e. non-autoregressive. By incorporating multiple modalities in the inputs, the PDE foundation model builds in a pathway for including mathematical descriptions of the physical behavior. We pre-train our foundation model on 6 parametric families of equations collected from 13 datasets, including over 60K trajectories. Our model outperforms popular operator learning, computer vision, and multi-physics models, in benchmark forward prediction tasks. We test our architecture choices with ablation studies.

Machine-learned force fields have transformed the atomistic modelling of materials by enabling simulations of ab initio quality on unprecedented time and length scales. However, they are currently limited by: (i) the significant computational and human effort that must go into development and validation of potentials for each particular system of interest; and (ii) a general lack of transferability from one chemical system to the next. Here, using the state-of-the-art MACE architecture we introduce a single general-purpose ML model, trained on a public database of 150k inorganic crystals, that is capable of running stable molecular dynamics on molecules and materials. We demonstrate the power of the MACE-MP-0 model -- and its qualitative and at times quantitative accuracy -- on a diverse set problems in the physical sciences, including the properties of solids, liquids, gases, and chemical reactions. The model can be applied out of the box and as a starting or "foundation model" for any atomistic system of interest and is thus a step towards democratising the revolution of ML force fields by lowering the barriers to entry.

This work addresses the task of zero-shot monocular depth estimation. A recent advance in this field has been the idea of utilising Text-to-Image foundation models, such as Stable Diffusion. Foundation models provide a rich and generic image representation, and therefore, little training data is required to reformulate them as a depth estimation model that predicts highly-detailed depth maps and has good generalisation capabilities. However, the realisation of this idea has so far led to approaches which are, unfortunately, highly inefficient at test-time due to the underlying iterative denoising process. In this work, we propose a different realisation of this idea and present PrimeDepth, a method that is highly efficient at test time while keeping, or even enhancing, the positive aspects of diffusion-based approaches. Our key idea is to extract from Stable Diffusion a rich, but frozen, image representation by running a single denoising step. This representation, we term preimage, is then fed into a refiner network with an architectural inductive bias, before entering the downstream task. We validate experimentally that PrimeDepth is two orders of magnitude faster than the leading diffusion-based method, Marigold, while being more robust for challenging scenarios and quantitatively marginally superior. Thereby, we reduce the gap to the currently leading data-driven approach, Depth Anything, which is still quantitatively superior, but predicts less detailed depth maps and requires 20 times more labelled data. Due to the complementary nature of our approach, even a simple averaging between PrimeDepth and Depth Anything predictions can improve upon both methods and sets a new state-of-the-art in zero-shot monocular depth estimation. In future, data-driven approaches may also benefit from integrating our preimage.

Significant progress in the development of highly adaptable and reusable Artificial Intelligence (AI) models is expected to have a significant impact on Earth science and remote sensing. Foundation models are pre-trained on large unlabeled datasets through self-supervision, and then fine-tuned for various downstream tasks with small labeled datasets. This paper introduces a first-of-a-kind framework for the efficient pre-training and fine-tuning of foundational models on extensive geospatial data. We have utilized this framework to create Prithvi, a transformer-based geospatial foundational model pre-trained on more than 1TB of multispectral satellite imagery from the Harmonized Landsat-Sentinel 2 (HLS) dataset. Our study demonstrates the efficacy of our framework in successfully fine-tuning Prithvi to a range of Earth observation tasks that have not been tackled by previous work on foundation models involving multi-temporal cloud gap imputation, flood mapping, wildfire scar segmentation, and multi-temporal crop segmentation. Our experiments show that the pre-trained model accelerates the fine-tuning process compared to leveraging randomly initialized weights. In addition, pre-trained Prithvi compares well against the state-of-the-art, e.g., outperforming a conditional GAN model in multi-temporal cloud imputation by up to 5pp (or 5.7%) in the structural similarity index. Finally, due to the limited availability of labeled data in the field of Earth observation, we gradually reduce the quantity of available labeled data for refining the model to evaluate data efficiency and demonstrate that data can be decreased significantly without affecting the model's accuracy. The pre-trained 100 million parameter model and corresponding fine-tuning workflows have been released publicly as open source contributions to the global Earth sciences community through Hugging Face.

This open access book provides a comprehensive overview of the state of the art in research and applications of Foundation Models and is intended for readers familiar with basic Natural Language Processing (NLP) concepts. Over the recent years, a revolutionary new paradigm has been developed for training models for NLP. These models are first pre-trained on large collections of text documents to acquire general syntactic knowledge and semantic information. Then, they are fine-tuned for specific tasks, which they can often solve with superhuman accuracy. When the models are large enough, they can be instructed by prompts to solve new tasks without any fine-tuning. Moreover, they can be applied to a wide range of different media and problem domains, ranging from image and video processing to robot control learning. Because they provide a blueprint for solving many tasks in artificial intelligence, they have been called Foundation Models. After a brief introduction to basic NLP models the main pre-trained language models BERT, GPT and sequence-to-sequence transformer are described, as well as the concepts of self-attention and context-sensitive embedding. Then, different approaches to improving these models are discussed, such as expanding the pre-training criteria, increasing the length of input texts, or including extra knowledge. An overview of the best-performing models for about twenty application areas is then presented, e.g., question answering, translation, story generation, dialog systems, generating images from text, etc. For each application area, the strengths and weaknesses of current models are discussed, and an outlook on further developments is given. In addition, links are provided to freely available program code. A concluding chapter summarizes the economic opportunities, mitigation of risks, and potential developments of AI.

Foundation models have emerged as critical components in a variety of artificial intelligence applications, and showcase significant success in natural language processing and several other domains. Meanwhile, the field of graph machine learning is witnessing a paradigm transition from shallow methods to more sophisticated deep learning approaches. The capabilities of foundation models to generalize and adapt motivate graph machine learning researchers to discuss the potential of developing a new graph learning paradigm. This paradigm envisions models that are pre-trained on extensive graph data and can be adapted for various graph tasks. Despite this burgeoning interest, there is a noticeable lack of clear definitions and systematic analyses pertaining to this new domain. To this end, this article introduces the concept of Graph Foundation Models (GFMs), and offers an exhaustive explanation of their key characteristics and underlying technologies. We proceed to classify the existing work related to GFMs into three distinct categories, based on their dependence on graph neural networks and large language models. In addition to providing a thorough review of the current state of GFMs, this article also outlooks potential avenues for future research in this rapidly evolving domain.

The advent of foundation models has revolutionized the fields of natural language processing and computer vision, paving the way for their application in autonomous driving (AD). This survey presents a comprehensive review of more than 40 research papers, demonstrating the role of foundation models in enhancing AD. Large language models contribute to planning and simulation in AD, particularly through their proficiency in reasoning, code generation and translation. In parallel, vision foundation models are increasingly adapted for critical tasks such as 3D object detection and tracking, as well as creating realistic driving scenarios for simulation and testing. Multi-modal foundation models, integrating diverse inputs, exhibit exceptional visual understanding and spatial reasoning, crucial for end-to-end AD. This survey not only provides a structured taxonomy, categorizing foundation models based on their modalities and functionalities within the AD domain but also delves into the methods employed in current research. It identifies the gaps between existing foundation models and cutting-edge AD approaches, thereby charting future research directions and proposing a roadmap for bridging these gaps.

Many real-world problems require reasoning across multiple scales, demanding models which operate not on single data points, but on entire distributions. We introduce generative distribution embeddings (GDE), a framework that lifts autoencoders to the space of distributions. In GDEs, an encoder acts on sets of samples, and the decoder is replaced by a generator which aims to match the input distribution. This framework enables learning representations of distributions by coupling conditional generative models with encoder networks which satisfy a criterion we call distributional invariance. We show that GDEs learn predictive sufficient statistics embedded in the Wasserstein space, such that latent GDE distances approximately recover the W_2 distance, and latent interpolation approximately recovers optimal transport trajectories for Gaussian and Gaussian mixture distributions. We systematically benchmark GDEs against existing approaches on synthetic datasets, demonstrating consistently stronger performance. We then apply GDEs to six key problems in computational biology: learning representations of cell populations from lineage-tracing data (150K cells), predicting perturbation effects on single-cell transcriptomes (1M cells), predicting perturbation effects on cellular phenotypes (20M single-cell images), modeling tissue-specific DNA methylation patterns (253M sequences), designing synthetic yeast promoters (34M sequences), and spatiotemporal modeling of viral protein sequences (1M sequences).

Medical image segmentation and video object segmentation are essential for diagnosing and analyzing diseases by identifying and measuring biological structures. Recent advances in natural domain have been driven by foundation models like the Segment Anything Model 2 (SAM 2). To explore the performance of SAM 2 in biomedical applications, we designed two evaluation pipelines for single-frame image segmentation and multi-frame video segmentation with varied prompt designs, revealing SAM 2's limitations in medical contexts. Consequently, we developed BioSAM 2, an enhanced foundation model optimized for biomedical data based on SAM 2. Our experiments show that BioSAM 2 not only surpasses the performance of existing state-of-the-art foundation models but also matches or even exceeds specialist models, demonstrating its efficacy and potential in the medical domain.

Foundation models are redefining how AI systems are built. Practitioners now follow a standard procedure to build their machine learning solutions: from a pre-trained foundation model, they fine-tune the weights on the target task of interest. So, the Internet is swarmed by a handful of foundation models fine-tuned on many diverse tasks: these individual fine-tunings exist in isolation without benefiting from each other. In our opinion, this is a missed opportunity, as these specialized models contain rich and diverse features. In this paper, we thus propose model ratatouille, a new strategy to recycle the multiple fine-tunings of the same foundation model on diverse auxiliary tasks. Specifically, we repurpose these auxiliary weights as initializations for multiple parallel fine-tunings on the target task; then, we average all fine-tuned weights to obtain the final model. This recycling strategy aims at maximizing the diversity in weights by leveraging the diversity in auxiliary tasks. Empirically, it improves the state of the art on the reference DomainBed benchmark for out-of-distribution generalization. Looking forward, this work contributes to the emerging paradigm of updatable machine learning where, akin to open-source software development, the community collaborates to reliably update machine learning models.

Although Foundation Models (FMs), such as GPT-4, are increasingly used in domains like finance and software engineering, reliance on textual interfaces limits these models' real-world interaction. To address this, FM providers introduced tool calling-triggering a proliferation of frameworks with distinct tool interfaces. In late 2024, Anthropic introduced the Model Context Protocol (MCP) to standardize this tool ecosystem, which has become the de facto standard with over eight million weekly SDK downloads. Despite its adoption, MCP's AI-driven, non-deterministic control flow introduces new risks to sustainability, security, and maintainability, warranting closer examination. Towards this end, we present the first large-scale empirical study of MCP servers. Using state-of-the-art health metrics and a hybrid analysis pipeline, combining a general-purpose static analysis tool with an MCP-specific scanner, we evaluate 1,899 open-source MCP servers to assess their health, security, and maintainability. Despite MCP servers demonstrating strong health metrics, we identify eight distinct vulnerabilities - only three overlapping with traditional software vulnerabilities. Additionally, 7.2% of servers contain general vulnerabilities and 5.5% exhibit MCP-specific tool poisoning. Regarding maintainability, while 66% exhibit code smells, 14.4% contain nine bug patterns overlapping with traditional open-source software projects. These findings highlight the need for MCP-specific vulnerability detection techniques while reaffirming the value of traditional analysis and refactoring practices.

Foundation models are predominantly trained in an unsupervised or self-supervised manner on highly diverse and large-scale datasets, making them broadly applicable to various downstream tasks. In this work, we investigate for the first time whether such models are suitable for the specific domain of face recognition. We further propose and demonstrate the adaptation of these models for face recognition across different levels of data availability. Extensive experiments are conducted on multiple foundation models and datasets of varying scales for training and fine-tuning, with evaluation on a wide range of benchmarks. Our results indicate that, despite their versatility, pre-trained foundation models underperform in face recognition compared to similar architectures trained specifically for this task. However, fine-tuning foundation models yields promising results, often surpassing models trained from scratch when training data is limited. Even with access to large-scale face recognition training datasets, fine-tuned foundation models perform comparably to models trained from scratch, but with lower training computational costs and without relying on the assumption of extensive data availability. Our analysis also explores bias in face recognition, with slightly higher bias observed in some settings when using foundation models.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

Continuous normalizing flows (CNFs) are an attractive generative modeling technique, but they have been held back by limitations in their simulation-based maximum likelihood training. We introduce the generalized conditional flow matching (CFM) technique, a family of simulation-free training objectives for CNFs. CFM features a stable regression objective like that used to train the stochastic flow in diffusion models but enjoys the efficient inference of deterministic flow models. In contrast to both diffusion models and prior CNF training algorithms, CFM does not require the source distribution to be Gaussian or require evaluation of its density. A variant of our objective is optimal transport CFM (OT-CFM), which creates simpler flows that are more stable to train and lead to faster inference, as evaluated in our experiments. Furthermore, we show that when the true OT plan is available, our OT-CFM method approximates dynamic OT. Training CNFs with CFM improves results on a variety of conditional and unconditional generation tasks, such as inferring single cell dynamics, unsupervised image translation, and Schr\"odinger bridge inference.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

In machine learning, generalization against distribution shifts -- where deployment conditions diverge from the training scenarios -- is crucial, particularly in fields like climate modeling, biomedicine, and autonomous driving. The emergence of foundation models, distinguished by their extensive pretraining and task versatility, has led to an increased interest in their adaptability to distribution shifts. GPT-4V(ision) acts as the most advanced publicly accessible multimodal foundation model, with extensive applications across various domains, including anomaly detection, video understanding, image generation, and medical diagnosis. However, its robustness against data distributions remains largely underexplored. Addressing this gap, this study rigorously evaluates GPT-4V's adaptability and generalization capabilities in dynamic environments, benchmarking against prominent models like CLIP and LLaVA. We delve into GPT-4V's zero-shot generalization across 13 diverse datasets spanning natural, medical, and molecular domains. We further investigate its adaptability to controlled data perturbations and examine the efficacy of in-context learning as a tool to enhance its adaptation. Our findings delineate GPT-4V's capability boundaries in distribution shifts, shedding light on its strengths and limitations across various scenarios. Importantly, this investigation contributes to our understanding of how AI foundation models generalize to distribution shifts, offering pivotal insights into their adaptability and robustness. Code is publicly available at https://github.com/jameszhou-gl/gpt-4v-distribution-shift.

The simulation of the metabolism in mammalian cells becomes a severe problem if spatial distributions must be taken into account. Especially the cytoplasm has a very complex geometric structure which cannot be handled by standard discretization techniques. In the present paper we propose a homogenization technique for computing effective diffusion constants. This is accomplished by using a two-step strategy. The first step consists of an analytic homogenization from the smallest to an intermediate scale. The homogenization error is estimated by comparing the analytic diffusion constant with a numerical estimate obtained by using real cell geometries. The second step consists of a random homogenization. Since no analytical solution is known to this homogenization problem, a numerical approximation algorithm is proposed. Although rather expensive this algorithm provides a reasonable estimate of the homogenized diffusion constant.

Foundation models (FMs), large deep learning models pre-trained on vast, unlabeled datasets, exhibit powerful capabilities in understanding complex patterns and generating sophisticated outputs. However, they often struggle to adapt to specific tasks. Reinforcement learning (RL), which allows agents to learn through interaction and feedback, offers a compelling solution. Integrating RL with FMs enables these models to achieve desired outcomes and excel at particular tasks. Additionally, RL can be enhanced by leveraging the reasoning and generalization capabilities of FMs. This synergy is revolutionizing various fields, including robotics. FMs, rich in knowledge and generalization, provide robots with valuable information, while RL facilitates learning and adaptation through real-world interactions. This survey paper comprehensively explores this exciting intersection, examining how these paradigms can be integrated to advance robotic intelligence. We analyze the use of foundation models as action planners, the development of robotics-specific foundation models, and the mutual benefits of combining FMs with RL. Furthermore, we present a taxonomy of integration approaches, including large language models, vision-language models, diffusion models, and transformer-based RL models. We also explore how RL can utilize world representations learned from FMs to enhance robotic task execution. Our survey aims to synthesize current research and highlight key challenges in robotic reasoning and control, particularly in the context of integrating FMs and RL--two rapidly evolving technologies. By doing so, we seek to spark future research and emphasize critical areas that require further investigation to enhance robotics. We provide an updated collection of papers based on our taxonomy, accessible on our open-source project website at: https://github.com/clmoro/Robotics-RL-FMs-Integration.

Foundation models encompass an extensive knowledge base and offer remarkable transferability. However, this knowledge becomes outdated or insufficient over time. The challenge lies in continuously updating foundation models to accommodate novel information while retaining their original capabilities. Leveraging the fact that foundation models have initial knowledge on various tasks and domains, we propose a novel approach that, instead of updating all parameters equally, localizes the updates to a sparse set of parameters relevant to the task being learned. We strike a balance between efficiency and new task performance, while maintaining the transferability and generalizability of foundation models. We extensively evaluate our method on foundational vision-language models with a diverse spectrum of continual learning tasks. Our method achieves improvements on the accuracy of the newly learned tasks up to 7% while preserving the pretraining knowledge with a negligible decrease of 0.9% on a representative control set accuracy.

The successes of foundation models such as ChatGPT and AlphaFold have spurred significant interest in building similar models for electronic medical records (EMRs) to improve patient care and hospital operations. However, recent hype has obscured critical gaps in our understanding of these models' capabilities. We review over 80 foundation models trained on non-imaging EMR data (i.e. clinical text and/or structured data) and create a taxonomy delineating their architectures, training data, and potential use cases. We find that most models are trained on small, narrowly-scoped clinical datasets (e.g. MIMIC-III) or broad, public biomedical corpora (e.g. PubMed) and are evaluated on tasks that do not provide meaningful insights on their usefulness to health systems. In light of these findings, we propose an improved evaluation framework for measuring the benefits of clinical foundation models that is more closely grounded to metrics that matter in healthcare.

Foundation models (FM), such as large language models (LLMs), which are large-scale machine learning (ML) models, have demonstrated remarkable adaptability in various downstream software engineering (SE) tasks, such as code completion, code understanding, and software development. As a result, FM leaderboards, especially those hosted on cloud platforms, have become essential tools for SE teams to compare and select the best third-party FMs for their specific products and purposes. However, the lack of standardized guidelines for FM evaluation and comparison threatens the transparency of FM leaderboards and limits stakeholders' ability to perform effective FM selection. As a first step towards addressing this challenge, our research focuses on understanding how these FM leaderboards operate in real-world scenarios ("leaderboard operations") and identifying potential leaderboard pitfalls and areas for improvement ("leaderboard smells"). In this regard, we perform a multivocal literature review to collect up to 721 FM leaderboards, after which we examine their documentation and engage in direct communication with leaderboard operators to understand their workflow patterns. Using card sorting and negotiated agreement, we identify 5 unique workflow patterns and develop a domain model that outlines the essential components and their interaction within FM leaderboards. We then identify 8 unique types of leaderboard smells in LBOps. By mitigating these smells, SE teams can improve transparency, accountability, and collaboration in current LBOps practices, fostering a more robust and responsible ecosystem for FM comparison and selection.

A handful of visual foundation models (VFMs) have recently emerged as the backbones for numerous downstream tasks. VFMs like CLIP, DINOv2, SAM are trained with distinct objectives, exhibiting unique characteristics for various downstream tasks. We find that despite their conceptual differences, these models can be effectively merged into a unified model through multi-teacher distillation. We name this approach AM-RADIO (Agglomerative Model -- Reduce All Domains Into One). This integrative approach not only surpasses the performance of individual teacher models but also amalgamates their distinctive features, such as zero-shot vision-language comprehension, detailed pixel-level understanding, and open vocabulary segmentation capabilities. In pursuit of the most hardware-efficient backbone, we evaluated numerous architectures in our multi-teacher distillation pipeline using the same training recipe. This led to the development of a novel architecture (E-RADIO) that exceeds the performance of its predecessors and is at least 7x faster than the teacher models. Our comprehensive benchmarking process covers downstream tasks including ImageNet classification, ADE20k semantic segmentation, COCO object detection and LLaVa-1.5 framework. Code: https://github.com/NVlabs/RADIO

Vision foundation models (VFMs) trained on large-scale image datasets provide high-quality features that have significantly advanced 2D visual recognition. However, their potential in 3D vision remains largely untapped, despite the common availability of 2D images alongside 3D point cloud datasets. While significant research has been dedicated to 2D-3D fusion, recent state-of-the-art 3D methods predominantly focus on 3D data, leaving the integration of VFMs into 3D models underexplored. In this work, we challenge this trend by introducing DITR, a simple yet effective approach that extracts 2D foundation model features, projects them to 3D, and finally injects them into a 3D point cloud segmentation model. DITR achieves state-of-the-art results on both indoor and outdoor 3D semantic segmentation benchmarks. To enable the use of VFMs even when images are unavailable during inference, we further propose to distill 2D foundation models into a 3D backbone as a pretraining task. By initializing the 3D backbone with knowledge distilled from 2D VFMs, we create a strong basis for downstream 3D segmentation tasks, ultimately boosting performance across various datasets.

Developing accurate models for chemical reactors is often challenging due to the complexity of reaction kinetics and process dynamics. Traditional approaches require retraining models for each new system, limiting generalizability and efficiency. In this work, we take a step toward foundation models for chemical reactor modeling by introducing a neural network framework that generalizes across diverse reactor types and rapidly adapts to new chemical processes. Our approach leverages meta-learning to pretrain the model on a broad set of reactor dynamics, enabling efficient adaptation to unseen reactions with minimal data. To further enhance generalizability, we incorporate physics-informed fine-tuning, ensuring physically consistent adaptation to new reactor conditions. Our framework is evaluated across three integer-order fundamental reactor types - continuous stirred tank reactors, batch reactors, and plug flow reactors - demonstrating superior few-shot adaptation compared to conventional data-driven, physics-informed, and transfer learning approaches. By combining meta-learning with physics-informed adaptation, this work lays the foundation for a generalizable modeling framework, advancing the development of foundation models for chemical engineering applications. Source code is available at https://github.com/killingbear999/chemical-reactor-foundation-model.

Foundation models (FMs) have transformed natural language processing, but their success has not yet translated to time series forecasting. Existing time series foundation models (TSFMs), often based on transformer variants, struggle with generalization across varying context and target lengths, lack adaptability to different sampling rates, and are computationally inefficient. We introduce FlowState, a novel TSFM architecture that addresses these challenges through two key innovations: a state space model (SSM) based encoder and a functional basis decoder. This design enables continuous-time modeling and dynamic time-scale adjustment, allowing FlowState to inherently generalize across all possible temporal resolutions, and dynamically adjust the forecasting horizons. In contrast to other state-of-the-art TSFMs, which require training data across all possible sampling rates to memorize patterns at each scale, FlowState inherently adapts its internal dynamics to the input scale, enabling smaller models, reduced data requirements, and improved efficiency. We further propose an efficient pretraining strategy that improves robustness and accelerates training. Despite being the smallest model, FlowState outperforms all other models and is state-of-the-art for the GIFT-ZS and the Chronos-ZS benchmarks. Ablation studies confirm the effectiveness of its components, and we demonstrate its unique ability to adapt online to varying input sampling rates.

Cutting-edge research in Artificial Intelligence (AI) requires considerable resources, including Graphics Processing Units (GPUs), data, and human resources. In this paper, we evaluate of the relationship between these resources and the scientific advancement of foundation models (FM). We reviewed 6517 FM papers published between 2022 to 2024, and surveyed 229 first-authors to the impact of computing resources on scientific output. We find that increased computing is correlated with national funding allocations and citations, but our findings don't observe the strong correlations with research environment (academic or industrial), domain, or study methodology. We advise that individuals and institutions focus on creating shared and affordable computing opportunities to lower the entry barrier for under-resourced researchers. These steps can help expand participation in FM research, foster diversity of ideas and contributors, and sustain innovation and progress in AI. The data will be available at: https://mit-calc.csail.mit.edu/

The advanced function-calling capabilities of foundation models open up new possibilities for deploying agents to perform complex API tasks. However, managing large amounts of data and interacting with numerous APIs makes function calling hardware-intensive and costly, especially on edge devices. Current Large Language Models (LLMs) struggle with function calling at the edge because they cannot handle complex inputs or manage multiple tools effectively. This results in low task-completion accuracy, increased delays, and higher power consumption. In this work, we introduce Less-is-More, a novel fine-tuning-free function-calling scheme for dynamic tool selection. Our approach is based on the key insight that selectively reducing the number of tools available to LLMs significantly improves their function-calling performance, execution time, and power efficiency on edge devices. Experimental results with state-of-the-art LLMs on edge hardware show agentic success rate improvements, with execution time reduced by up to 70% and power consumption by up to 40%.

The foundation model has recently garnered significant attention due to its potential to revolutionize the field of visual representation learning in a self-supervised manner. While most foundation models are tailored to effectively process RGB images for various visual tasks, there is a noticeable gap in research focused on spectral data, which offers valuable information for scene understanding, especially in remote sensing (RS) applications. To fill this gap, we created for the first time a universal RS foundation model, named SpectralGPT, which is purpose-built to handle spectral RS images using a novel 3D generative pretrained transformer (GPT). Compared to existing foundation models, SpectralGPT 1) accommodates input images with varying sizes, resolutions, time series, and regions in a progressive training fashion, enabling full utilization of extensive RS big data; 2) leverages 3D token generation for spatial-spectral coupling; 3) captures spectrally sequential patterns via multi-target reconstruction; 4) trains on one million spectral RS images, yielding models with over 600 million parameters. Our evaluation highlights significant performance improvements with pretrained SpectralGPT models, signifying substantial potential in advancing spectral RS big data applications within the field of geoscience across four downstream tasks: single/multi-label scene classification, semantic segmentation, and change detection.

The emergent phenomena of large foundation models have revolutionized natural language processing. However, evaluating these models presents significant challenges due to their size, capabilities, and deployment across diverse applications. Existing literature often focuses on individual aspects, such as benchmark performance or specific tasks, but fails to provide a cohesive process that integrates the nuances of diverse use cases with broader ethical and operational considerations. This work focuses on three key aspects: (1) Formalizing the Evaluation Process by providing a structured framework tailored to specific use-case contexts, (2) Offering Actionable Tools and Frameworks such as checklists and templates to ensure thorough, reproducible, and practical evaluations, and (3) Surveying Recent Work with a targeted review of advancements in LLM evaluation, emphasizing real-world applications.

Foundation models, such as large language models (LLMs), have been widely recognised as transformative AI technologies due to their capabilities to understand and generate content, including plans with reasoning capabilities. Foundation model based agents derive their autonomy from the capabilities of foundation models, which enable them to autonomously break down a given goal into a set of manageable tasks and orchestrate task execution to meet the goal. Despite the huge efforts put into building foundation model based agents, the architecture design of the agents has not yet been systematically explored. Also, while there are significant benefits of using agents for planning and execution, there are serious considerations regarding responsible AI related software quality attributes, such as security and accountability. Therefore, this paper presents a pattern-oriented reference architecture that serves as guidance when designing foundation model based agents. We evaluate the completeness and utility of the proposed reference architecture by mapping it to the architecture of two real-world agents.

With the growing complexity and dynamics of the mobile communication networks, accurately predicting key system parameters, such as channel state information (CSI), user location, and network traffic, has become essential for a wide range of physical (PHY)-layer and medium access control (MAC)-layer tasks. Although traditional deep learning (DL)-based methods have been widely applied to such prediction tasks, they often struggle to generalize across different scenarios and tasks. In response, we propose a unified foundation model for multi-task prediction in wireless networks that supports diverse prediction intervals. The proposed model enforces univariate decomposition to unify heterogeneous tasks, encodes granularity for interval awareness, and uses a causal Transformer backbone for accurate predictions. Additionally, we introduce a patch masking strategy during training to support arbitrary input lengths. After trained on large-scale datasets, the proposed foundation model demonstrates strong generalization to unseen scenarios and achieves zero-shot performance on new tasks that surpass traditional full-shot baselines.

As foundation models grow rapidly in capability and deployment, evaluating their scientific understanding becomes increasingly critical. Existing science benchmarks have made progress towards broad **Range**, wide **Reach**, and high **Rigor**, yet they often face two major challenges: **data leakage risks** that compromise benchmarking validity, and **evaluation inefficiency** due to large-scale testing. To address these issues, we introduce the **Ever-Evolving Science Exam (EESE)**, a dynamic benchmark designed to reliably assess scientific capabilities in foundation models. Our approach consists of two components: 1) a non-public **EESE-Pool** with over 100K expertly constructed science instances (question-answer pairs) across 5 disciplines and 500+ subfields, built through a multi-stage pipeline ensuring **Range**, **Reach**, and **Rigor**, 2) a periodically updated 500-instance subset **EESE**, sampled and validated to enable leakage-resilient, low-overhead evaluations. Experiments on 32 open- and closed-source models demonstrate that EESE effectively differentiates the strengths and weaknesses of models in scientific fields and cognitive dimensions. Overall, EESE provides a robust, scalable, and forward-compatible solution for science benchmark design, offering a realistic measure of how well foundation models handle science questions. The project page is at: https://github.com/aiben-ch/EESE.

The advent of foundation models (FMs) as an emerging suite of AI techniques has struck a wave of opportunities in computational healthcare. The interactive nature of these models, guided by pre-training data and human instructions, has ignited a data-centric AI paradigm that emphasizes better data characterization, quality, and scale. In healthcare AI, obtaining and processing high-quality clinical data records has been a longstanding challenge, ranging from data quantity, annotation, patient privacy, and ethics. In this survey, we investigate a wide range of data-centric approaches in the FM era (from model pre-training to inference) towards improving the healthcare workflow. We discuss key perspectives in AI security, assessment, and alignment with human values. Finally, we offer a promising outlook of FM-based analytics to enhance the performance of patient outcome and clinical workflow in the evolving landscape of healthcare and medicine. We provide an up-to-date list of healthcare-related foundation models and datasets at https://github.com/Yunkun-Zhang/Data-Centric-FM-Healthcare .

The success of large pretrained models in natural language processing (NLP) and computer vision (CV) has opened new avenues for constructing foundation models for time series forecasting (TSF). Traditional TSF foundation models rely heavily on numerical data fitting. In contrast, the human brain is inherently skilled at processing visual information, prefer predicting future trends by observing visualized sequences. From a biomimetic perspective, utilizing models to directly process numerical sequences might not be the most effective route to achieving Artificial General Intelligence (AGI). This paper proposes ViTime, a novel Visual Intelligence-based foundation model for TSF. ViTime overcomes the limitations of numerical time series data fitting by utilizing visual data processing paradigms and employs a innovative data synthesis method during training, called Real Time Series (RealTS). Experiments on a diverse set of previously unseen forecasting datasets demonstrate that ViTime achieves state-of-the-art zero-shot performance, even surpassing the best individually trained supervised models in some situations. These findings suggest that visual intelligence can significantly enhance time series analysis and forecasting, paving the way for more advanced and versatile models in the field. The code for our framework is accessible at https://github.com/IkeYang/ViTime.

Large foundation models are typically trained on data from multiple domains, with the data mixture--the proportion of each domain used--playing a critical role in model performance. The standard approach to selecting this mixture relies on trial and error, which becomes impractical for large-scale pretraining. We propose a systematic method to determine the optimal data mixture for any target domain using scaling laws. Our approach accurately predicts the loss of a model of size N trained with D tokens and a specific domain weight vector h. We validate the universality of these scaling laws by demonstrating their predictive power in three distinct and large-scale settings: large language model (LLM), native multimodal model (NMM), and large vision models (LVM) pretraining. We further show that these scaling laws can extrapolate to new data mixtures and across scales: their parameters can be accurately estimated using a few small-scale training runs, and used to estimate the performance at larger scales and unseen domain weights. The scaling laws allow to derive the optimal domain weights for any target domain under a given training budget (N,D), providing a principled alternative to costly trial-and-error methods.

Transformer-based foundation models have emerged as a dominant paradigm in time series analysis, offering unprecedented capabilities in tasks such as forecasting, anomaly detection, classification, trend analysis and many more time series analytical tasks. This survey provides a comprehensive overview of the current state of the art pre-trained foundation models, introducing a novel taxonomy to categorize them across several dimensions. Specifically, we classify models by their architecture design, distinguishing between those leveraging patch-based representations and those operating directly on raw sequences. The taxonomy further includes whether the models provide probabilistic or deterministic predictions, and whether they are designed to work with univariate time series or can handle multivariate time series out of the box. Additionally, the taxonomy encompasses model scale and complexity, highlighting differences between lightweight architectures and large-scale foundation models. A unique aspect of this survey is its categorization by the type of objective function employed during training phase. By synthesizing these perspectives, this survey serves as a resource for researchers and practitioners, providing insights into current trends and identifying promising directions for future research in transformer-based time series modeling.

Featurizing microscopy images for use in biological research remains a significant challenge, especially for large-scale experiments spanning millions of images. This work explores the scaling properties of weakly supervised classifiers and self-supervised masked autoencoders (MAEs) when training with increasingly larger model backbones and microscopy datasets. Our results show that ViT-based MAEs outperform weakly supervised classifiers on a variety of tasks, achieving as much as a 11.5% relative improvement when recalling known biological relationships curated from public databases. Additionally, we develop a new channel-agnostic MAE architecture (CA-MAE) that allows for inputting images of different numbers and orders of channels at inference time. We demonstrate that CA-MAEs effectively generalize by inferring and evaluating on a microscopy image dataset (JUMP-CP) generated under different experimental conditions with a different channel structure than our pretraining data (RPI-93M). Our findings motivate continued research into scaling self-supervised learning on microscopy data in order to create powerful foundation models of cellular biology that have the potential to catalyze advancements in drug discovery and beyond.

Predicting the intermediate trajectories between an initial and target distribution is a central problem in generative modeling. Existing approaches, such as flow matching and Schr\"odinger Bridge Matching, effectively learn mappings between two distributions by modeling a single stochastic path. However, these methods are inherently limited to unimodal transitions and cannot capture branched or divergent evolution from a common origin to multiple distinct outcomes. To address this, we introduce Branched Schr\"odinger Bridge Matching (BranchSBM), a novel framework that learns branched Schr\"odinger bridges. BranchSBM parameterizes multiple time-dependent velocity fields and growth processes, enabling the representation of population-level divergence into multiple terminal distributions. We show that BranchSBM is not only more expressive but also essential for tasks involving multi-path surface navigation, modeling cell fate bifurcations from homogeneous progenitor states, and simulating diverging cellular responses to perturbations.

Cell migration in vivo is often guided by chemical signals. Such chemotaxis, such as performed by immune cells migrating to a wound site, is complicated by the complex geometry inside living tissues. In this study, we extend our theoretical model of branched-cell migration on a network by introducing chemokine sources to explore the cellular response. The model predicts a speed-accuracy tradeoff, whereby slow cells are significantly more accurate and able to follow efficiently a weak chemoattractant signal. We then compare the model's predictions with experimental observations of neutrophils migrating to the site of laser-inflicted wound in a zebrafish larva fin, and migrating in-vitro inside a regular lattice of pillars. We find that the model captures the details of the sub-cellular response to the chemokine gradient, as well as the large-scale migration response. This comparison suggests that the neutrophils behave as fast cells, compromising their chemotaxis accuracy, which explains the functionality of these immune cells.

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Foundation models (FMs) achieve strong performance across diverse tasks with task-specific fine-tuning, yet full parameter fine-tuning is often computationally prohibitive for large models. Parameter-efficient fine-tuning (PEFT) methods like Low-Rank Adaptation (LoRA) reduce this cost by introducing low-rank matrices for tuning fewer parameters. While LoRA allows for efficient fine-tuning, it requires significant data for adaptation, making Federated Learning (FL) an appealing solution due to its privacy-preserving collaborative framework. However, combining LoRA with FL introduces two key challenges: the Server-Side LoRA Aggregation Bias, where server-side averaging of LoRA matrices diverges from the ideal global update, and the Client-Side LoRA Initialization Drift, emphasizing the need for consistent initialization across rounds. Existing approaches address these challenges individually, limiting their effectiveness. We propose LoRA-FAIR, a novel method that tackles both issues by introducing a correction term on the server while keeping the original LoRA modules, enhancing aggregation efficiency and accuracy. LoRA-FAIR maintains computational and communication efficiency, yielding superior performance over state-of-the-art methods. Experimental results on ViT and MLP-Mixer models across large-scale datasets demonstrate that LoRA-FAIR consistently achieves performance improvements in FL settings.

Recently, pre-trained foundation models have enabled significant advancements in multiple fields. In molecular machine learning, however, where datasets are often hand-curated, and hence typically small, the lack of datasets with labeled features, and codebases to manage those datasets, has hindered the development of foundation models. In this work, we present seven novel datasets categorized by size into three distinct categories: ToyMix, LargeMix and UltraLarge. These datasets push the boundaries in both the scale and the diversity of supervised labels for molecular learning. They cover nearly 100 million molecules and over 3000 sparsely defined tasks, totaling more than 13 billion individual labels of both quantum and biological nature. In comparison, our datasets contain 300 times more data points than the widely used OGB-LSC PCQM4Mv2 dataset, and 13 times more than the quantum-only QM1B dataset. In addition, to support the development of foundational models based on our proposed datasets, we present the Graphium graph machine learning library which simplifies the process of building and training molecular machine learning models for multi-task and multi-level molecular datasets. Finally, we present a range of baseline results as a starting point of multi-task and multi-level training on these datasets. Empirically, we observe that performance on low-resource biological datasets show improvement by also training on large amounts of quantum data. This indicates that there may be potential in multi-task and multi-level training of a foundation model and fine-tuning it to resource-constrained downstream tasks.

Computer vision foundation models, such as DINO or OpenCLIP, are trained in a self-supervised manner on large image datasets. Analogously, substantial evidence suggests that the human visual system (HVS) is influenced by the statistical distribution of colors and patterns in the natural world, characteristics also present in the training data of foundation models. The question we address in this paper is whether foundation models trained on natural images mimic some of the low-level characteristics of the human visual system, such as contrast detection, contrast masking, and contrast constancy. Specifically, we designed a protocol comprising nine test types to evaluate the image encoders of 45 foundation and generative models. Our results indicate that some foundation models (e.g., DINO, DINOv2, and OpenCLIP), share some of the characteristics of human vision, but other models show little resemblance. Foundation models tend to show smaller sensitivity to low contrast and rather irregular responses to contrast across frequencies. The foundation models show the best agreement with human data in terms of contrast masking. Our findings suggest that human vision and computer vision may take both similar and different paths when learning to interpret images of the real world. Overall, while differences remain, foundation models trained on vision tasks start to align with low-level human vision, with DINOv2 showing the closest resemblance.

Many have observed that the development and deployment of generative machine learning (ML) and artificial intelligence (AI) models follow a distinctive pattern in which pre-trained models are adapted and fine-tuned for specific downstream tasks. However, there is limited empirical work that examines the structure of these interactions. This paper analyzes 1.86 million models on Hugging Face, a leading peer production platform for model development. Our study of model family trees -- networks that connect fine-tuned models to their base or parent -- reveals sprawling fine-tuning lineages that vary widely in size and structure. Using an evolutionary biology lens to study ML models, we use model metadata and model cards to measure the genetic similarity and mutation of traits over model families. We find that models tend to exhibit a family resemblance, meaning their genetic markers and traits exhibit more overlap when they belong to the same model family. However, these similarities depart in certain ways from standard models of asexual reproduction, because mutations are fast and directed, such that two `sibling' models tend to exhibit more similarity than parent/child pairs. Further analysis of the directional drifts of these mutations reveals qualitative insights about the open machine learning ecosystem: Licenses counter-intuitively drift from restrictive, commercial licenses towards permissive or copyleft licenses, often in violation of upstream license's terms; models evolve from multi-lingual compatibility towards english-only compatibility; and model cards reduce in length and standardize by turning, more often, to templates and automatically generated text. Overall, this work takes a step toward an empirically grounded understanding of model fine-tuning and suggests that ecological models and methods can yield novel scientific insights.

Foundation models trained on vast amounts of data have demonstrated remarkable reasoning and generation capabilities in the domains of text, images, audio and video. Our goal at Roblox is to build such a foundation model for 3D intelligence, a model that can support developers in producing all aspects of a Roblox experience, from generating 3D objects and scenes to rigging characters for animation to producing programmatic scripts describing object behaviors. We discuss three key design requirements for such a 3D foundation model and then present our first step towards building such a model. We expect that 3D geometric shapes will be a core data type and describe our solution for 3D shape tokenizer. We show how our tokenization scheme can be used in applications for text-to-shape generation, shape-to-text generation and text-to-scene generation. We demonstrate how these applications can collaborate with existing large language models (LLMs) to perform scene analysis and reasoning. We conclude with a discussion outlining our path to building a fully unified foundation model for 3D intelligence.

General-purpose foundation models have become increasingly important in the field of artificial intelligence. While self-supervised learning (SSL) and Masked Image Modeling (MIM) have led to promising results in building such foundation models for remote sensing, these models primarily learn low-level features, require annotated data for fine-tuning, and not applicable for retrieval and zero-shot applications due to the lack of language understanding. In response to these limitations, we propose RemoteCLIP, the first vision-language foundation model for remote sensing that aims to learn robust visual features with rich semantics, as well as aligned text embeddings for seamless downstream application. To address the scarcity of pre-training data, we leverage data scaling, converting heterogeneous annotations based on Box-to-Caption (B2C) and Mask-to-Box (M2B) conversion, and further incorporating UAV imagery, resulting a 12xlarger pretraining dataset. RemoteCLIP can be applied to a variety of downstream tasks, including zero-shot image classification, linear probing, k-NN classification, few-shot classification, image-text retrieval, and object counting. Evaluations on 16 datasets, including a newly introduced RemoteCount benchmark to test the object counting ability, show that RemoteCLIP consistently outperforms baseline foundation models across different model scales. Impressively, RemoteCLIP outperform previous SoTA by 9.14% mean recall on RSICD dataset and by 8.92% on RSICD dataset. For zero-shot classification, our RemoteCLIP outperform CLIP baseline by up to 6.39% average accuracy on 12 downstream datasets.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

The transformer architecture has revolutionized bioinformatics and driven progress in the understanding and prediction of the properties of biomolecules. Almost all research on large-scale biosequence transformers has focused on one domain at a time (single-omic), usually nucleotides or peptides. These models have seen incredible success in downstream tasks in each domain and have achieved particularly noteworthy breakthroughs in sequences of peptides and structural modeling. However, these single-omic models are naturally incapable of modeling multi-omic tasks, one of the most biologically critical being nucleotide-peptide interactions. We present our work training the first multi-omic nucleotide-peptide foundation models. We show that these multi-omic models (MOMs) can learn joint representations between various single-omic distributions that are emergently consistent with the Central Dogma of molecular biology, despite only being trained on unlabeled biosequences. We further demonstrate that MOMs can be fine-tuned to achieve state-of-the-art results on peptide-nucleotide interaction tasks, namely predicting the change in Gibbs free energy ({\Delta}G) of the binding interaction between a given oligonucleotide and peptide, as well as the effect on this binding interaction due to mutations in the oligonucleotide sequence ({\Delta}{\Delta}G). Remarkably, we show that multi-omic biosequence transformers emergently learn useful structural information without any prior structural training, allowing us to predict which peptide residues are most involved in the peptide-nucleotide binding interaction. Lastly, we provide evidence that multi-omic biosequence models are non-inferior to foundation models trained on single-omics distributions, suggesting a more generalized or foundational approach to building these models.

Automated visual understanding of our diverse and open world demands computer vision models to generalize well with minimal customization for specific tasks, similar to human vision. Computer vision foundation models, which are trained on diverse, large-scale dataset and can be adapted to a wide range of downstream tasks, are critical for this mission to solve real-world computer vision applications. While existing vision foundation models such as CLIP, ALIGN, and Wu Dao 2.0 focus mainly on mapping images and textual representations to a cross-modal shared representation, we introduce a new computer vision foundation model, Florence, to expand the representations from coarse (scene) to fine (object), from static (images) to dynamic (videos), and from RGB to multiple modalities (caption, depth). By incorporating universal visual-language representations from Web-scale image-text data, our Florence model can be easily adapted for various computer vision tasks, such as classification, retrieval, object detection, VQA, image caption, video retrieval and action recognition. Moreover, Florence demonstrates outstanding performance in many types of transfer learning: fully sampled fine-tuning, linear probing, few-shot transfer and zero-shot transfer for novel images and objects. All of these properties are critical for our vision foundation model to serve general purpose vision tasks. Florence achieves new state-of-the-art results in majority of 44 representative benchmarks, e.g., ImageNet-1K zero-shot classification with top-1 accuracy of 83.74 and the top-5 accuracy of 97.18, 62.4 mAP on COCO fine tuning, 80.36 on VQA, and 87.8 on Kinetics-600.

Recent advances in large language models (LLMs) and multi-agent systems have demonstrated remarkable capabilities in complex problem-solving tasks such as deep research, vibe coding, and mathematical reasoning. However, most existing multi-agent systems are built upon manual prompt/workflow engineering with sophisticated agent frameworks, making them computationally inefficient, less capable, and can not benefit from data-centric learning. In this work, we introduce Chain-of-Agents (CoA), a novel paradigm of LLM reasoning that enables native end-to-end complex problem-solving in the same way as a multi-agent system (i.e., multi-turn problem solving with multiple tools and multiple agents) within one model. In chain-of-agents problem-solving, the model dynamically activates different tool agents and role-playing agents to simulate multi-agent collaboration in an end-to-end fashion. To elicit end-to-end chain-of-agents problem-solving abilities in LLMs, we introduce a multi-agent distillation framework to distill state-of-the-art multi-agent systems into chain-of-agents trajectories for agentic supervised fine-tuning. We then use agentic reinforcement learning on verifiable agentic tasks to further improve the models' capabilities on chain-of-agents problem solving. We call the resulting models Agent Foundation Models (AFMs). Our empirical studies demonstrate that AFM establishes new state-of-the-art performance across diverse benchmarks in both web agent and code agent settings. We make the entire research, including the model weights, code for training and evaluation, and the training data, fully open-sourced, which offers a solid starting point for future research on agent models and agentic RL.

Many methods have been proposed for removing batch effects and aligning single-cell RNA (scRNA) datasets. However, performance is typically evaluated based on multiple parameters and few datasets, creating challenges in assessing which method is best for aligning data at scale. Here, we introduce the K-Neighbors Intersection (KNI) score, a single score that both penalizes batch effects and measures accuracy at cross-dataset cell-type label prediction alongside carefully curated small (scMARK) and large (scREF) benchmarks comprising 11 and 46 human scRNA studies respectively, where we have standardized author labels. Using the KNI score, we evaluate and optimize approaches for cross-dataset single-cell RNA integration. We introduce Batch Adversarial single-cell Variational Inference (BA-scVI), as a new variant of scVI that uses adversarial training to penalize batch-effects in the encoder and decoder, and show this approach outperforms other methods. In the resulting aligned space, we find that the granularity of cell-type groupings is conserved, supporting the notion that whole-organism cell-type maps can be created by a single model without loss of information.

We introduce IntFold, a controllable foundation model for both general and specialized biomolecular structure prediction. IntFold demonstrates predictive accuracy comparable to the state-of-the-art AlphaFold3, while utilizing a superior customized attention kernel. Beyond standard structure prediction, IntFold can be adapted to predict allosteric states, constrained structures, and binding affinity through the use of individual adapters. Furthermore, we introduce a novel confidence head to estimate docking quality, offering a more nuanced assessment for challenging targets such as antibody-antigen complexes. Finally, we share insights gained during the training process of this computationally intensive model.

Foundation models have triggered a paradigm shift in computer vision and are increasingly being adopted in remote sensing, particularly for multispectral imagery. Yet, their potential in hyperspectral imaging (HSI) remains untapped due to the absence of comprehensive and globally representative hyperspectral datasets. To close this gap, we introduce SpectralEarth, a large-scale multi-temporal dataset designed to pretrain hyperspectral foundation models leveraging data from the Environmental Mapping and Analysis Program (EnMAP). SpectralEarth comprises 538,974 image patches covering 415,153 unique locations from more than 11,636 globally distributed EnMAP scenes spanning two years of archive. Additionally, 17.5% of these locations include multiple timestamps, enabling multi-temporal HSI analysis. Utilizing state-of-the-art self-supervised learning (SSL) algorithms, we pretrain a series of foundation models on SpectralEarth. We integrate a spectral adapter into classical vision backbones to accommodate the unique characteristics of HSI. In tandem, we construct four downstream datasets for land-cover and crop-type mapping, providing benchmarks for model evaluation. Experimental results support the versatility of our models, showcasing their generalizability across different tasks and sensors. We also highlight computational efficiency during model fine-tuning. The dataset, models, and source code will be made publicly available.

Artificial Intelligence (AI) Foundation models (FMs), pre-trained on massive unlabelled datasets, have the potential to drastically change AI applications in ocean science, where labelled data are often sparse and expensive to collect. In this work, we describe a new foundation model using the Prithvi-EO Vision Transformer architecture which has been pre-trained to reconstruct data from the Sentinel-3 Ocean and Land Colour Instrument (OLCI). We evaluate the model by fine-tuning on two downstream marine earth observation tasks. We first assess model performance compared to current baseline models used to quantify chlorophyll concentration. We then evaluate the FMs ability to refine remote sensing-based estimates of ocean primary production. Our results demonstrate the utility of self-trained FMs for marine monitoring, in particular for making use of small amounts of high quality labelled data and in capturing detailed spatial patterns of ocean colour whilst matching point observations. We conclude that this new generation of geospatial AI models has the potential to provide more robust, data-driven insights into ocean ecosystems and their role in global climate processes.

The rapid development and application of foundation models have revolutionized the field of artificial intelligence. Large diffusion models have gained significant attention for their ability to generate photorealistic images and support various tasks. On-device deployment of these models provides benefits such as lower server costs, offline functionality, and improved user privacy. However, common large diffusion models have over 1 billion parameters and pose challenges due to restricted computational and memory resources on devices. We present a series of implementation optimizations for large diffusion models that achieve the fastest reported inference latency to-date (under 12 seconds for Stable Diffusion 1.4 without int8 quantization on Samsung S23 Ultra for a 512x512 image with 20 iterations) on GPU-equipped mobile devices. These enhancements broaden the applicability of generative AI and improve the overall user experience across a wide range of devices.

Artificial intelligence (AI) has demonstrated significant potential in ECG analysis and cardiovascular disease assessment. Recently, foundation models have played a remarkable role in advancing medical AI. The development of an ECG foundation model holds the promise of elevating AI-ECG research to new heights. However, building such a model faces several challenges, including insufficient database sample sizes and inadequate generalization across multiple domains. Additionally, there is a notable performance gap between single-lead and multi-lead ECG analyses. We introduced an ECG Foundation Model (ECGFounder), a general-purpose model that leverages real-world ECG annotations from cardiology experts to broaden the diagnostic capabilities of ECG analysis. ECGFounder was trained on over 10 million ECGs with 150 label categories from the Harvard-Emory ECG Database, enabling comprehensive cardiovascular disease diagnosis through ECG analysis. The model is designed to be both an effective out-of-the-box solution, and a to be fine-tunable for downstream tasks, maximizing usability. Importantly, we extended its application to lower rank ECGs, and arbitrary single-lead ECGs in particular. ECGFounder is applicable to supporting various downstream tasks in mobile monitoring scenarios. Experimental results demonstrate that ECGFounder achieves expert-level performance on internal validation sets, with AUROC exceeding 0.95 for eighty diagnoses. It also shows strong classification performance and generalization across various diagnoses on external validation sets. When fine-tuned, ECGFounder outperforms baseline models in demographic analysis, clinical event detection, and cross-modality cardiac rhythm diagnosis. The trained model and data will be publicly released upon publication through the bdsp.io. Our code is available at https://github.com/bdsp-core/ECGFounder