Daily Papers

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.

Agentic AI is rapidly advancing in healthcare and biomedical research. However, in medical image analysis, their performance and adoption remain limited due to the lack of a robust ecosystem, insufficient toolsets, and the absence of real-time interactive expert feedback. Here we present "TissueLab", a co-evolving agentic AI system that allows researchers to ask direct questions, automatically plan and generate explainable workflows, and conduct real-time analyses where experts can visualize intermediate results and refine them. TissueLab integrates tool factories across pathology, radiology, and spatial omics domains. By standardizing inputs, outputs, and capabilities of diverse tools, the system determines when and how to invoke them to address research and clinical questions. Across diverse tasks with clinically meaningful quantifications that inform staging, prognosis, and treatment planning, TissueLab achieves state-of-the-art performance compared with end-to-end vision-language models (VLMs) and other agentic AI systems such as GPT-5. Moreover, TissueLab continuously learns from clinicians, evolving toward improved classifiers and more effective decision strategies. With active learning, it delivers accurate results in unseen disease contexts within minutes, without requiring massive datasets or prolonged retraining. Released as a sustainable open-source ecosystem, TissueLab aims to accelerate computational research and translational adoption in medical imaging while establishing a foundation for the next generation of medical AI.

Spatial transcriptomics (ST) provides spatially resolved measurements of gene expression, enabling characterization of the molecular landscape of human tissue beyond histological assessment as well as localized readouts that can be aligned with morphology. Concurrently, the success of multimodal foundation models that integrate vision with complementary modalities suggests that morphomolecular coupling between local expression and morphology can be systematically used to improve histological representations themselves. We introduce Spatial Expression-Aligned Learning (SEAL), a vision-omics self-supervised learning framework that infuses localized molecular information into pathology vision encoders. Rather than training new encoders from scratch, SEAL is designed as a parameter-efficient vision-omics finetuning method that can be flexibly applied to widely used pathology foundation models. We instantiate SEAL by training on over 700,000 paired gene expression spot-tissue region examples spanning tumor and normal samples from 14 organs. Tested across 38 slide-level and 15 patch-level downstream tasks, SEAL provides a drop-in replacement for pathology foundation models that consistently improves performance over widely used vision-only and ST prediction baselines on slide-level molecular status, pathway activity, and treatment response prediction, as well as patch-level gene expression prediction tasks. Additionally, SEAL encoders exhibit robust domain generalization on out-of-distribution evaluations and enable new cross-modal capabilities such as gene-to-image retrieval. Our work proposes a general framework for ST-guided finetuning of pathology foundation models, showing that augmenting existing models with localized molecular supervision is an effective and practical step for improving visual representations and expanding their cross-modal utility.

Spatial transcriptomics (ST) enables interrogating the molecular composition of tissue with ever-increasing resolution, depth, and sensitivity. However, costs, rapidly evolving technology, and lack of standards have constrained computational methods in ST to narrow tasks and small cohorts. In addition, the underlying tissue morphology as reflected by H&E-stained whole slide images (WSIs) encodes rich information often overlooked in ST studies. Here, we introduce HEST-1k, a collection of 1,108 spatial transcriptomic profiles, each linked to a WSI and metadata. HEST-1k was assembled using HEST-Library from 131 public and internal cohorts encompassing 25 organs, two species (Homo Sapiens and Mus Musculus), and 320 cancer samples from 25 cancer types. HEST-1k processing enabled the identification of 1.5 million expression--morphology pairs and 60 million nuclei. HEST-1k is tested on three use cases: (1) benchmarking foundation models for histopathology (HEST-Benchmark), (2) biomarker identification, and (3) multimodal representation learning. HEST-1k, HEST-Library, and HEST-Benchmark can be freely accessed via https://github.com/mahmoodlab/hest.

Spatial transcriptomics (ST) provides high-resolution pathological images and whole-transcriptomic expression profiles at individual spots across whole-slide scales. This setting makes it an ideal data source to develop multimodal foundation models. Although recent studies attempted to fine-tune visual encoders with trainable gene encoders based on spot-level, the absence of a wider slide perspective and spatial intrinsic relationships limits their ability to capture ST-specific insights effectively. Here, we introduce ST-Align, the first foundation model designed for ST that deeply aligns image-gene pairs by incorporating spatial context, effectively bridging pathological imaging with genomic features. We design a novel pretraining framework with a three-target alignment strategy for ST-Align, enabling (1) multi-scale alignment across image-gene pairs, capturing both spot- and niche-level contexts for a comprehensive perspective, and (2) cross-level alignment of multimodal insights, connecting localized cellular characteristics and broader tissue architecture. Additionally, ST-Align employs specialized encoders tailored to distinct ST contexts, followed by an Attention-Based Fusion Network (ABFN) for enhanced multimodal fusion, effectively merging domain-shared knowledge with ST-specific insights from both pathological and genomic data. We pre-trained ST-Align on 1.3 million spot-niche pairs and evaluated its performance through two downstream tasks across six datasets, demonstrating superior zero-shot and few-shot capabilities. ST-Align highlights the potential for reducing the cost of ST and providing valuable insights into the distinction of critical compositions within human tissue.

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.

Spatial proteomics enables single-cell-resolution characterization of protein expression within tissue architecture, playing a critical role in understanding tumor microenvironments and guiding precision medicine. However, current analysis workflows remain fragmented, requiring expert manual orchestration of heterogeneous tools and limiting research scalability and reproducibility. We present SP-Mind, the first autonomous AI agent designed to unify the spatial proteomics analysis pipeline, from raw multiplexed tissue imaging to downstream phenotype discovery. Equipped with expert-curated biological analysis skills and specialized computational tools, SP-Mind converts natural-language queries into end-to-end analytical workflows without task-specific fine-tuning. To rigorously evaluate its capabilities, we introduce SP-Bench, a comprehensive benchmark spanning diverse tissue types, comprising 102 tasks across 18 distinct categories. Through extensive evaluation on SP-Bench and established downstream tasks, SP-Mind achieves state-of-the-art performance compared to existing open-source biomedical agent baselines.

Spatial proteomics technologies have transformed our understanding of complex tissue architectures by enabling simultaneous analysis of multiple molecular markers and their spatial organization. The high dimensionality of these data, varying marker combinations across experiments and heterogeneous study designs pose unique challenges for computational analysis. Here, we present Virtual Tissues (VirTues), a foundation model framework for biological tissues that operates across the molecular, cellular and tissue scale. VirTues introduces innovations in transformer architecture design, including a novel tokenization scheme that captures both spatial and marker dimensions, and attention mechanisms that scale to high-dimensional multiplex data while maintaining interpretability. Trained on diverse cancer and non-cancer tissue datasets, VirTues demonstrates strong generalization capabilities without task-specific fine-tuning, enabling cross-study analysis and novel marker integration. As a generalist model, VirTues outperforms existing approaches across clinical diagnostics, biological discovery and patient case retrieval tasks, while providing insights into tissue function and disease mechanisms.

Foundation models have begun to transform image analysis by acting as pretrained generalist backbones that can be adapted to many tasks even when post-training data are limited, yet their impact on spatial proteomics, imaging that maps proteins at single-cell resolution, remains limited. Here, we introduce KRONOS, a foundation model built for spatial proteomics. KRONOS was trained in a self-supervised manner on over 47 million image patches covering 175 protein markers, 16 tissue types, and 8 fluorescence-based imaging platforms. We introduce key architectural adaptations to address the high-dimensional, multi-channel, and heterogeneous nature of multiplex imaging. We demonstrate that KRONOS learns biologically meaningful representations across multiple scales, ranging from cellular and microenvironment to tissue levels, enabling it to address diverse downstream tasks, including cell phenotyping, region classification, and patient stratification. Evaluated across 11 independent cohorts, KRONOS achieves state-of-the-art performance across cell phenotyping, treatment response prediction, and retrieval tasks, and is highly data-efficient. KRONOS also introduces the paradigm of segmentation-free patch-level processing for efficient and scalable spatial proteomics analysis, allowing cross-institutional comparisons, and as an image reverse search engine for spatial patterns. Together, these results position KRONOS as a flexible and scalable tool for spatial proteomics. The model is publicly accessible at https://github.com/mahmoodlab/KRONOS.

Integrating molecular, morphological, and clinical data is essential for basic and translational biomedical research, yet systematic frameworks for jointly modeling these modalities remain limited. Here we present Haiku, a tri-modal contrastive learning model trained on multiplexed immunofluorescence (mIF). It comprises 26.7 million spatial proteomics patches from 3,218 tissue sections across 1,606 patients spanning 11 organ types, with matched hematoxylin and eosin (H&E) histology and clinical metadata aligned in a shared embedding space. Haiku enables three-way cross-modal retrieval, improves downstream classification and clinical prediction tasks over unimodal baselines, and supports zero-shot biomarker inference through fusion retrieval conditioned on clinical metadata-only text descriptions. Across tasks, Haiku outperforms competing approaches, achieving cross-modal retrieval (Recall@50 up to 0.611 versus near-zero baseline), survival prediction (C-index 0.737, +7.91% relative improvement), and zero-shot biomarker inference (mean Pearson correlation 0.718 across 52 biomarkers). Furthermore, we introduce a counterfactual prediction framework in which modifying only clinical metadata while fixing tissue morphology surfaces niche-specific molecular shifts associated with breast cancer stage progression and lung cancer survival outcomes. In a lung adenocarcinoma case study, the counterfactual analysis recovers niche-specific shifts characterized by increased CD8 and granzyme B, reduced PD-L1, and decreased Ki67, broadly consistent with patterns reported for favorable outcomes. We present these counterfactual results as exploratory, hypothesis-generating signals rather than mechanistic claims. These capabilities demonstrate that tri-modal alignment via Haiku enables integrative analysis of spatial biology, bridging molecular measurements with clinical context for biological exploration.

Spatial intelligence remains a persistent challenge for Multimodal Large Language Models (MLLMs), as it requires coherent spatial scene representations beyond basic object recognition. Existing methods typically build such representations through textual reasoning or 3D reconstruction. However, they often falter during multi-step reasoning, particularly when required to dynamically re-anchor evidence to the specific camera-, object-, or direction-centric reference frames demanded by complex queries. To address this, we propose OmniView-Space, a framework designed to maintain spatial consistency through multimodal egocentric evidence. Our approach consists of three core components: (1) Multi-Perspective Spatial Mapping (MPSM), which re-anchors reconstructed geometry into a query-aligned visual cognitive map and a textual spatial graph; (2) Tool-Guided Egocentric Reasoning, an interleaved policy trained to actively select the ego anchor required by the query and request the corresponding MPSM evidence; and (3) Cognitive-Map Distillation, which uses MPSM-generated trajectories and ego-frame rewards to train the model to reason with self-generated cognitive maps. Experiments on single- and multi-image spatial reasoning benchmarks show that OmniView-Space achieves state-of-the-art performance. Furthermore, the distilled model maintains this performance while reducing reliance on external geometry pipelines.

The molecular characterization of tumor samples by multiple omics data sets of different types or modalities (e.g. gene expression, mutation, CpG methylation) has become an invaluable source of information for assessing the expected performance of individual drugs and their combinations. Merging the relevant information from the omics data modalities provides the statistical basis for determining suitable therapies for specific cancer patients. Different data modalities may each have their specific structures that need to be taken into account during inference. In this paper, we assume that each omics data modality has a low-rank structure with only few relevant features that affect the prediction and we propose to use a composite local nuclear norm penalization for learning drug sensitivity. Numerical results show that the composite low-rank structure can improve the prediction performance compared to using a global low-rank approach or elastic net regression.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

Cancer progression arises from interactions across multiple biological layers, especially beyond morphological and across molecular layers that remain invisible to image-only models. To capture this broader biological landscape, we present EXAONE Path 2.5, a pathology foundation model that jointly models histologic, genomic, epigenetic and transcriptomic modalities, producing an integrated patient representation that reflects tumor biology more comprehensively. Our approach incorporates three key components: (1) multimodal SigLIP loss enabling all-pairwise contrastive learning across heterogeneous modalities, (2) a fragment-aware rotary positional encoding (F-RoPE) module that preserves spatial structure and tissue-fragment topology in WSI, and (3) domain-specialized internal foundation models for both WSI and RNA-seq to provide biologically grounded embeddings for robust multimodal alignment. We evaluate EXAONE Path 2.5 against six leading pathology foundation models across two complementary benchmarks: an internal real-world clinical dataset and the Patho-Bench benchmark covering 80 tasks. Our framework demonstrates high data and parameter efficiency, achieving on-par performance with state-of-the-art foundation models on Patho-Bench while exhibiting the highest adaptability in the internal clinical setting. These results highlight the value of biologically informed multimodal design and underscore the potential of integrated genotype-to-phenotype modeling for next-generation precision oncology.

Understanding how cellular morphology, gene expression, and spatial context jointly shape tissue function is a central challenge in biology. Image-based spatial transcriptomics technologies now provide high-resolution measurements of cell images and gene expression profiles, but existing methods typically analyze these modalities in isolation or at limited resolution. We address the problem by introducing SPATIA, a multi-level generative and predictive model that learns unified, spatially aware representations by fusing morphology, gene expression, and spatial context from the cell to the tissue level. SPATIA also incorporates a spatially conditioned generative framework with confidence-aware OT reweighting and morphology-profile alignment for modeling target-state morphology distributions. Specifically, we propose a confidence-aware flow matching objective that reweights weak optimal-transport pairs based on uncertainty. We further apply morphology-profile alignment to encourage biologically meaningful image generation, enabling the modeling of microenvironment-dependent phenotypic transitions. We assembled a multi-scale dataset consisting of 25.9 million cell-gene pairs across 17 tissues. We benchmark SPATIA against 18 models across 12 tasks, spanning categories such as phenotype generation, annotation, clustering, gene imputation, and cross-modal prediction. SPATIA achieves improved performance over state-of-the-art models, improving generative fidelity by 8% and predictive accuracy by up to 3%.

Humans perceive and understand real-world spaces through a stream of visual observations. Therefore, the ability to streamingly maintain and update spatial evidence from potentially unbounded video streams is essential for spatial intelligence. The core challenge is not simply longer context windows but how spatial information is selected, organized, and retained over time. In this paper, we propose Spatial-TTT towards streaming visual-based spatial intelligence with test-time training (TTT), which adapts a subset of parameters (fast weights) to capture and organize spatial evidence over long-horizon scene videos. Specifically, we design a hybrid architecture and adopt large-chunk updates parallel with sliding-window attention for efficient spatial video processing. To further promote spatial awareness, we introduce a spatial-predictive mechanism applied to TTT layers with 3D spatiotemporal convolution, which encourages the model to capture geometric correspondence and temporal continuity across frames. Beyond architecture design, we construct a dataset with dense 3D spatial descriptions, which guides the model to update its fast weights to memorize and organize global 3D spatial signals in a structured manner. Extensive experiments demonstrate that Spatial-TTT improves long-horizon spatial understanding and achieves state-of-the-art performance on video spatial benchmarks. Project page: https://liuff19.github.io/Spatial-TTT.

Advancements in high-throughput technologies have led to a shift from traditional hypothesis-driven methodologies to data-driven approaches. Multi-omics refers to the integrative analysis of data derived from multiple 'omes', such as genomics, proteomics, transcriptomics, metabolomics, and microbiomics. This approach enables a comprehensive understanding of biological systems by capturing different layers of biological information. Deep learning methods are increasingly utilized to integrate multi-omics data, offering insights into molecular interactions and enhancing research into complex diseases. However, these models, with their numerous interconnected layers and nonlinear relationships, often function as black boxes, lacking transparency in decision-making processes. To overcome this challenge, explainable artificial intelligence (xAI) methods are crucial for creating transparent models that allow clinicians to interpret and work with complex data more effectively. This review explores how xAI can improve the interpretability of deep learning models in multi-omics research, highlighting its potential to provide clinicians with clear insights, thereby facilitating the effective application of such models in clinical settings.

Spatial computing is a technological advancement that facilitates the seamless integration of devices into the physical environment, resulting in a more natural and intuitive digital world user experience. Spatial computing has the potential to become a significant advancement in the field of computing. From GPS and location-based services to healthcare, spatial computing technologies have influenced and improved our interactions with the digital world. The use of spatial computing in creating interactive digital environments has become increasingly popular and effective. This is explained by its increasing significance among researchers and industrial organisations, which motivated us to conduct this review. This review provides a detailed overview of spatial computing, including its enabling technologies and its impact on various applications. Projects related to spatial computing are also discussed. In this review, we also explored the potential challenges and limitations of spatial computing. Furthermore, we discuss potential solutions and future directions. Overall, this paper aims to provide a comprehensive understanding of spatial computing, its enabling technologies, their impact on various applications, emerging challenges, and potential solutions.

Spatial understanding is a fundamental cornerstone of human-level intelligence. Nonetheless, current research predominantly focuses on domain-specific data production, leaving a critical void: the absence of a principled, open-source engine capable of fully unleashing the potential of high-quality spatial data. To bridge this gap, we elucidate the design principles of a robust data generation system and introduce OpenSpatial -- an open-source data engine engineered for high quality, extensive scalability, broad task diversity, and optimized efficiency. OpenSpatial adopts 3D bounding boxes as the fundamental primitive to construct a comprehensive data hierarchy across five foundational tasks: Spatial Measurement (SM), Spatial Relationship (SR), Camera Perception (CP), Multi-view Consistency (MC), and Scene-Aware Reasoning (SAR). Leveraging this scalable infrastructure, we curate OpenSpatial-3M, a large-scale dataset comprising 3 million high-fidelity samples. Extensive evaluations demonstrate that versatile models trained on our dataset achieve state-of-the-art performance across a wide spectrum of spatial reasoning benchmarks. Notably, the best-performing model exhibits a substantial average improvement of 19 percent, relatively. Furthermore, we provide a systematic analysis of how data attributes influence spatial perception. By open-sourcing both the engine and the 3M-scale dataset, we provide a robust foundation to accelerate future research in spatial intelligence.

Spatial intelligence is essential for agents to move from static semantic understanding toward interacting with the physical world. Many spatial tasks are grounded in continuous visual scenes, where locations, regions, and paths are more naturally expressed by pointing, marking, or drawing than by reporting precise coordinates or discrete textual symbols. Yet existing spatial reasoning benchmarks usually require coordinates, options, or text, creating an answer-interface mismatch for image-generation models. This makes it difficult to evaluate image-generation models under the same task semantics as text-output VLMs, despite their ability to externalize spatial judgments directly in pixel space. We propose ProVisE (Protocolized Visual Evaluation), a benchmark-agnostic framework that elicits protocol-constrained visual answers from image-generation models and parses them into structured predictions compatible with original metrics. ProVisE also includes an Agentic builder that constructs and validates task-specific protocols for new benchmarks. We further introduce SpatialGen-Bench, a curated diagnostic benchmark of 470 samples across 14 spatial subtasks, four capability levels, and diverse answer forms. We evaluate representative text-output VLMs and image-generation models in a unified setting and validate Agentic protocol construction on six external spatial benchmarks. Results show that image-generation models are competitive when spatial answers can be externalized directly in pixel space, while text-output VLMs retain a clear advantage in compositional spatial reasoning. These findings reveal complementary strengths of pixel-space expression and text-based reasoning and establish a metric-compatible testbed for studying spatial cognition in image-generation models.

Spatial reasoning is a crucial component of both biological and artificial intelligence. In this work, we present a comprehensive study of the capability of current state-of-the-art large language models (LLMs) on spatial reasoning. To support our study, we created and contribute a novel Spatial Reasoning Characterization (SpaRC) framework and Spatial Reasoning Paths (SpaRP) datasets, to enable an in-depth understanding of the spatial relations and compositions as well as the usefulness of spatial reasoning chains. We found that all the state-of-the-art LLMs do not perform well on the datasets -- their performances are consistently low across different setups. The spatial reasoning capability improves substantially as model sizes scale up. Finetuning both large language models (e.g., Llama-2-70B) and smaller ones (e.g., Llama-2-13B) can significantly improve their F1-scores by 7--32 absolute points. We also found that the top proprietary LLMs still significantly outperform their open-source counterparts in topological spatial understanding and reasoning.

Spatial intelligence is a critical frontier for Multimodal Large Language Models (MLLMs), empowering them to comprehend the physical world. Drawing inspiration from human perception mechanisms, existing studies attempt to construct a coherent spatial understanding via grid-based cognitive maps from multi-frame visual inputs. However, current grid-based map methods rely on discretized raster representations, which limit the model's ability in fine-grained spatial reasoning. To overcome this limitation, we propose Video2Layout, a framework for reconstructing metric-grounded spatial layouts from video. The framework employs continuous object boundary coordinates to quantify inter-object physical distances and object size. This empowers the model with quantitative spatial computation capabilities, effectively alleviating the inherent ambiguity when describing spatial relationships in natural language. Specifically, our method comprises two core stages. First, in supervised fine-tuning stage, we construct a high-quality dataset from the AI2THOR simulator, which enables the model to learn the mapping from visual inputs to precise boundary coordinates. Subsequently, a reinforcement fine-tuning stage further enhances the model's real-world generalization capabilities. To systematically evaluate the correlation between cognitive map accuracy and image quantity, as well as how the quantity of image inputs affects spatial reasoning accuracy, we introduce QVS-Bench, a diagnostic benchmark designed to analyze the relevant mechanisms. Evaluated on QVS-Bench and mainstream spatial reasoning benchmarks, our model, V2LO-7B achieves an average improvement of 4.92% over the model trained on grid maps, validating the superiority of our method. Our code is available at https://github.com/ybrrraway/Video2Layout.

Spatial confounding poses a significant challenge in scientific studies involving spatial data, where unobserved spatial variables can influence both treatment and outcome, possibly leading to spurious associations. To address this problem, we introduce SpaCE: The Spatial Confounding Environment, the first toolkit to provide realistic benchmark datasets and tools for systematically evaluating causal inference methods designed to alleviate spatial confounding. Each dataset includes training data, true counterfactuals, a spatial graph with coordinates, and smoothness and confounding scores characterizing the effect of a missing spatial confounder. It also includes realistic semi-synthetic outcomes and counterfactuals, generated using state-of-the-art machine learning ensembles, following best practices for causal inference benchmarks. The datasets cover real treatment and covariates from diverse domains, including climate, health and social sciences. SpaCE facilitates an automated end-to-end pipeline, simplifying data loading, experimental setup, and evaluating machine learning and causal inference models. The SpaCE project provides several dozens of datasets of diverse sizes and spatial complexity. It is publicly available as a Python package, encouraging community feedback and contributions.

Inferring spatial transcriptomics (ST) from histology enables scalable histogenomic profiling, yet current methods are largely restricted to single-tissue models. This fragmentation fails to leverage biological principles shared across cancer types and hinders application to data-scarce scenarios. While pan-cancer training offers a solution, the resulting heterogeneity challenges monolithic architectures. To bridge this gap, we introduce MoLF (Mixture-of-Latent-Flow), a generative model for pan-cancer histogenomic prediction. MoLF leverages a conditional Flow Matching objective to map noise to the gene latent manifold, parameterized by a Mixture-of-Experts (MoE) velocity field. By dynamically routing inputs to specialized sub-networks, this architecture effectively decouples the optimization of diverse tissue patterns. Our experiments demonstrate that MoLF establishes a new state-of-the-art, consistently outperforming both specialized and foundation model baselines on pan-cancer benchmarks. Furthermore, MoLF exhibits zero-shot generalization to cross-species data, suggesting it captures fundamental, conserved histo-molecular mechanisms.

Conventional tissue image analysis software provides foundational capabilities for cellular analysis, including segmentation, basic morphological feature extraction, and spatial organization analysis. However, these tools often require manual intervention and are not well integrated with code-driven automation, limiting efficiency and scalability for complex spatial tissue studies. In addition, they offer limited flexibility for custom analyses, as they typically support only a fixed set of pre-implemented spatial cellular features. To address these limitations, we propose CodeCytos, a coding-based reasoning agent framework that enables dynamic, programmable interaction with spatial molecular imaging data to improve automation and customization. CodeCytos is designed to streamline the exploration of custom spatial cellular features and adapt to diverse research needs. We demonstrate its utility through case studies on four expert-curated datasets from distinct tissue types: frontal cortex, non-small-cell lung cancer, pancreas, and tonsil. We evaluate CodeCytos under a realistic minimal prompt setting, where bioscientists pose simple questions without task-specific instructions or contextual information about spatial cellular analysis, and benchmark multiple LLM backbones with strong coding capabilities. We further show that incorporating tailored, domain-agnostic few-shot in-context coding-reasoning examples (randomly sampled demonstrations outside the spatial analysis domain) can substantially improve performance without requiring costly, expert-crafted in-domain demonstrations. Overall, CodeCytos outperforms baseline approaches, highlighting the potential of code-action agents to assist with custom feature exploration in spatial molecular imaging and to accelerate biomarker discovery.

The rapid advancement of multimodal large language models (LLMs) has opened new frontiers in artificial intelligence, enabling the integration of diverse large-scale data types such as text, images, and spatial information. In this paper, we explore the potential of multimodal LLMs (MLLM) for geospatial artificial intelligence (GeoAI), a field that leverages spatial data to address challenges in domains including Geospatial Semantics, Health Geography, Urban Geography, Urban Perception, and Remote Sensing. We propose a MLLM (OmniGeo) tailored to geospatial applications, capable of processing and analyzing heterogeneous data sources, including satellite imagery, geospatial metadata, and textual descriptions. By combining the strengths of natural language understanding and spatial reasoning, our model enhances the ability of instruction following and the accuracy of GeoAI systems. Results demonstrate that our model outperforms task-specific models and existing LLMs on diverse geospatial tasks, effectively addressing the multimodality nature while achieving competitive results on the zero-shot geospatial tasks. Our code will be released after publication.

Spatial transcriptomics enables simultaneous measurement of gene expression and tissue morphology, offering unprecedented insights into cellular organization and disease mechanisms. However, the field lacks comprehensive benchmarks for evaluating multimodal learning methods that leverage both histology images and gene expression data. Here, we present HESCAPE, a large-scale benchmark for cross-modal contrastive pretraining in spatial transcriptomics, built on a curated pan-organ dataset spanning 6 different gene panels and 54 donors. We systematically evaluated state-of-the-art image and gene expression encoders across multiple pretraining strategies and assessed their effectiveness on two downstream tasks: gene mutation classification and gene expression prediction. Our benchmark demonstrates that gene expression encoders are the primary determinant of strong representational alignment, and that gene models pretrained on spatial transcriptomics data outperform both those trained without spatial data and simple baseline approaches. However, downstream task evaluation reveals a striking contradiction: while contrastive pretraining consistently improves gene mutation classification performance, it degrades direct gene expression prediction compared to baseline encoders trained without cross-modal objectives. We identify batch effects as a key factor that interferes with effective cross-modal alignment. Our findings highlight the critical need for batch-robust multimodal learning approaches in spatial transcriptomics. To accelerate progress in this direction, we release HESCAPE, providing standardized datasets, evaluation protocols, and benchmarking tools for the community

Predicting spatial gene expression from H&E histology offers a scalable and clinically accessible alternative to sequencing, but realizing clinical impact requires models that generalize across cancer types and capture biologically coherent signals. Prior work is often limited to per-cancer settings and variance-based evaluation, leaving functional relevance underexplored. We introduce HistoPrism, an efficient transformer-based architecture for pan-cancer prediction of gene expression from histology. To evaluate biological meaning, we introduce a pathway-level benchmark, shifting assessment from isolated gene-level variance to coherent functional pathways. HistoPrism not only surpasses prior state-of-the-art models on highly variable genes , but also more importantly, achieves substantial gains on pathway-level prediction, demonstrating its ability to recover biologically coherent transcriptomic patterns. With strong pan-cancer generalization and improved efficiency, HistoPrism establishes a new standard for clinically relevant transcriptomic modeling from routinely available histology.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through integration of all available multi-omics data is an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a deep neural network trained on multi-omics data across 33 cancer types. SeNMo is efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival using pan-cancer data involving 33 cancer sites from Genomics Data Commons (GDC). The training data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. We evaluated the model's performance in predicting overall survival using concordance index (C-Index). SeNMo performed consistently well in training regime, with the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo proved to be a mini-foundation model for multi-omics oncology data because it demonstrated robust performance, and adaptability not only across molecular data types but also on the classification task of predicting the primary cancer type of patients. SeNMo can be further scaled to any cancer site and molecular data type. We believe SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and patient-centric cancer care.

Spatial intelligence (SI) represents a cognitive ability encompassing the visualization, manipulation, and reasoning about spatial relationships, underpinning disciplines from neuroscience to robotics. We introduce SITE, a benchmark dataset towards SI Thorough Evaluation in a standardized format of multi-choice visual question-answering, designed to assess large vision-language models' spatial intelligence across diverse visual modalities (single-image, multi-image, and video) and SI factors (figural to environmental scales, spatial visualization and orientation, intrinsic and extrinsic, static and dynamic). Our approach to curating the benchmark combines a bottom-up survey about 31 existing datasets and a top-down strategy drawing upon three classification systems in cognitive science, which prompt us to design two novel types of tasks about view-taking and dynamic scenes. Extensive experiments reveal that leading models fall behind human experts especially in spatial orientation, a fundamental SI factor. Moreover, we demonstrate a positive correlation between a model's spatial reasoning proficiency and its performance on an embodied AI task.

Visual spatial intelligence is critical for medical image interpretation, yet remains largely unexplored in Multimodal Large Language Models (MLLMs) for 3D imaging. This gap persists due to a systemic lack of datasets featuring structured 3D spatial annotations beyond basic labels. In this study, we introduce an agentic pipeline that autonomously synthesizes spatial visual question-answering (VQA) data by orchestrating computational tools such as volume and distance calculators with multi-agent collaboration and expert radiologist validation. We present SpatialMed, the first comprehensive benchmark for evaluating 3D spatial intelligence in medical MLLMs, comprising nearly 10K question-answer pairs across multiple organs and tumor types. Our evaluations on 14 state-of-the-art MLLMs and extensive analyses reveal that current models lack robust spatial reasoning capabilities for medical imaging.

Answering real-world geospatial questions--such as finding restaurants along a travel route or amenities near a landmark--requires reasoning over both geographic relationships and semantic user intent. However, existing large language models (LLMs) lack spatial computing capabilities and access to up-to-date, ubiquitous real-world geospatial data, while traditional geospatial systems fall short in interpreting natural language. To bridge this gap, we introduce Spatial-RAG, a Retrieval-Augmented Generation (RAG) framework designed for geospatial question answering. Spatial-RAG integrates structured spatial databases with LLMs via a hybrid spatial retriever that combines sparse spatial filtering and dense semantic matching. It formulates the answering process as a multi-objective optimization over spatial and semantic relevance, identifying Pareto-optimal candidates and dynamically selecting the best response based on user intent. Experiments across multiple tourism and map-based QA datasets show that Spatial-RAG significantly improves accuracy, precision, and ranking performance over strong baselines.

This paper introduces the concept of Microscopic Spatial Intelligence (MiSI), the capability to perceive and reason about the spatial relationships of invisible microscopic entities, which is fundamental to scientific discovery. To assess the potential of Vision-Language Models (VLMs) in this domain, we propose a systematic benchmark framework MiSI-Bench. This framework features over 163,000 question-answer pairs and 587,000 images derived from approximately 4,000 molecular structures, covering nine complementary tasks that evaluate abilities ranging from elementary spatial transformations to complex relational identifications. Experimental results reveal that current state-of-the-art VLMs perform significantly below human level on this benchmark. However, a fine-tuned 7B model demonstrates substantial potential, even surpassing humans in spatial transformation tasks, while its poor performance in scientifically-grounded tasks like hydrogen bond recognition underscores the necessity of integrating explicit domain knowledge for progress toward scientific AGI. The datasets are available at https://huggingface.co/datasets/zongzhao/MiSI-bench.

Recent multimodal large language models mainly process audio as monaural signals, thereby discarding the spatial cues contained in spatial audio for sound localization, spatial relation reasoning, and spatial scene understanding. We propose Spatial-Omni, a lightweight method that implements SO-Encoder to inject First-Order Ambisonics (FOA) spatial audio into existing Omni LLMs as an independent modality, without modifying their original audio encoders. SO-Encoder provides spatial tokens with limited additional context cost and improves spatial audio understanding through efficient staged training. To support training and evaluation, we construct SO-Dataset, SO-QA, and SO-Bench from open-source data, real recordings, and simulations, containing 400K FOA spatial audio clips and 2.1M spatial question answering pairs. SO-Bench covers 16 spatial audio understanding subtasks, including basic detection and location estimation, spatial relation understanding, and complex spatial reasoning. Experiments show that Spatial-Omni outperforms existing open-source Large Audio-Language Models (LALMs) and Omni LLM models on spatial audio understanding tasks while retaining a reasonable level of general audio understanding. Code and data are available at https://github.com/dieKarotte/Spatial-Omni.

Spatial relation reasoning is a crucial task for multimodal large language models (MLLMs) to understand the objective world. However, current benchmarks have issues like relying on bounding boxes, ignoring perspective substitutions, or allowing questions to be answered using only the model's prior knowledge without image understanding. To address these issues, we introduce SpatialMQA, a human-annotated spatial relation reasoning benchmark based on COCO2017, which enables MLLMs to focus more on understanding images in the objective world. To ensure data quality, we design a well-tailored annotation procedure, resulting in SpatialMQA consisting of 5,392 samples. Based on this benchmark, a series of closed- and open-source MLLMs are implemented and the results indicate that the current state-of-the-art MLLM achieves only 48.14% accuracy, far below the human-level accuracy of 98.40%. Extensive experimental analyses are also conducted, suggesting the future research directions. The benchmark and codes are available at https://github.com/ziyan-xiaoyu/SpatialMQA.git.

Spatial intelligence is essential for multimodal large language models (MLLMs) operating in the complex physical world. Existing benchmarks, however, probe only single-image relations and thus fail to assess the multi-image spatial reasoning that real-world deployments demand. We introduce MMSI-Bench, a VQA benchmark dedicated to multi-image spatial intelligence. Six 3D-vision researchers spent more than 300 hours meticulously crafting 1,000 challenging, unambiguous multiple-choice questions from over 120,000 images, each paired with carefully designed distractors and a step-by-step reasoning process. We conduct extensive experiments and thoroughly evaluate 34 open-source and proprietary MLLMs, observing a wide gap: the strongest open-source model attains roughly 30% accuracy and OpenAI's o3 reasoning model reaches 40%, while humans score 97%. These results underscore the challenging nature of MMSI-Bench and the substantial headroom for future research. Leveraging the annotated reasoning processes, we also provide an automated error analysis pipeline that diagnoses four dominant failure modes, including (1) grounding errors, (2) overlap-matching and scene-reconstruction errors, (3) situation-transformation reasoning errors, and (4) spatial-logic errors, offering valuable insights for advancing multi-image spatial intelligence. Project page: https://runsenxu.com/projects/MMSI_Bench .

Large Language Models (LLMs) have demonstrated unprecedented capabilities across various natural language processing tasks. Their ability to process and generate viable text and code has made them ubiquitous in many fields, while their deployment as knowledge bases and "reasoning" tools remains an area of ongoing research. In geography, a growing body of literature has been focusing on evaluating LLMs' geographical knowledge and their ability to perform spatial reasoning. However, very little is still known about the internal functioning of these models, especially about how they process geographical information. In this chapter, we establish a novel framework for the study of geospatial mechanistic interpretability - using spatial analysis to reverse engineer how LLMs handle geographical information. Our aim is to advance our understanding of the internal representations that these complex models generate while processing geographical information - what one might call "how LLMs think about geographic information" if such phrasing was not an undue anthropomorphism. We first outline the use of probing in revealing internal structures within LLMs. We then introduce the field of mechanistic interpretability, discussing the superposition hypothesis and the role of sparse autoencoders in disentangling polysemantic internal representations of LLMs into more interpretable, monosemantic features. In our experiments, we use spatial autocorrelation to show how features obtained for placenames display spatial patterns related to their geographic location and can thus be interpreted geospatially, providing insights into how these models process geographical information. We conclude by discussing how our framework can help shape the study and use of foundation models in geography.

As deep learning technology advances and more urban spatial-temporal data accumulates, an increasing number of deep learning models are being proposed to solve urban spatial-temporal prediction problems. However, there are limitations in the existing field, including open-source data being in various formats and difficult to use, few papers making their code and data openly available, and open-source models often using different frameworks and platforms, making comparisons challenging. A standardized framework is urgently needed to implement and evaluate these methods. To address these issues, we propose LibCity, an open-source library that offers researchers a credible experimental tool and a convenient development framework. In this library, we have reproduced 65 spatial-temporal prediction models and collected 55 spatial-temporal datasets, allowing researchers to conduct comprehensive experiments conveniently. By enabling fair model comparisons, designing a unified data storage format, and simplifying the process of developing new models, LibCity is poised to make significant contributions to the spatial-temporal prediction field.

Multimodal large language models (MLLMs) have achieved impressive success in question-answering tasks, yet their capabilities for spatial understanding are less explored. This work investigates a critical question: do existing MLLMs possess 3D spatial perception and understanding abilities? Concretely, we make the following contributions in this paper: (i) we introduce VGBench, a benchmark specifically designed to assess MLLMs for visual geometry perception, e.g., camera pose and motion estimation; (ii) we propose SpatialScore, the most comprehensive and diverse multimodal spatial understanding benchmark to date, integrating VGBench with relevant data from the other 11 existing datasets. This benchmark comprises 28K samples across various spatial understanding tasks, modalities, and QA formats, along with a carefully curated challenging subset, SpatialScore-Hard; (iii) we develop SpatialAgent, a novel multi-agent system incorporating 9 specialized tools for spatial understanding, supporting both Plan-Execute and ReAct reasoning paradigms; (iv) we conduct extensive evaluations to reveal persistent challenges in spatial reasoning while demonstrating the effectiveness of SpatialAgent. We believe SpatialScore will offer valuable insights and serve as a rigorous benchmark for the next evolution of MLLMs.

Spatial audio quality is a highly multifaceted concept, with many interactions between environmental, geometrical, anatomical, psychological, and contextual considerations. Methods for characterization or evaluation of the geometrical components of spatial audio quality, however, remain scarce, despite being perhaps the least subjective aspect of spatial audio quality to quantify. By considering interchannel time and level differences relative to a reference signal, it is possible to construct a signal model to isolate some of the spatial distortion. By using a combination of least-square optimization and heuristics, we propose a signal decomposition method to isolate the spatial error from a processed signal, in terms of interchannel gain leakages and changes in relative delays. This allows the computation of simple energy-ratio metrics, providing objective measures of spatial and non-spatial signal qualities, with minimal assumptions and no dataset dependency. Experiments demonstrate the robustness of the method against common spatial signal degradation introduced by, e.g., audio compression and music source separation. Implementation is available at https://github.com/karnwatcharasupat/spauq.

Hit-like molecular generation with therapeutic potential is essential for target-specific drug discovery. However, the field lacks heterogeneous data and unified frameworks for integrating diverse molecular representations. To bridge this gap, we introduce TextOmics, a pioneering benchmark that establishes one-to-one correspondences between omics expressions and molecular textual descriptions. TextOmics provides a heterogeneous dataset that facilitates molecular generation through representations alignment. Built upon this foundation, we propose ToDi, a generative framework that jointly conditions on omics expressions and molecular textual descriptions to produce biologically relevant, chemically valid, hit-like molecules. ToDi leverages two encoders (OmicsEn and TextEn) to capture multi-level biological and semantic associations, and develops conditional diffusion (DiffGen) for controllable generation. Extensive experiments confirm the effectiveness of TextOmics and demonstrate ToDi outperforms existing state-of-the-art approaches, while also showcasing remarkable potential in zero-shot therapeutic molecular generation. Sources are available at: https://github.com/hala-ToDi.

The pursuit of spatial intelligence fundamentally relies on access to large-scale, fine-grained 3D data. However, existing approaches predominantly construct spatial understanding benchmarks by generating question-answer (QA) pairs from a limited number of manually annotated datasets, rather than systematically annotating new large-scale 3D scenes from raw web data. As a result, their scalability is severely constrained, and model performance is further hindered by domain gaps inherent in these narrowly curated datasets. In this work, we propose Holi-Spatial, the first fully automated, large-scale, spatially-aware multimodal dataset, constructed from raw video inputs without human intervention, using the proposed data curation pipeline. Holi-Spatial supports multi-level spatial supervision, ranging from geometrically accurate 3D Gaussian Splatting (3DGS) reconstructions with rendered depth maps to object-level and relational semantic annotations, together with corresponding spatial Question-Answer (QA) pairs. Following a principled and systematic pipeline, we further construct Holi-Spatial-4M, the first large-scale, high-quality 3D semantic dataset, containing 12K optimized 3DGS scenes, 1.3M 2D masks, 320K 3D bounding boxes, 320K instance captions, 1.2M 3D grounding instances, and 1.2M spatial QA pairs spanning diverse geometric, relational, and semantic reasoning tasks. Holi-Spatial demonstrates exceptional performance in data curation quality, significantly outperforming existing feed-forward and per-scene optimized methods on datasets such as ScanNet, ScanNet++, and DL3DV. Furthermore, fine-tuning Vision-Language Models (VLMs) on spatial reasoning tasks using this dataset has also led to substantial improvements in model performance.

Over the past year, the development of large language models (LLMs) has brought spatial intelligence into focus, with much attention on vision-based embodied intelligence. However, spatial intelligence spans a broader range of disciplines and scales, from navigation and urban planning to remote sensing and earth science. What are the differences and connections between spatial intelligence across these fields? In this paper, we first review human spatial cognition and its implications for spatial intelligence in LLMs. We then examine spatial memory, knowledge representations, and abstract reasoning in LLMs, highlighting their roles and connections. Finally, we analyze spatial intelligence across scales -- from embodied to urban and global levels -- following a framework that progresses from spatial memory and understanding to spatial reasoning and intelligence. Through this survey, we aim to provide insights into interdisciplinary spatial intelligence research and inspire future studies.

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.

Spatial intelligence is essential for multimodal large language models, yet current benchmarks largely assess it only from an understanding perspective. We ask whether modern generative or unified multimodal models also possess generative spatial intelligence (GSI), the ability to respect and manipulate 3D spatial constraints during image generation, and whether such capability can be measured or improved. We introduce GSI-Bench, the first benchmark designed to quantify GSI through spatially grounded image editing. It consists of two complementary components: GSI-Real, a high-quality real-world dataset built via a 3D-prior-guided generation and filtering pipeline, and GSI-Syn, a large-scale synthetic benchmark with controllable spatial operations and fully automated labeling. Together with a unified evaluation protocol, GSI-Bench enables scalable, model-agnostic assessment of spatial compliance and editing fidelity. Experiments show that fine-tuning unified multimodal models on GSI-Syn yields substantial gains on both synthetic and real tasks and, strikingly, also improves downstream spatial understanding. This provides the first clear evidence that generative training can tangibly strengthen spatial reasoning, establishing a new pathway for advancing spatial intelligence in multimodal models.

We present scPilot, the first systematic framework to practice omics-native reasoning: a large language model (LLM) converses in natural language while directly inspecting single-cell RNA-seq data and on-demand bioinformatics tools. scPilot converts core single-cell analyses, i.e., cell-type annotation, developmental-trajectory reconstruction, and transcription-factor targeting, into step-by-step reasoning problems that the model must solve, justify, and, when needed, revise with new evidence. To measure progress, we release scBench, a suite of 9 expertly curated datasets and graders that faithfully evaluate the omics-native reasoning capability of scPilot w.r.t various LLMs. Experiments with o1 show that iterative omics-native reasoning lifts average accuracy by 11% for cell-type annotation and Gemini-2.5-Pro cuts trajectory graph-edit distance by 30% versus one-shot prompting, while generating transparent reasoning traces explain marker gene ambiguity and regulatory logic. By grounding LLMs in raw omics data, scPilot enables auditable, interpretable, and diagnostically informative single-cell analyses. Code, data, and package are available at https://github.com/maitrix-org/scPilot

Multimodal Large Language Models (MLLMs) have achieved remarkable progress in various multimodal tasks. To pursue higher intelligence in space, MLLMs require integrating multiple atomic spatial capabilities to handle complex and dynamic tasks. However, existing benchmarks struggle to comprehensively evaluate the spatial intelligence of common MLLMs from the atomic level to the compositional level. To fill this gap, we present SpaCE-10, a comprehensive benchmark for compositional spatial evaluations. In SpaCE-10, we define 10 atomic spatial capabilities, which are combined to form 8 compositional capabilities. Based on these definitions, we propose a novel hierarchical annotation pipeline to generate high-quality and diverse question-answer (QA) pairs. With over 150+ hours of human expert effort, we obtain over 5k QA pairs for 811 real indoor scenes in SpaCE-10, which covers various evaluation settings like point cloud input and multi-choice QA. We conduct an extensive evaluation of common MLLMs on SpaCE-10 and find that even the most advanced MLLM still lags behind humans by large margins. Through our careful study, we also draw several significant findings that benefit the MLLM community. For example, we reveal that the shortcoming of counting capability greatly limits the compositional spatial capabilities of existing MLLMs. The evaluation code and benchmark datasets are available at https://github.com/Cuzyoung/SpaCE-10.

The rapid progress of Multimodal Large Language Models (MLLMs) has unlocked the potential for enhanced 3D scene understanding and spatial reasoning. A recent line of work explores learning spatial reasoning directly from multi-view images, enabling MLLMs to understand 3D scenes without explicit 3D reconstructions. Nevertheless, key challenges that frequently arise in real-world environments, such as partial visibility, occlusion, and low-overlap conditions that require spatial reasoning from fragmented visual cues, remain under-explored. To address these limitations, we propose a scalable multi-view data generation and annotation pipeline that constructs realistic spatial reasoning QAs, resulting in SpatialMosaic, a comprehensive instruction-tuning dataset featuring 2M QA pairs. We further introduce SpatialMosaic-Bench, a challenging benchmark for evaluating multi-view spatial reasoning under complex and diverse scenarios, consisting of 1M QA pairs across 6 tasks. Our proposed dataset spans both indoor and outdoor scenes, enabling comprehensive evaluation in diverse real-world scenarios. In addition, we introduce a new baseline for multi-view settings, SpatialMosaicVLM, a hybrid framework that integrates 3D reconstruction models as geometry encoders within VLMs for robust spatial reasoning. Extensive experiments demonstrate that our proposed dataset effectively enhances spatial reasoning under challenging multi-view conditions, validating the effectiveness of our data generation pipeline in constructing realistic and challenging QAs. Code and dataset will be available soon.

Spatial intelligence spans a rich suite of abilities, including visualising and transforming shapes, mentally rotating objects, judging relational positions and containment, and estimating numerosity. However, it still remains a critical unresolved challenge for Multimodal Large Language Models (MLLMs).To fill this gap, we propose to treat Euclidean geometry problem-solving as a surrogate task. Specifically, we meticulously constructed a curated multimodal dataset, called Euclid30K, comprising approximately 30K plane and solid geometry problems. To enable the model to acquire and apply Euclidean principles from these geometry problems, we employed Group Relative Policy Optimization (GRPO) to finetune the Qwen2.5VL family and RoboBrain2.0 family, inspiring the models to identify shapes, count, and relate entities, and perform multi-step deductive reasoning using Euclidean principles. Our experiments demonstrate that the resulting models achieve substantial zero-shot gains across four spatial reasoning benchmarks (Super-CLEVR, Omni3DBench, VSI-Bench, and MindCube) without any task-specific adaptations. Notably, after training on the Euclid30K, the mean VSI-Bench accuracy of all evaluated models rose from 34.5% to 40.5%, improving by 5.5 percentage points. Among them, RoboBrain2.0-Euclid-7B achieves 49.6\% accuracy, surpassing the previous state-of-the-art model, Spatial-MLLM.To our knowledge, this is the first systematic study showing that geometry-centric fine-tuning can confer vision-language models with broadly transferable spatial skills. Code and Euclid30K dataset can be found in https://zgca-ai4edu.github.io/Euclids_Gift.

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.

The ability to reason about spatial dynamics is a cornerstone of intelligence, yet current research overlooks the human intent behind spatial changes. To address these limitations, we introduce Teleo-Spatial Intelligence (TSI), a new paradigm that unifies two critical pillars: Physical-Dynamic Reasoning--understanding the physical principles of object interactions--and Intent-Driven Reasoning--inferring the human goals behind these actions. To catalyze research in TSI, we present EscherVerse, consisting of a large-scale, open-world benchmark (Escher-Bench), a dataset (Escher-35k), and models (Escher series). Derived from real-world videos, EscherVerse moves beyond constrained settings to explicitly evaluate an agent's ability to reason about object permanence, state transitions, and trajectory prediction in dynamic, human-centric scenarios. Crucially, it is the first benchmark to systematically assess Intent-Driven Reasoning, challenging models to connect physical events to their underlying human purposes. Our work, including a novel data curation pipeline, provides a foundational resource to advance spatial intelligence from passive scene description toward a holistic, purpose-driven understanding of the world.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

The rapid advancement of high-throughput sequencing has led to large, high-dimensional omics datasets. Deep unsupervised learning architectures, particularly Autoencoders (AEs), are increasingly used for dimensionality reduction and representation learning in this domain. However, AEs are highly sensitive to architectural choices and hyperparameters, and unsupervised optimization typically relies on reconstruction loss, which may be a poor proxy for downstream utility. Exhaustive hyperparameter optimization (HPO) is computationally expensive, leading researchers to frequently rely on suboptimal default configurations. To democratize access to large-scale unsupervised HPO research, we introduce BBOmix, the first open-source tabular benchmark for unsupervised representation learning on real-world biological data. Our benchmark includes 105,000 evaluations across four AE architectures and seven multi-omics modalities from the TCGA and SCHC datasets. We quantify the correlation between reconstruction loss and downstream task performance and provide an extensive evaluation of state-of-the-art single-fidelity, multi-fidelity, and transfer learning HPO methods, establishing a rigorous baseline for future research in unsupervised biological representation learning.

In this paper, we propose HiPoNet, an end-to-end differentiable neural network for regression, classification, and representation learning on high-dimensional point clouds. Our work is motivated by single-cell data which can have very high-dimensionality --exceeding the capabilities of existing methods for point clouds which are mostly tailored for 3D data. Moreover, modern single-cell and spatial experiments now yield entire cohorts of datasets (i.e., one data set for every patient), necessitating models that can process large, high-dimensional point-clouds at scale. Most current approaches build a single nearest-neighbor graph, discarding important geometric and topological information. In contrast, HiPoNet models the point-cloud as a set of higher-order simplicial complexes, with each particular complex being created using a reweighting of features. This method thus generates multiple constructs corresponding to different views of high-dimensional data, which in biology offers the possibility of disentangling distinct cellular processes. It then employs simplicial wavelet transforms to extract multiscale features, capturing both local and global topology from each view. We show that geometric and topological information is preserved in this framework both theoretically and empirically. We showcase the utility of HiPoNet on point-cloud level tasks, involving classification and regression of entire point-clouds in data cohorts. Experimentally, we find that HiPoNet outperforms other point-cloud and graph-based models on single-cell data. We also apply HiPoNet to spatial transcriptomics datasets using spatial coordinates as one of the views. Overall, HiPoNet offers a robust and scalable solution for high-dimensional data analysis.

Recent advancements in Multimodal Large Language Models (MLLMs) have significantly enhanced performance on 2D visual tasks. However, improving their spatial intelligence remains a challenge. Existing 3D MLLMs always rely on additional 3D or 2.5D data to incorporate spatial awareness, restricting their utility in scenarios with only 2D inputs, such as images or videos. In this paper, we present Spatial-MLLM, a novel framework for visual-based spatial reasoning from purely 2D observations. Unlike conventional video MLLMs which rely on CLIP-based visual encoders optimized for semantic understanding, our key insight is to unleash the strong structure prior from the feed-forward visual geometry foundation model. Specifically, we propose a dual-encoder architecture: a pretrained 2D visual encoder to extract semantic features, and a spatial encoder-initialized from the backbone of the visual geometry model-to extract 3D structure features. A connector then integrates both features into unified visual tokens for enhanced spatial understanding. Furthermore, we propose a space-aware frame sampling strategy at inference time, which selects the spatially informative frames of a video sequence, ensuring that even under limited token length, the model focuses on frames critical for spatial reasoning. Beyond architecture improvements, we construct the Spatial-MLLM-120k dataset and train the model on it using supervised fine-tuning and GRPO. Extensive experiments on various real-world datasets demonstrate that our spatial-MLLM achieves state-of-the-art performance in a wide range of visual-based spatial understanding and reasoning tasks. Project page: https://diankun-wu.github.io/Spatial-MLLM/.

We propose SpatialLLM, a novel approach advancing spatial intelligence tasks in complex urban scenes. Unlike previous methods requiring geographic analysis tools or domain expertise, SpatialLLM is a unified language model directly addressing various spatial intelligence tasks without any training, fine-tuning, or expert intervention. The core of SpatialLLM lies in constructing detailed and structured scene descriptions from raw spatial data to prompt pre-trained LLMs for scene-based analysis. Extensive experiments show that, with our designs, pretrained LLMs can accurately perceive spatial distribution information and enable zero-shot execution of advanced spatial intelligence tasks, including urban planning, ecological analysis, traffic management, etc. We argue that multi-field knowledge, context length, and reasoning ability are key factors influencing LLM performances in urban analysis. We hope that SpatialLLM will provide a novel viable perspective for urban intelligent analysis and management. The code and dataset are available at https://github.com/WHU-USI3DV/SpatialLLM.

Significant progress has been made in spatial intelligence, spanning both spatial reconstruction and world exploration. However, the scalability and real-world fidelity of current models remain severely constrained by the scarcity of large-scale, high-quality training data. While several datasets provide camera pose information, they are typically limited in scale, diversity, and annotation richness, particularly for real-world dynamic scenes with ground-truth camera motion. To this end, we collect SpatialVID, a dataset consists of a large corpus of in-the-wild videos with diverse scenes, camera movements and dense 3D annotations such as per-frame camera poses, depth, and motion instructions. Specifically, we collect more than 21,000 hours of raw video, and process them into 2.7 million clips through a hierarchical filtering pipeline, totaling 7,089 hours of dynamic content. A subsequent annotation pipeline enriches these clips with detailed spatial and semantic information, including camera poses, depth maps, dynamic masks, structured captions, and serialized motion instructions. Analysis of SpatialVID's data statistics reveals a richness and diversity that directly foster improved model generalization and performance, establishing it as a key asset for the video and 3D vision research community.

We present S1-Omni, a unified multimodal reasoning model for scientific understanding, prediction, and generation. AI for Science (AI4S) has advanced significantly through domain-specific models, tool-augmented LLMs, and scientific language models. However, model capabilities remain highly fragmented, limiting the joint modeling of heterogeneous data, scientific laws, and expert knowledge. S1-Omni addresses this gap by consolidating these capabilities into a single, coherent scientific reasoning model. The architecture of S1-Omni is built upon three core components: unified representation of scientific data, natural-world knowledge alignment, and decoding for domain-specific tasks. First, S1-Omni maps natural-language instructions and scientific objects, including CIF, SMILES, protein sequences, spectra, and scientific images, into a shared representation space. Second, it incorporates scientific laws and expert knowledge into data construction and training, enabling the model to reason from scientific evidence. Third, it performs task-specific decoding to support a broad range of applications, including property prediction, spectrum-to-molecular generation, protein site and structure prediction, and scientific image generation and editing. S1-Omni is trained on S1-Omni-Corpus, which covers 200 scientific tasks and contains millions of reasoning samples, and is evaluated on over 60 scientific benchmarks. It outperforms GPT-5.5 and Gemini-3.1-Pro on most benchmarks and matches or surpasses domain-specific models on several benchmarks. Overall, S1-Omni provides a practical path toward unified scientific modeling.

Spatial reasoning is a foundational capability for multimodal large language models (MLLMs) to perceive and operate within the physical world. However, existing benchmarks predominantly rely on passive evaluation (e.g., static VQA) or simulator-specific pipelines, failing to assess general interactive spatial understanding. We introduce SpatialWorld, a unified benchmark designed specifically for evaluating the interactive spatial understanding of multimodal agents in complex real-world tasks. Integrating eight heterogeneous simulation backends under a shared, simulator-agnostic protocol, SpatialWorld features 760 human-annotated tasks across diverse domains (e.g., household routines, travel, social collaboration). Agents must solve tasks under vision-only partial observability, actively gathering egocentric visual evidence and expressing decisions via a unified, text-based action interface native to MLLMs. For reliable evaluation, each task includes a human-validated initial state, a reference trajectory, and a terminal-state verifier. Evaluating 15 advanced agents reveals that robust spatial task solving remains challenging: the strongest model, GPT-5, achieves an average task success rate (TSR) of only 17.4%, while the leading open-source model, Qwen-3.5, reaches 14.1%. Further analysis exposes a clear mismatch between task success and execution efficiency, alongside substantial domain-specific performance variations. These bottlenecks in active exploration and long-horizon planning position SpatialWorld as a rigorous testbed for future spatial agents.

The tumor microenvironment (TME) plays a central role in cancer progression, treatment response, and patient outcomes, yet large-scale, consistent, and quantitative TME characterization from routine hematoxylin and eosin (H&E)-stained histopathology remains scarce. We introduce OpenTME, an open-access dataset of pre-computed TME profiles derived from 3,634 H&E-stained whole-slide images across five cancer types (bladder, breast, colorectal, liver, and lung cancer) from The Cancer Genome Atlas (TCGA). All outputs were generated using Atlas H&E-TME, an AI-powered application built on the Atlas family of pathology foundation models, which performs tissue quality control, tissue segmentation, cell detection and classification, and spatial neighborhood analysis, yielding over 4,500 quantitative readouts per slide at cell-level resolution. OpenTME is available for non-commercial academic research on Hugging Face. We will continue to expand OpenTME over time and anticipate it will serve as a resource for biomarker discovery, spatial biology research, and the development of computational methods for TME analysis.

Understanding and reasoning about spatial relationships is a fundamental capability for Visual Question Answering (VQA) and robotics. While Vision Language Models (VLM) have demonstrated remarkable performance in certain VQA benchmarks, they still lack capabilities in 3D spatial reasoning, such as recognizing quantitative relationships of physical objects like distances or size differences. We hypothesize that VLMs' limited spatial reasoning capability is due to the lack of 3D spatial knowledge in training data and aim to solve this problem by training VLMs with Internet-scale spatial reasoning data. To this end, we present a system to facilitate this approach. We first develop an automatic 3D spatial VQA data generation framework that scales up to 2 billion VQA examples on 10 million real-world images. We then investigate various factors in the training recipe, including data quality, training pipeline, and VLM architecture. Our work features the first internet-scale 3D spatial reasoning dataset in metric space. By training a VLM on such data, we significantly enhance its ability on both qualitative and quantitative spatial VQA. Finally, we demonstrate that this VLM unlocks novel downstream applications in chain-of-thought spatial reasoning and robotics due to its quantitative estimation capability. Project website: https://spatial-vlm.github.io/

Incorporating spatial information, particularly those influenced by climate, weather, and demographic factors, is crucial for improving underwriting precision and enhancing risk management in insurance. However, spatial data are often unstructured, high-dimensional, and difficult to integrate into predictive models. Embedding methods are needed to convert spatial data into meaningful representations for modelling tasks. We propose a novel multi-view contrastive learning framework for generating spatial embeddings that combine information from multiple spatial data sources. To train the model, we construct a spatial dataset that merges satellite imagery and OpenStreetMap features across Europe. The framework aligns these spatial views with coordinate-based encodings, producing low-dimensional embeddings that capture both spatial structure and contextual similarity. Once trained, the model generates embeddings directly from latitude-longitude pairs, enabling any dataset with coordinates to be enriched with meaningful spatial features without requiring access to the original spatial inputs. In a case study on French real estate prices, we compare models trained on raw coordinates against those using our spatial embeddings as inputs. The embeddings consistently improve predictive accuracy across generalised linear, additive, and boosting models, while providing interpretable spatial effects and demonstrating transferability to unseen regions.

We present HistoAtlas, a pan-cancer computational atlas that extracts 38 interpretable histomic features from 6,745 diagnostic H&E slides across 21 TCGA cancer types and systematically links every feature to survival, gene expression, somatic mutations, and immune subtypes. All associations are covariate-adjusted, multiple-testing corrected, and classified into evidence-strength tiers. The atlas recovers known biology, from immune infiltration and prognosis to proliferation and kinase signaling, while uncovering compartment-specific immune signals and morphological subtypes with divergent outcomes. Every result is spatially traceable to tissue compartments and individual cells, statistically calibrated, and openly queryable. HistoAtlas enables systematic, large-scale biomarker discovery from routine H&E without specialized staining or sequencing. Data and an interactive web atlas are freely available at https://histoatlas.com .

Spatial understanding of the physical world from 2D visual inputs hinges on two complementary forms of geometric knowledge: holistic 3D structural perception and fine-grained metric scale estimation. Existing multimodal large language models (MLLMs) typically address only one facet, ingesting either depth maps or point clouds as additional model inputs, which incurs substantial computational overhead and inherits the generalization limitations of upstream prediction models. We propose GAMSI, a dual-pathway Geometry-Aware MLLM for Spatial Intelligence that takes only RGB images as input while internalizing both forms of geometric prior within a unified autoregressive backbone. Specifically, we introduce Metric-Structure Decoupled Queries (MSDQ) which employ two groups of learnable queries to respectively extract dense metric signals and sparse structural cues from the shared visual context, with a task-decoupled attention mask further preventing the two pathways from contaminating each other. Building on this, an Expert-Guided Visual Grounding (EVG) module projects the aggregated cues back to frame-level visual features and aligns them with vision foundation models, which serve purely as training-time supervision, rather than as model inputs. We further build a multi-task spatial instruction-tuning dataset (MTS) comprising 152{,}776 samples spanning 13 task types and three visual modalities, consolidated from six public datasets. Trained with a two-stage curriculum, GAMSI achieves state-of-the-art performance on seven spatial intelligence benchmarks.

Spatial reasoning is a key aspect of cognitive psychology and remains a major bottleneck for current vision-language models (VLMs). While extensive research has aimed to evaluate or improve VLMs' understanding of basic spatial relations, such as distinguishing left from right, near from far, and object counting, these tasks represent only the most fundamental level of spatial reasoning. In this work, we introduce OmniSpatial, a comprehensive and challenging benchmark for spatial reasoning, grounded in cognitive psychology. OmniSpatial covers four major categories: dynamic reasoning, complex spatial logic, spatial interaction, and perspective-taking, with 50 fine-grained subcategories. Through Internet data crawling and careful manual annotation, we construct over 1.5K question-answer pairs. Extensive experiments show that both open- and closed-source VLMs, as well as existing reasoning and spatial understanding models, exhibit significant limitations in comprehensive spatial understanding. We further analyze failure cases and propose potential directions for future research.

Multimodal agents in robotics, AR, and autonomous driving must reason about places and layouts from continuous egocentric streams, often using evidence outside the current view. Existing benchmarks either evaluate offline over full videos or target events rather than spatial structure. We introduce OVO-S-Bench, a fully human-annotated benchmark for streaming spatial intelligence, comprising 1,680 questions over 348 source videos. Annotation involves 12 trained annotators, each also serving as a blind cross-reviewer, across roughly 804 person-hours of multi-round quality assurance. Each question carries a query timestamp and an evidence interval, and at evaluation, the model sees only the prefix preceding the query. Questions span four levels of increasing abstraction: instantaneous egocentric perception, spatiotemporal context tracking, spatial simulation and reasoning, and allocentric mapping. Across 38 proprietary and open-source MLLMs, Gemini-3.1-Pro trails human experts by 27 points, 59.2 vs. 86.6, with allocentric mapping as the dominant bottleneck. Notably, streaming and spatially fine-tuned MLLMs underperform their own backbones. We further find that chain-of-thought reasoning amplifies spatial errors when ungrounded in the stream. By exposing these limitations, OVO-S-Bench establishes a demanding testbed for next-generation streaming spatial MLLMs.

In recent years, researchers have increasingly been interested in how to enable Multimodal Large Language Models (MLLM) to possess spatial understanding and reasoning capabilities. However, most existing methods overlook the importance of the ability to continuously work in an ever-changing world, and lack the possibility of deployment on embodied systems in real-world environments. In this work, we introduce OnlineSI, a framework that can continuously improve its spatial understanding of its surroundings given a video stream. Our core idea is to maintain a finite spatial memory to retain past observations, ensuring the size of the spatial memory does not increase as the input accumulates. We further integrate 3D point cloud information with semantic information, helping MLLM to better locate and identify objects in the scene. To evaluate our method, we introduce the Fuzzy F_1-Score to mitigate ambiguity, and test our method on two representative datasets. Experiments demonstrate the effectiveness of our method, paving the way towards real-world embodied systems.

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

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.

This work presents the first quantitative study of alignment errors between small uncrewed aerial systems (sUAS) geospatial imagery and a priori building polygons and finds that alignment errors are non-uniform and irregular. The work also introduces a publicly available dataset of imagery, building polygons, and human-generated and curated adjustments that can be used to evaluate existing strategies for aligning building polygons with sUAS imagery. There are no efforts that have aligned pre-existing spatial data with sUAS imagery, and thus, there is no clear state of practice. However, this effort and analysis show that the translational alignment errors present in this type of data, averaging 82px and an intersection over the union of 0.65, which would induce further errors and biases in downstream machine learning systems unless addressed. This study identifies and analyzes the translational alignment errors of 21,619 building polygons in fifty-one orthomosaic images, covering 16787.2 Acres (26.23 square miles), constructed from sUAS raw imagery from nine wide-area disasters (Hurricane Ian, Hurricane Harvey, Hurricane Michael, Hurricane Ida, Hurricane Idalia, Hurricane Laura, the Mayfield Tornado, the Musset Bayou Fire, and the Kilauea Eruption). The analysis finds no uniformity among the angle and distance metrics of the building polygon alignments as they present an average degree variance of 0.4 and an average pixel distance variance of 0.45. This work alerts the sUAS community to the problem of spatial alignment and that a simple linear transform, often used to align satellite imagery, will not be sufficient to align spatial data in sUAS orthomosaic imagery.

Learning feature representations of geographical space is vital for any machine learning model that integrates geolocated data, spanning application domains such as remote sensing, ecology, or epidemiology. Recent work mostly embeds coordinates using sine and cosine projections based on Double Fourier Sphere (DFS) features -- these embeddings assume a rectangular data domain even on global data, which can lead to artifacts, especially at the poles. At the same time, relatively little attention has been paid to the exact design of the neural network architectures these functional embeddings are combined with. This work proposes a novel location encoder for globally distributed geographic data that combines spherical harmonic basis functions, natively defined on spherical surfaces, with sinusoidal representation networks (SirenNets) that can be interpreted as learned Double Fourier Sphere embedding. We systematically evaluate the cross-product of positional embeddings and neural network architectures across various classification and regression benchmarks and synthetic evaluation datasets. In contrast to previous approaches that require the combination of both positional encoding and neural networks to learn meaningful representations, we show that both spherical harmonics and sinusoidal representation networks are competitive on their own but set state-of-the-art performances across tasks when combined. We provide source code at www.github.com/marccoru/locationencoder

Spatial reasoning ability is crucial for Vision Language Models (VLMs) to support real-world applications in diverse domains including robotics, augmented reality, and autonomous navigation. Unfortunately, existing benchmarks are inadequate in assessing spatial reasoning ability, especially the intrinsic-dynamic spatial reasoning which is a fundamental aspect of human spatial cognition. In this paper, we propose a unified benchmark, Spatial-DISE, based on a cognitively grounded taxonomy that categorizes tasks into four fundamental quadrants: Intrinsic-Static, Intrinsic-Dynamic, Extrinsic-Static, and Extrinsic-Dynamic spatial reasoning. Moreover, to address the issue of data scarcity, we develop a scalable and automated pipeline to generate diverse and verifiable spatial reasoning questions, resulting in a new Spatial-DISE dataset that includes Spatial-DISE Bench (559 evaluation VQA pairs) and Spatial-DISE-12K (12K+ training VQA pairs). Our comprehensive evaluation across 28 state-of-the-art VLMs reveals that, current VLMs have a large and consistent gap to human competence, especially on multi-step multi-view spatial reasoning. Spatial-DISE offers a robust framework, valuable dataset, and clear direction for future research toward human-like spatial intelligence. Benchmark, dataset, and code will be publicly released.

Humans possess spatial reasoning abilities that enable them to understand spaces through multimodal observations, such as vision and sound. Large multimodal reasoning models extend these abilities by learning to perceive and reason, showing promising performance across diverse spatial tasks. However, systematic reviews and publicly available benchmarks for these models remain limited. In this survey, we provide a comprehensive review of multimodal spatial reasoning tasks with large models, categorizing recent progress in multimodal large language models (MLLMs) and introducing open benchmarks for evaluation. We begin by outlining general spatial reasoning, focusing on post-training techniques, explainability, and architecture. Beyond classical 2D tasks, we examine spatial relationship reasoning, scene and layout understanding, as well as visual question answering and grounding in 3D space. We also review advances in embodied AI, including vision-language navigation and action models. Additionally, we consider emerging modalities such as audio and egocentric video, which contribute to novel spatial understanding through new sensors. We believe this survey establishes a solid foundation and offers insights into the growing field of multimodal spatial reasoning. Updated information about this survey, codes and implementation of the open benchmarks can be found at https://github.com/zhengxuJosh/Awesome-Spatial-Reasoning.

Precise spatial modeling in the operating room (OR) is foundational to many clinical tasks, supporting intraoperative awareness, hazard avoidance, and surgical decision-making. While existing approaches leverage large-scale multimodal datasets for latent-space alignment to implicitly learn spatial relationships, they overlook the 3D capabilities of MLLMs. However, this approach raises two issues: (1) Operating rooms typically lack multiple video and audio sensors, making multimodal 3D data difficult to obtain; (2) Training solely on readily available 2D data fails to capture fine-grained details in complex scenes. To address this gap, we introduce Spatial-ORMLLM, the first large vision-language model for 3D spatial reasoning in operating rooms using only RGB modality to infer volumetric and semantic cues, enabling downstream medical tasks with detailed and holistic spatial context. Spatial-ORMLLM incorporates a Spatial-Enhanced Feature Fusion Block, which integrates 2D modality inputs with rich 3D spatial knowledge extracted by the estimation algorithm and then feeds the combined features into the visual tower. By employing a unified end-to-end MLLM framework, it combines powerful spatial features with textual features to deliver robust 3D scene reasoning without any additional expert annotations or sensor inputs. Experiments on multiple benchmark clinical datasets demonstrate that Spatial-ORMLLM achieves state-of-the-art performance and generalizes robustly to previously unseen surgical scenarios and downstream tasks.

Spatial reasoning is a fundamental aspect of human cognition, yet it remains a major challenge for contemporary vision-language models (VLMs). Prior work largely relied on synthetic or LLM-generated environments with limited task designs and puzzle-like setups, failing to capture the real-world complexity, visual noise, and diverse spatial relationships that VLMs encounter. To address this, we introduce SpatiaLab, a comprehensive benchmark for evaluating VLMs' spatial reasoning in realistic, unconstrained contexts. SpatiaLab comprises 1,400 visual question-answer pairs across six major categories: Relative Positioning, Depth & Occlusion, Orientation, Size & Scale, Spatial Navigation, and 3D Geometry, each with five subcategories, yielding 30 distinct task types. Each subcategory contains at least 25 questions, and each main category includes at least 200 questions, supporting both multiple-choice and open-ended evaluation. Experiments across diverse state-of-the-art VLMs, including open- and closed-source models, reasoning-focused, and specialized spatial reasoning models, reveal a substantial gap in spatial reasoning capabilities compared with humans. In the multiple-choice setup, InternVL3.5-72B achieves 54.93% accuracy versus 87.57% for humans. In the open-ended setting, all models show a performance drop of around 10-25%, with GPT-5-mini scoring highest at 40.93% versus 64.93% for humans. These results highlight key limitations in handling complex spatial relationships, depth perception, navigation, and 3D geometry. By providing a diverse, real-world evaluation framework, SpatiaLab exposes critical challenges and opportunities for advancing VLMs' spatial reasoning, offering a benchmark to guide future research toward robust, human-aligned spatial understanding. SpatiaLab is available at: https://spatialab-reasoning.github.io/.

The spatio-temporal relations of impacts of extreme events and their drivers in climate data are not fully understood and there is a need of machine learning approaches to identify such spatio-temporal relations from data. The task, however, is very challenging since there are time delays between extremes and their drivers, and the spatial response of such drivers is inhomogeneous. In this work, we propose a first approach and benchmarks to tackle this challenge. Our approach is trained end-to-end to predict spatio-temporally extremes and spatio-temporally drivers in the physical input variables jointly. By enforcing the network to predict extremes from spatio-temporal binary masks of identified drivers, the network successfully identifies drivers that are correlated with extremes. We evaluate our approach on three newly created synthetic benchmarks, where two of them are based on remote sensing or reanalysis climate data, and on two real-world reanalysis datasets. The source code and datasets are publicly available at the project page https://hakamshams.github.io/IDE.

Spatial intelligence requires visual representations that capture both semantic objects and geometric structure in the physical world. To support this, two major pre-training schemes are now widely used as foundation backbones: Vision-Language Models (VLMs), which use language supervision to align visual observations with semantic concepts, and Video Generation Models (VGMs), which learn from temporally evolving visual worlds. However, it still remains unclear which pre-training scheme provides a better representation substrate for spatial intelligence. In this paper, we present the first systematic frozen-feature probing study of VLMs and VGMs across three representative axes of spatial intelligence: semantic tagging, instance grouping, and 3D geometry prediction. Using the lightweight probe, our framework enables a controlled comparison of what information is already encoded in frozen representations from two model families. Experimental results reveal a clear complementarity: VLMs are stronger at semantic tagging and instance grouping, while VGMs provide more accessible signals for dense geometry and camera motion. Moreover, a naive fusion of the two already yields a representation that excels at both geometry and semantics, suggesting a promising direction for building stronger spatial-intelligence backbones by effectively integrating features from both model families. Our code is available at https://github.com/om-ai-lab/Probing-VLM-VGM{https://github.com/om-ai-lab/Probing-VLM-VGM}.

Multimodal Large Language Models (MLLMs) have demonstrated impressive performance in general vision-language tasks. However, recent studies have exposed critical limitations in their spatial reasoning capabilities. This deficiency in spatial reasoning significantly constrains MLLMs' ability to interact effectively with the physical world, thereby limiting their broader applications. We argue that spatial reasoning capabilities will not naturally emerge from merely scaling existing architectures and training methodologies. Instead, this challenge demands dedicated attention to fundamental modifications in the current MLLM development approach. In this position paper, we first establish a comprehensive framework for spatial reasoning within the context of MLLMs. We then elaborate on its pivotal role in real-world applications. Through systematic analysis, we examine how individual components of the current methodology, from training data to reasoning mechanisms, influence spatial reasoning capabilities. This examination reveals critical limitations while simultaneously identifying promising avenues for advancement. Our work aims to direct the AI research community's attention toward these crucial yet underexplored aspects. By highlighting these challenges and opportunities, we seek to catalyze progress toward achieving human-like spatial reasoning capabilities in MLLMs.

Not yet. We present SPACE, a benchmark that systematically evaluates spatial cognition in frontier models. Our benchmark builds on decades of research in cognitive science. It evaluates large-scale mapping abilities that are brought to bear when an organism traverses physical environments, smaller-scale reasoning about object shapes and layouts, and cognitive infrastructure such as spatial attention and memory. For many tasks, we instantiate parallel presentations via text and images, allowing us to benchmark both large language models and large multimodal models. Results suggest that contemporary frontier models fall short of the spatial intelligence of animals, performing near chance level on a number of classic tests of animal cognition.

The cycle of scientific discovery is frequently bottlenecked by the slow, manual creation of software to support computational experiments. To address this, we present an AI system that creates expert-level scientific software whose goal is to maximize a quality metric. The system uses a Large Language Model (LLM) and Tree Search (TS) to systematically improve the quality metric and intelligently navigate the large space of possible solutions. The system achieves expert-level results when it explores and integrates complex research ideas from external sources. The effectiveness of tree search is demonstrated across a wide range of benchmarks. In bioinformatics, it discovered 40 novel methods for single-cell data analysis that outperformed the top human-developed methods on a public leaderboard. In epidemiology, it generated 14 models that outperformed the CDC ensemble and all other individual models for forecasting COVID-19 hospitalizations. Our method also produced state-of-the-art software for geospatial analysis, neural activity prediction in zebrafish, time series forecasting and numerical solution of integrals. By devising and implementing novel solutions to diverse tasks, the system represents a significant step towards accelerating scientific progress.

Precise spatial understanding in Earth Observation is essential for translating raw aerial imagery into actionable insights for critical applications like urban planning, environmental monitoring and disaster management. However, Multimodal Large Language Models exhibit critical deficiencies in fine-grained spatial understanding within Remote Sensing, primarily due to a reliance on limited or repurposed legacy datasets. To bridge this gap, we introduce a large-scale dataset grounded in verifiable cadastral vector data, comprising 3.8 million annotated objects across 510k high-resolution images with 135 granular semantic categories. We validate this resource through a comprehensive instruction-tuning benchmark spanning seven spatial reasoning tasks. Our evaluation establishes a robust baseline using a standard LLaVA architecture. We show that while current RS-specialized and commercial models (e.g., Gemini) struggle in zero-shot settings, high-fidelity supervision effectively bridges this gap, enabling standard architectures to master fine-grained spatial grounding without complex architectural modifications.

The integration of Large Language Models (LLMs) into Geographic Information Systems (GIS) marks a paradigm shift toward autonomous spatial analysis. However, evaluating these LLM-based agents remains challenging due to the complex, multi-step nature of geospatial workflows. Existing benchmarks primarily rely on static text or code matching, neglecting dynamic runtime feedback and the multimodal nature of spatial outputs. To address this gap, we introduce GeoAgentBench (GABench), a dynamic and interactive evaluation benchmark tailored for tool-augmented GIS agents. GABench provides a realistic execution sandbox integrating 117 atomic GIS tools, encompassing 53 typical spatial analysis tasks across 6 core GIS domains. Recognizing that precise parameter configuration is the primary determinant of execution success in dynamic GIS environments, we designed the Parameter Execution Accuracy (PEA) metric, which utilizes a "Last-Attempt Alignment" strategy to quantify the fidelity of implicit parameter inference. Complementing this, a Vision-Language Model (VLM) based verification is proposed to assess data-spatial accuracy and cartographic style adherence. Furthermore, to address the frequent task failures caused by parameter misalignments and runtime anomalies, we developed a novel agent architecture, Plan-and-React, that mimics expert cognitive workflows by decoupling global orchestration from step-wise reactive execution. Extensive experiments with seven representative LLMs demonstrate that the Plan-and-React paradigm significantly outperforms traditional frameworks, achieving the optimal balance between logical rigor and execution robustness, particularly in multi-step reasoning and error recovery. Our findings highlight current capability boundaries and establish a robust standard for assessing and advancing the next generation of autonomous GeoAI.

Gene expression prediction, which predicts mRNA expression levels from DNA sequences, presents significant challenges. Previous works often focus on extending input sequence length to locate distal enhancers, which may influence target genes from hundreds of kilobases away. Our work first reveals that for current models, long sequence modeling can decrease performance. Even carefully designed algorithms only mitigate the performance degradation caused by long sequences. Instead, we find that proximal multimodal epigenomic signals near target genes prove more essential. Hence we focus on how to better integrate these signals, which has been overlooked. We find that different signal types serve distinct biological roles, with some directly marking active regulatory elements while others reflect background chromatin patterns that may introduce confounding effects. Simple concatenation may lead models to develop spurious associations with these background patterns. To address this challenge, we propose Prism, a framework that learns multiple combinations of high-dimensional epigenomic features to represent distinct background chromatin states and uses backdoor adjustment to mitigate confounding effects. Our experimental results demonstrate that proper modeling of multimodal epigenomic signals achieves state-of-the-art performance using only short sequences for gene expression prediction.

Spatial competence is the quality of maintaining a consistent internal representation of an environment and using it to infer discrete structure and plan actions under constraints. Prevailing spatial evaluations for large models are limited to probing isolated primitives through 3D transformations or visual question answering. We introduce the Spatial Competence Benchmark (SCBench), spanning three hierarchical capability buckets whose tasks require executable outputs verified by deterministic checkers or simulator-based evaluators. On SCBench, three frontier models exhibit monotonically decreasing accuracy up the capability ladder. Sweeping output-token caps shows that accuracy gains concentrate at low budgets and saturate quickly, and failures are dominated by locally plausible geometry that breaks global constraints. We release the task generators, verifiers, and visualisation tooling.

Rapid growth of high-dimensional datasets in fields such as single-cell RNA sequencing and spatial genomics has led to unprecedented opportunities for scientific discovery, but it also presents unique computational and statistical challenges. Traditional methods struggle with geometry-aware data generation, interpolation along meaningful trajectories, and transporting populations via feasible paths. To address these issues, we introduce Geometry-Aware Generative Autoencoder (GAGA), a novel framework that combines extensible manifold learning with generative modeling. GAGA constructs a neural network embedding space that respects the intrinsic geometries discovered by manifold learning and learns a novel warped Riemannian metric on the data space. This warped metric is derived from both the points on the data manifold and negative samples off the manifold, allowing it to characterize a meaningful geometry across the entire latent space. Using this metric, GAGA can uniformly sample points on the manifold, generate points along geodesics, and interpolate between populations across the learned manifold using geodesic-guided flows. GAGA shows competitive performance in simulated and real-world datasets, including a 30% improvement over the state-of-the-art methods in single-cell population-level trajectory inference.

Driven by the demand for spatial intelligence and holistic scene perception, omnidirectional images (ODIs), which provide a complete 360 field of view, are receiving growing attention across diverse applications such as virtual reality, autonomous driving, and embodied robotics. Despite their unique characteristics, ODIs exhibit remarkable differences from perspective images in geometric projection, spatial distribution, and boundary continuity, making it challenging for direct domain adaption from perspective methods. This survey reviews recent panoramic vision techniques with a particular emphasis on the perspective-to-panorama adaptation. We first revisit the panoramic imaging pipeline and projection methods to build the prior knowledge required for analyzing the structural disparities. Then, we summarize three challenges of domain adaptation: severe geometric distortions near the poles, non-uniform sampling in Equirectangular Projection (ERP), and periodic boundary continuity. Building on this, we cover 20+ representative tasks drawn from more than 300 research papers in two dimensions. On one hand, we present a cross-method analysis of representative strategies for addressing panoramic specific challenges across different tasks. On the other hand, we conduct a cross-task comparison and classify panoramic vision into four major categories: visual quality enhancement and assessment, visual understanding, multimodal understanding, and visual generation. In addition, we discuss open challenges and future directions in data, models, and applications that will drive the advancement of panoramic vision research. We hope that our work can provide new insight and forward looking perspectives to advance the development of panoramic vision technologies. Our project page is https://insta360-research-team.github.io/Survey-of-Panorama

Multimodal large language models (MLLMs) have shown remarkable capabilities across a broad range of tasks but their knowledge and abilities in the geographic and geospatial domains are yet to be explored, despite potential wide-ranging benefits to navigation, environmental research, urban development, and disaster response. We conduct a series of experiments exploring various vision capabilities of MLLMs within these domains, particularly focusing on the frontier model GPT-4V, and benchmark its performance against open-source counterparts. Our methodology involves challenging these models with a small-scale geographic benchmark consisting of a suite of visual tasks, testing their abilities across a spectrum of complexity. The analysis uncovers not only where such models excel, including instances where they outperform humans, but also where they falter, providing a balanced view of their capabilities in the geographic domain. To enable the comparison and evaluation of future models, our benchmark will be publicly released.

Spatial intelligence refers to the ability to perceive, reason about, and describe objects and their relationships within three-dimensional environments, forming a foundation for embodied perception and scene understanding. 3D captioning aims to describe 3D scenes in natural language; however, it remains challenging due to the sparsity and irregularity of point clouds and, more critically, the weak grounding and limited out-of-distribution (OOD) generalization of existing captioners across drastically different environments, including indoor and outdoor 3D scenes. To address this challenge, we propose 3D CoCa v2, a generalizable 3D captioning framework that unifies contrastive vision-language learning with 3D caption generation and further improves robustness via test-time search (TTS) without updating the captioner parameters. 3D CoCa v2 builds on a frozen CLIP-based semantic prior, a spatially-aware 3D scene encoder for geometry, and a multimodal decoder jointly optimized with contrastive and captioning objectives, avoiding external detectors or handcrafted proposals. At inference, TTS produces diverse caption candidates and performs reward-guided selection using a compact scene summary. Experiments show improvements over 3D CoCa of +1.50 CIDEr@0.5IoU on ScanRefer and +1.61 CIDEr@0.5IoU on Nr3D, and +3.8 CIDEr@0.25 in zero-shot OOD evaluation on TOD3Cap. Code will be released at https://github.com/AIGeeksGroup/3DCoCav2.

Benchmarking spatial reasoning in multimodal large language models (MLLMs) has attracted growing interest in computer vision due to its importance for embodied AI and other agentic systems that require precise interaction with the physical world. However, spatial reasoning on Earth imagery has lagged behind, as it uniquely involves grounding objects in georeferenced images and quantitatively reasoning about distances, directions, and topological relations using both visual cues and vector geometry coordinates (e.g., 2D bounding boxes, polylines, and polygons). Existing benchmarks for Earth imagery primarily focus on 2D spatial grounding, image captioning, and coarse spatial relations (e.g., simple directional or proximity cues). They lack support for quantitative direction and distance reasoning, systematic topological relations, and complex object geometries beyond bounding boxes. To fill this gap, we propose EarthSpatialBench, a comprehensive benchmark for evaluating spatial reasoning in MLLMs on Earth imagery. The benchmark contains over 325K question-answer pairs spanning: (1) qualitative and quantitative reasoning about spatial distance and direction; (2) systematic topological relations; (3) single-object queries, object-pair queries, and compositional aggregate group queries; and (4) object references expressed via textual descriptions, visual overlays, and explicit geometry coordinates, including 2D bounding boxes, polylines, and polygons. We conducted extensive experiments on both open-source and proprietary models to identify limitations in the spatial reasoning of MLLMs.

Spatial reasoning is a fundamental capability of embodied agents and has garnered widespread attention in the field of multimodal large language models (MLLMs). In this work, we propose a novel benchmark, Open3DVQA, to comprehensively evaluate the spatial reasoning capacities of current state-of-the-art (SOTA) foundation models in open 3D space. Open3DVQA consists of 9k VQA samples, collected using an efficient semi-automated tool in a high-fidelity urban simulator. We evaluate several SOTA MLLMs across various aspects of spatial reasoning, such as relative and absolute spatial relationships, situational reasoning, and object-centric spatial attributes. Our results reveal that: 1) MLLMs perform better at answering questions regarding relative spatial relationships than absolute spatial relationships, 2) MLLMs demonstrate similar spatial reasoning abilities for both egocentric and allocentric perspectives, and 3) Fine-tuning large models significantly improves their performance across different spatial reasoning tasks. We believe that our open-source data collection tools and in-depth analyses will inspire further research on MLLM spatial reasoning capabilities. The benchmark is available at https://github.com/WeichenZh/Open3DVQA.

The next Point-of-Interest (POI) recommendation task aims to predict users' next destinations based on their historical movement data and plays a key role in location-based services and personalized applications. Accurate next POI recommendation depends on effectively modeling geographic information and POI transition relations, which are crucial for capturing spatial dependencies and user movement patterns. While Large Language Models (LLMs) exhibit strong capabilities in semantic understanding and contextual reasoning, applying them to spatial tasks like next POI recommendation remains challenging. First, the infrequent nature of specific GPS coordinates makes it difficult for LLMs to model precise spatial contexts. Second, the lack of knowledge about POI transitions limits their ability to capture potential POI-POI relationships. To address these issues, we propose GA-LLM (Geography-Aware Large Language Model), a novel framework that enhances LLMs with two specialized components. The Geographic Coordinate Injection Module (GCIM) transforms GPS coordinates into spatial representations using hierarchical and Fourier-based positional encoding, enabling the model to understand geographic features from multiple perspectives. The POI Alignment Module (PAM) incorporates POI transition relations into the LLM's semantic space, allowing it to infer global POI relationships and generalize to unseen POIs. Experiments on three real-world datasets demonstrate the state-of-the-art performance of GA-LLM.

Current evaluations of spatial intelligence can be systematically invalid under modern vision-language model (VLM) settings. First, many benchmarks derive question-answer (QA) pairs from point-cloud-based 3D annotations originally curated for traditional 3D perception. When such annotations are treated as ground truth for video-based evaluation, reconstruction and annotation artifacts can miss objects that are clearly visible in the video, mislabel object identities, or corrupt geometry-dependent answers (e.g., size), yielding incorrect or ambiguous QA pairs. Second, evaluations often assume full-scene access, while many VLMs operate on sparsely sampled frames (e.g., 16-64), making many questions effectively unanswerable under the actual model inputs. We improve evaluation validity by introducing ReVSI, a benchmark and protocol that ensures each QA pair is answerable and correct under the model's actual inputs. To this end, we re-annotate objects and geometry across 381 scenes from 5 datasets to improve data quality, and regenerate all QA pairs with rigorous bias mitigation and human verification using professional 3D annotation tools. We further enhance evaluation controllability by providing variants across multiple frame budgets (16/32/64/all) and fine-grained object visibility metadata, enabling controlled diagnostic analyses. Evaluations of general and domain-specific VLMs on ReVSI reveal systematic failure modes that are obscured by prior benchmarks, yielding a more reliable and diagnostic assessment of spatial intelligence.

Spatial cognition is fundamental to real-world multimodal intelligence, allowing models to effectively interact with the physical environment. While multimodal large language models (MLLMs) have made significant strides, existing benchmarks often oversimplify spatial cognition, reducing it to a single-dimensional metric, which fails to capture the hierarchical structure and interdependence of spatial abilities. To address this gap, we propose a hierarchical spatial cognition framework that decomposes spatial intelligence into five progressively complex levels from basic observation to high-level planning. Building upon this taxonomy, we construct SpatialBench, a large-scale, fine-grained benchmark covering 15 tasks aligned with these cognitive levels. To provide a unified evaluation across heterogeneous tasks, we further introduce a high-level capability-oriented metric that reliably assesses a model's overall spatial reasoning ability. Extensive experiments over massive MLLMs reveal distinct performance stratification across cognitive levels: models exhibit strong perceptual grounding yet remain limited in symbolic reasoning, causal inference, and planning. Additional human tests demonstrate that humans perform selective, goal-directed abstraction, while MLLMs tend to over-attend to surface details without coherent spatial intent. Our work establishes the first systematic framework for measuring hierarchical spatial cognition in MLLMs, laying the foundation for future spatially intelligent systems.

The field of Earth Observations (EO) offers a wealth of data from diverse sensors, presenting a great opportunity for advancing self-supervised multimodal learning. However, current multimodal EO datasets and models focus on a single data type, either mono-date images or time series, which limits their expressivity. We introduce OmniSat, a novel architecture that exploits the spatial alignment between multiple EO modalities to learn expressive multimodal representations without labels. To demonstrate the advantages of combining modalities of different natures, we augment two existing datasets with new modalities. As demonstrated on three downstream tasks: forestry, land cover classification, and crop mapping. OmniSat can learn rich representations in an unsupervised manner, leading to improved performance in the semi- and fully-supervised settings, even when only one modality is available for inference. The code and dataset are available at github.com/gastruc/OmniSat.

Earth observation data such as satellite imagery can, when combined with machine learning, have profound impacts on our understanding of the geography of poverty through the prediction of living conditions, especially where government-derived economic indicators are either unavailable or potentially untrustworthy. Recent work has progressed in using EO data not only to predict spatial economic outcomes, but also to explore cause and effect, an understanding which is critical for downstream policy analysis. In this review, we first document the growth of interest in EO-ML analyses in the causal space. We then trace the relationship between spatial statistics and EO-ML methods before discussing the four ways in which EO data has been used in causal ML pipelines -- (1.) poverty outcome imputation for downstream causal analysis, (2.) EO image deconfounding, (3.) EO-based treatment effect heterogeneity, and (4.) EO-based transportability analysis. We conclude by providing a workflow for how researchers can incorporate EO data in causal ML analysis going forward.

Holistic 3D modeling of molecularly defined brain structures is crucial for understanding complex brain functions. Emerging tissue profiling technologies enable the construction of a comprehensive atlas of the mammalian brain with sub-cellular resolution and spatially resolved gene expression data. However, such tera-scale volumetric datasets present significant computational challenges in understanding complex brain functions within their native 3D spatial context. Here, we propose the novel generative approach Tera-MIND, which can simulate Tera-scale Mouse braINs in 3D using a patch-based and boundary-aware Diffusion model. Taking spatial transcriptomic data as the conditional input, we generate virtual mouse brains with comprehensive cellular morphological detail at teravoxel scale. Through the lens of 3D gene-gene self-attention, we identify spatial molecular interactions for key transcriptomic pathways in the murine brain, exemplified by glutamatergic and dopaminergic neuronal systems. Importantly, these in-silico biological findings are consistent and reproducible across three tera-scale virtual mouse brains. Therefore, Tera-MIND showcases a promising path toward efficient and generative simulations of whole organ systems for biomedical research. Project website: http://musikisomorphie.github.io/Tera-MIND.html{https}

Accurate spatiotemporal pattern analysis is critical in fields such as urban traffic, meteorology, and public health monitoring. However, existing methods face performance bottlenecks, typically yielding only incremental gains and often exhibiting limited cross-domain transferability. We analyze this bottleneck through spatial and temporal entropy measures, which are used as diagnostic indicators of spatiotemporal complexity mismatch rather than as guarantees that entropy alignment alone yields better forecasting. Empirically, larger mismatch is often accompanied by higher prediction uncertainty, especially under a fixed model-capacity budget. Guided by this diagnostic, we propose a scalable, adaptive framework that harmonizes spatial and temporal feature representations. Spatial dimensionality is compressed via low-rank matrix embedding to preserve essential structure, while an extended temporal horizon captures long-range dependencies and mitigates cumulative errors arising from temporal heterogeneity. Extensive experiments on urban traffic, meteorological, and epidemic datasets demonstrate substantial accuracy gains and broad applicability across the evaluated domains, suggesting that the framework is promising for a wide range of spatiotemporal tasks beyond the current study. The code is available on GitHub at https://github.com/ST-Balance/ST-Balance.

Many data have an underlying dependence on spatial location; it may be weather on the Earth, a simulation on a mesh, or a registered image. Yet this feature is rarely taken advantage of, and violates common assumptions made by many neural network layers, such as translation equivariance. Further, many works that do incorporate locality fail to capture fine-grained structure. To address this, we introduce the Spatial Mixture-of-Experts (SMoE) layer, a sparsely-gated layer that learns spatial structure in the input domain and routes experts at a fine-grained level to utilize it. We also develop new techniques to train SMoEs, including a self-supervised routing loss and damping expert errors. Finally, we show strong results for SMoEs on numerous tasks, and set new state-of-the-art results for medium-range weather prediction and post-processing ensemble weather forecasts.

Spatial reasoning is a fundamental capability for vision-language models (VLMs) deployed in real-world environments. However, visual observations are inherently limited representations of a 3D world: occlusion can render objects invisible, and perspective can make geometric properties misleading. Despite this, existing spatial reasoning benchmarks typically assume that observations are sufficient and reliable, focusing on whether models produce correct answers rather than whether they recognize when a question cannot be answered and what additional observations would be needed. In this work, we challenge this assumption by constructing a controlled evaluation framework, SpatialUncertain, and introducing two types of observation challenges: (1) occlusion, which hides target information, and (2) perspective ambiguity, which produces misleading visual cues. For each configuration, we design spatial questions that are answerable under clean observations but require abstention under the introduced challenges. We further evaluate whether models can identify which additional viewpoints would resolve perspective ambiguity. Our results across a diverse set of frontier open- and closed-source VLMs reveal two consistent failure modes. First, models are prone to overconfident answering, attempting to solve spatial reasoning tasks even when visual evidence is incomplete or misleading, with average accuracy around 30\% under occlusion and below 10\% under perspective ambiguity. Second, even when additional views are available, some models perform near random chance in identifying which would provide reliable evidence. Together, our findings call for moving beyond answer correctness toward evaluating whether models know when to abstain and how to seek reliable evidence.

Geolocating images of a ground-level scene entails estimating the location on Earth where the picture was taken, in absence of GPS or other location metadata. Typically, methods are evaluated by measuring the Great Circle Distance (GCD) between a predicted location and ground truth. However, this measurement is limited because it only evaluates a single point, not estimates of regions or score heatmaps. This is especially important in applications to rural, wilderness and under-sampled areas, where finding the exact location may not be possible, and when used in aggregate systems that progressively narrow down locations. In this paper, we introduce a novel metric, Recall vs Area (RvA), which measures the accuracy of estimated distributions of locations. RvA treats image geolocation results similarly to document retrieval, measuring recall as a function of area: For a ranked list of (possibly non-contiguous) predicted regions, we measure the accumulated area required for the region to contain the ground truth coordinate. This produces a curve similar to a precision-recall curve, where "precision" is replaced by square kilometers area, allowing evaluation of performance for different downstream search area budgets. Following directly from this view of the problem, we then examine a simple ensembling approach to global-scale image geolocation, which incorporates information from multiple sources to help address domain shift, and can readily incorporate multiple models, attribute predictors, and data sources. We study its effectiveness by combining the geolocation models GeoEstimation and the current SOTA GeoCLIP, with attribute predictors based on ORNL LandScan and ESA-CCI Land Cover. We find significant improvements in image geolocation for areas that are under-represented in the training set, particularly non-urban areas, on both Im2GPS3k and Street View images.

We present OSMGraphCLIP, a CLIP-style geospatial representation model that learns global location embeddings from freely available OpenStreetMap (OSM) data. OSMGraphCLIP represents geographic environments as heterogeneous graphs of typed OSM features, preserving the topological and semantic relationships among roads, buildings, land-use regions, and points of interest. A multi-scale graph encoder captures both fine-grained local structure and broader landscape composition, and supervises a spherical-harmonics location encoder through a contrastive alignment objective. We evaluate OSMGraphCLIP across a diverse suite of downstream geospatial regression and classification tasks spanning climate, ecology, socioeconomic indicators, public health, land cover, biodiversity, and wildfire forecasting, and show that structured OSM data alone supports strong global location representations across domains. OSMGraphCLIP matches or exceeds satellite-based baselines on the majority of benchmarks, with the most pronounced advantage on socioeconomic and public-health tasks, where OSM's explicit semantic annotation of the built environment encodes patterns of human activity that satellite pixels can only capture indirectly. On ecological and environmental tasks, the model remains closely competitive with imagery-based methods despite using no Earth observation data. Qualitative analysis confirms that the learned embeddings organize geographic space coherently, recovering biome boundaries, urban gradients, and tropical--temperate distinctions from map topology alone.

In precision medicine, quantitative multi-omic features, topological context, and textual biological knowledge play vital roles in identifying disease-critical signaling pathways and targets. Existing pipelines capture only part of these-numerical omics ignore topological context, text-centric LLMs lack quantitative grounded reasoning, and graph-only models underuse node semantics and the generalization of LLMs-limiting mechanistic interpretability. Although Process Reward Models (PRMs) aim to guide reasoning in LLMs, they remain limited by unreliable intermediate evaluation, and vulnerability to reward hacking with computational cost. These gaps motivate integrating quantitative multi-omic signals, topological structure with node annotations, and literature-scale text via LLMs, using subgraph reasoning as the principle bridge linking numeric evidence, topological knowledge and language context. Therefore, we propose GALAX (Graph Augmented LAnguage model with eXplainability), an innovative framework that integrates pretrained Graph Neural Networks (GNNs) into Large Language Models (LLMs) via reinforcement guided by a Graph Process Reward Model (GPRM), which generates disease-relevant subgraphs in a step-wise manner initiated by an LLM and iteratively evaluated by a pretrained GNN, enabling process-level supervision without explicit intermediate reasoning annotations. As an application, we also introduced Target-QA, a benchmark combining CRISPR-identified targets, multi-omic profiles, and biomedical graph knowledge across diverse cancer cell lines, which enables GNN pretraining for supervising step-wise graph construction and supports long-context reasoning over text-numeric graphs (TNGs), providing a scalable and biologically grounded framework for explainable, reinforcement-guided subgraph reasoning toward reliable and interpretable target and pathway discovery in precision medicine.

Recent advances in multimodal large language models (MLLMs) have significantly enhanced their capabilities; however, their spatial perception abilities remain a notable limitation. To address this challenge, multimodal data synthesis offers a promising solution. Yet, ensuring that synthesized data adhere to spatial common sense is a non-trivial task. In this work, we introduce SKG2Data, a novel multimodal synthesis approach guided by spatial knowledge graphs, grounded in the concept of knowledge-to-data generation. SKG2Data automatically constructs a Spatial Knowledge Graph (SKG) to emulate human-like perception of spatial directions and distances, which is subsequently utilized to guide multimodal data synthesis. Extensive experiments demonstrate that data synthesized from diverse types of spatial knowledge, including direction and distance, not only enhance the spatial perception and reasoning abilities of MLLMs but also exhibit strong generalization capabilities. We hope that the idea of knowledge-based data synthesis can advance the development of spatial intelligence.

Multi-modal models have achieved remarkable progress in recent years. Nevertheless, they continue to exhibit notable limitations in spatial understanding and reasoning, which are fundamental capabilities to achieving artificial general intelligence. With the recent release of GPT-5, allegedly the most powerful AI model to date, it is timely to examine where the leading models stand on the path toward spatial intelligence. First, we propose a comprehensive taxonomy of spatial tasks that unifies existing benchmarks and discuss the challenges in ensuring fair evaluation. We then evaluate state-of-the-art proprietary and open-source models on eight key benchmarks, at a cost exceeding one billion total tokens. Our empirical study reveals that (1) GPT-5 demonstrates unprecedented strength in spatial intelligence, yet (2) still falls short of human performance across a broad spectrum of tasks. Moreover, we (3) identify the more challenging spatial intelligence problems for multi-modal models, and (4) proprietary models do not exhibit a decisive advantage when facing the most difficult problems. In addition, we conduct a qualitative evaluation across a diverse set of scenarios that are intuitive for humans yet fail even the most advanced multi-modal models.

While large language models have become the prevailing approach for agentic reasoning and planning, their success in symbolic domains does not readily translate to the physical world. Spatial intelligence, the ability to perceive 3D structure, reason about object relationships, and act under physical constraints, is an orthogonal capability that proves important for embodied agents. Existing surveys address either agentic architectures or spatial domains in isolation. None provide a unified framework connecting these complementary capabilities. This paper bridges that gap. Through a thorough review of over 2,000 papers, citing 742 works from top-tier venues, we introduce a unified three-axis taxonomy connecting agentic capabilities with spatial tasks across scales. Crucially, we distinguish spatial grounding (metric understanding of geometry and physics) from symbolic grounding (associating images with text), arguing that perception alone does not confer agency. Our analysis reveals three key findings mapped to these axes: (1) hierarchical memory systems (Capability axis) are important for long-horizon spatial tasks. (2) GNN-LLM integration (Task axis) is a promising approach for structured spatial reasoning. (3) World models (Scale axis) are essential for safe deployment across micro-to-macro spatial scales. We conclude by identifying six grand challenges and outlining directions for future research, including the need for unified evaluation frameworks to standardize cross-domain assessment. This taxonomy provides a foundation for unifying fragmented research efforts and enabling the next generation of spatially-aware autonomous systems in robotics, autonomous vehicles, and geospatial intelligence.

Recent advances in vision-language models (VLMs) have enabled powerful multimodal reasoning, but state-of-the-art approaches typically rely on extremely large models with prohibitive computational and memory requirements. This makes their deployment challenging in resource-constrained environments such as warehouses, robotics, and industrial applications, where both efficiency and robust spatial understanding are critical. In this work, we present SmolRGPT, a compact vision-language architecture that explicitly incorporates region-level spatial reasoning by integrating both RGB and depth cues. SmolRGPT employs a three-stage curriculum that progressively align visual and language features, enables spatial relationship understanding, and adapts to task-specific datasets. We demonstrate that with only 600M parameters, SmolRGPT achieves competitive results on challenging warehouse spatial reasoning benchmarks, matching or exceeding the performance of much larger alternatives. These findings highlight the potential for efficient, deployable multimodal intelligence in real-world settings without sacrificing core spatial reasoning capabilities. The code of the experimentation will be available at: https://github.com/abtraore/SmolRGPT

Multiple technologies that measure expression levels of protein mixtures in the human body offer a potential for detection and understanding the disease. The recent increase of these technologies prompts researchers to evaluate the individual and combined utility of data generated by the technologies. In this work, we study two data sources to measure the expression of protein mixtures in the human body: whole-sample MS profiling and multiplexed protein arrays. We investigate the individual and combined utility of these technologies by learning and testing a variety of classification models on the data from a pancreatic cancer study. We show that for the combination of these two (heterogeneous) datasets, classification models that work well on one of them individually fail on the combination of the two datasets. We study and propose a class of model fusion methods that acknowledge the differences and try to reap most of the benefits from their combination.

Large Multimodal Models (LMMs) have achieved strong performance across a range of vision and language tasks. However, their spatial reasoning capabilities are under-investigated. In this paper, we construct a novel VQA dataset, Spatial-MM, to comprehensively study LMMs' spatial understanding and reasoning capabilities. Our analyses on object-relationship and multi-hop reasoning reveal several important findings. Firstly, bounding boxes and scene graphs, even synthetic ones, can significantly enhance LMMs' spatial reasoning. Secondly, LMMs struggle more with questions posed from the human perspective than the camera perspective about the image. Thirdly, chain of thought (CoT) prompting does not improve model performance on complex multi-hop questions involving spatial relations. % Moreover, spatial reasoning steps are much less accurate than non-spatial ones across MLLMs. Lastly, our perturbation analysis on GQA-spatial reveals that LMMs are much stronger at basic object detection than complex spatial reasoning. We believe our benchmark dataset and in-depth analyses can spark further research on LMMs spatial reasoning. Spatial-MM benchmark is available at: https://github.com/FatemehShiri/Spatial-MM

Video spatial reasoning is essential for navigation-oriented perception and long-video question answering, where models must infer spatial relations across long horizons under changing viewpoints. However, existing multimodal large language models (MLLMs) remain largely semantic-centric, and often fail to reliably aggregate consistent spatial evidence from redundant video observations, leading to inefficient or unstable reasoning. To address these issues, we propose ConsiSpace, a geometry-consistency-aware framework for geometry-sensitive video spatial reasoning that turns spatial consistency into both an evidence organization principle and an explicit post-SFT learning signal. We build a geometry-consistent memory (GCM) including implicit evidence tokens and explicit geometric cues, and leverage efficient organization strategies to compactly preserve task-related spatial evidence. Furthermore, we utilize unified consistency self-supervised reinforcement learning (UC-SSRL) after supervised fine-tuning to improve cross-view stability, with answer-, metric-, and topology-consistency rewards. Extensive experiments on three spatial-reasoning benchmarks, VSI-Bench, OSI-Bench, and MMSI-Video-Bench, show consistent gains, improving the average score by 12.6 points over the strongest baselines.

We consider molecule generation in 3D space using language models (LMs), which requires discrete tokenization of 3D molecular geometries. Although tokenization of molecular graphs exists, that for 3D geometries is largely unexplored. Here, we attempt to bridge this gap by proposing the Geo2Seq, which converts molecular geometries into SE(3)-invariant 1D discrete sequences. Geo2Seq consists of canonical labeling and invariant spherical representation steps, which together maintain geometric and atomic fidelity in a format conducive to LMs. Our experiments show that, when coupled with Geo2Seq, various LMs excel in molecular geometry generation, especially in controlled generation tasks.

Spatial reasoning remains a persistent challenge for multimodal large language models (MLLMs). Existing approaches largely rely on large-scale, statically curated datasets, where all training samples are treated uniformly regardless of the model's evolving capabilities. This static paradigm is inherently data-inefficient: training capacity is often spent on samples that are either trivial or overly difficult for the model at its current stage. To address this limitation, we propose Ouroboros-Spatial, a self-evolving training framework in which the model plays dual roles as a proposer and a solver. In each iteration, a frozen proposer generates spatial question-answer (QA) pairs from 3D scene metadata and raw video frames, together with executable code for deriving reliable ground truth. A learnable solver is then fine-tuned on the accepted samples, and its per-sample prediction confidence is used as a difficulty signal. This signal is fed back to the proposer in the next iteration, guiding it to generate questions better matched to the solver's current capabilities. Through this closed-loop design, the training distribution co-evolves with model ability, reducing redundant trivial examples while filtering out ambiguous or uninformative samples with limited learning value. Across six spatial reasoning benchmarks, Ouroboros-Spatial substantially improves Qwen3-VL-4B and Qwen3-VL-8B while using an order of magnitude fewer training examples than recent large-scale curated datasets. On VSI-Bench, it yields absolute gains of 9.9 and 6.8 points for the 4B and 8B models, respectively, enabling both to outperform a wide range of strong open-source and proprietary baselines.

Spatial understanding is essential for Multimodal Large Language Models (MLLMs) to support perception, reasoning, and planning in embodied environments. Despite recent progress, existing studies reveal that MLLMs still struggle with spatial understanding. However, existing research lacks a comprehensive and systematic evaluation of these limitations, often restricted to isolated scenarios, such as single-view or video. In this work, we present a systematic analysis of spatial understanding from both data and architectural perspectives across three representative scenarios: single-view, multi-view, and video. We propose a benchmark named MulSeT (Multi-view Spatial Understanding Tasks), and design a series of experiments to analyze the spatial reasoning capabilities of MLLMs. From the data perspective, the performance of spatial understanding converges quickly as the training data increases, and the upper bound is relatively low, especially for tasks that require spatial imagination. This indicates that merely expanding training data is insufficient to achieve satisfactory performance. From the architectural perspective, we find that spatial understanding relies more heavily on the positional encoding within the visual encoder than within the language model, in both cascaded and native MLLMs. Moreover, we explore reasoning injection and envision future improvements through architectural design to optimize spatial understanding. These insights shed light on the limitations of current MLLMs and suggest new directions for improving spatial reasoning capabilities through data scaling and architectural tuning.

Genuine spatial reasoning relies on the capacity to construct and manipulate coherent internal spatial representations, often conceptualized as mental models, rather than merely processing surface linguistic associations. While large language models exhibit advanced capabilities across various domains, existing benchmarks fail to isolate this intrinsic spatial cognition from statistical language heuristics. Furthermore, multimodal evaluations frequently conflate genuine spatial reasoning with visual perception. To systematically investigate whether models construct flexible spatial mental models, we introduce SpatialText, a theory-driven diagnostic framework. Rather than functioning simply as a dataset, SpatialText isolates text-based spatial reasoning through a dual-source methodology. It integrates human-annotated descriptions of real 3D indoor environments, which capture natural ambiguities, perspective shifts, and functional relations, with code-generated, logically precise scenes designed to probe formal spatial deduction and epistemic boundaries. Systematic evaluation across state-of-the-art models reveals fundamental representational limitations. Although models demonstrate proficiency in retrieving explicit spatial facts and operating within global, allocentric coordinate systems, they exhibit critical failures in egocentric perspective transformation and local reference frame reasoning. These systematic errors provide strong evidence that current models rely heavily on linguistic co-occurrence heuristics rather than constructing coherent, verifiable internal spatial representations. SpatialText thus serves as a rigorous instrument for diagnosing the cognitive boundaries of artificial spatial intelligence.

Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E), a U-Net-inspired architecture that integrates state-of-the-art ViT foundation models as encoders to predict mIF signals from H&E images. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available ORION dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on two independent datasets. MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.88 for Pan-CK, 0.57 for CD3e, 0.56 for SMA, 0.36 for CD68, and 0.30 for CD20, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that our model effectively captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.

The development of data-dependent heuristics and representations for biological sequences that reflect their evolutionary distance is critical for large-scale biological research. However, popular machine learning approaches, based on continuous Euclidean spaces, have struggled with the discrete combinatorial formulation of the edit distance that models evolution and the hierarchical relationship that characterises real-world datasets. We present Neural Distance Embeddings (NeuroSEED), a general framework to embed sequences in geometric vector spaces, and illustrate the effectiveness of the hyperbolic space that captures the hierarchical structure and provides an average 22% reduction in embedding RMSE against the best competing geometry. The capacity of the framework and the significance of these improvements are then demonstrated devising supervised and unsupervised NeuroSEED approaches to multiple core tasks in bioinformatics. Benchmarked with common baselines, the proposed approaches display significant accuracy and/or runtime improvements on real-world datasets. As an example for hierarchical clustering, the proposed pretrained and from-scratch methods match the quality of competing baselines with 30x and 15x runtime reduction, respectively.

This paper proposes a question-answering (QA) benchmark for spatial reasoning on natural language text which contains more realistic spatial phenomena not covered by prior work and is challenging for state-of-the-art language models (LM). We propose a distant supervision method to improve on this task. Specifically, we design grammar and reasoning rules to automatically generate a spatial description of visual scenes and corresponding QA pairs. Experiments show that further pretraining LMs on these automatically generated data significantly improves LMs' capability on spatial understanding, which in turn helps to better solve two external datasets, bAbI, and boolQ. We hope that this work can foster investigations into more sophisticated models for spatial reasoning over text.

Spatial reasoning from egocentric videos is inherently challenging because the observable evidence is constrained by the camera trajectory. Existing methods rely on single-turn inference, forcing models to resolve geometric ambiguity through semantic priors rather than verifiable evidence. We argue that spatial reasoning should be revisitable: conclusions formed under limited evidence should remain open to revision when complementary viewpoints become available. Building on this insight, we propose Reason, then Re-reason (ReRe), a training-free, inference-time framework with two phases: in the Reason Phase, an MLLM forms a spatial hypothesis from the original video; in the Re-reason Phase, it verifies or revises the hypothesis by observing a synthesized novel-view video. To enable effective cross-view revisiting, we design a Geometry-to-Video pipeline that renders strategically complementary novel views from predicted 3D geometry. These views feature an elevated, oblique perspective with scene-spanning coverage, while preserving the MLLM's native video interface without architectural modifications. Extensive evaluations on VSI-Bench and STI-Bench demonstrate that ReRe substantially boosts open-source MLLMs to rival proprietary state-of-the-art performance. Project page: https://zhenjiemao.github.io/ReRe/

Nonrigid registration is conventionally divided into point set registration, which aligns sparse geometries, and image registration, which aligns continuous intensity fields on regular grids. However, this dichotomy creates a critical bottleneck for emerging scientific data, such as spatial transcriptomics, where high-dimensional vector-valued functions, e.g., gene expression, are defined on irregular, sparse manifolds. Consequently, researchers currently face a forced choice: either sacrifice single-cell resolution via voxelization to utilize image-based tools, or ignore the critical functional signal to utilize geometric tools. To resolve this dilemma, we propose Domain Elastic Transform (DET), a grid-free probabilistic framework that unifies geometric and functional alignment. By treating data as functions on irregular domains, DET registers high-dimensional signals directly without binning. We formulate the problem within a rigorous Bayesian framework, modeling domain deformation as an elastic motion guided by a joint spatial-functional likelihood. The method is fully unsupervised and scalable, utilizing feature-sensitive downsampling to handle massive atlases. We demonstrate that DET achieves 92\% topological preservation on MERFISH data where state-of-the-art optimal transport methods struggle (<5\%), and successfully registers whole-embryo Stereo-seq atlases across developmental stages -- a task involving massive scale and complex nonrigid growth. The implementation of DET is available on {https://github.com/ohirose/bcpd} (since Mar, 2025).

Spatial reasoning is an essential problem in embodied AI research. Efforts to enhance spatial reasoning abilities through supplementary spatial data and fine-tuning have proven limited and ineffective when addressing complex embodied tasks, largely due to their dependence on language-based outputs. While some approaches have introduced a point-based action space to mitigate this issue, they fall short in managing more intricate tasks within complex environments. This deficiency arises from their failure to fully exploit the inherent thinking and reasoning capabilities that are fundamental strengths of Vision-Language Models (VLMs). To address these limitations, we propose a novel approach named SpatialCoT, specifically designed to bolster the spatial reasoning capabilities of VLMs. Our approach comprises two stages: spatial coordinate bi-directional alignment, which aligns vision-language inputs with spatial coordinates, and chain-of-thought spatial grounding, which harnesses the reasoning capabilities of language models for advanced spatial reasoning. We evaluate SpatialCoT on challenging navigation and manipulation tasks, both in simulation and real-world settings. Experimental results demonstrate that our method significantly outperforms previous state-of-the-art approaches in both tasks.