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Aug 20

HAMIL: Hierarchical Aggregation-Based Multi-Instance Learning for Microscopy Image Classification

Multi-instance learning is common for computer vision tasks, especially in biomedical image processing. Traditional methods for multi-instance learning focus on designing feature aggregation methods and multi-instance classifiers, where the aggregation operation is performed either in feature extraction or learning phase. As deep neural networks (DNNs) achieve great success in image processing via automatic feature learning, certain feature aggregation mechanisms need to be incorporated into common DNN architecture for multi-instance learning. Moreover, flexibility and reliability are crucial considerations to deal with varying quality and number of instances. In this study, we propose a hierarchical aggregation network for multi-instance learning, called HAMIL. The hierarchical aggregation protocol enables feature fusion in a defined order, and the simple convolutional aggregation units lead to an efficient and flexible architecture. We assess the model performance on two microscopy image classification tasks, namely protein subcellular localization using immunofluorescence images and gene annotation using spatial gene expression images. The experimental results show that HAMIL outperforms the state-of-the-art feature aggregation methods and the existing models for addressing these two tasks. The visualization analyses also demonstrate the ability of HAMIL to focus on high-quality instances.

  • 4 authors
·
Mar 16, 2021

Gene-DML: Dual-Pathway Multi-Level Discrimination for Gene Expression Prediction from Histopathology Images

Accurately predicting gene expression from histopathology images offers a scalable and non-invasive approach to molecular profiling, with significant implications for precision medicine and computational pathology. However, existing methods often underutilize the cross-modal representation alignment between histopathology images and gene expression profiles across multiple representational levels, thereby limiting their prediction performance. To address this, we propose Gene-DML, a unified framework that structures latent space through Dual-pathway Multi-Level discrimination to enhance correspondence between morphological and transcriptional modalities. The multi-scale instance-level discrimination pathway aligns hierarchical histopathology representations extracted at local, neighbor, and global levels with gene expression profiles, capturing scale-aware morphological-transcriptional relationships. In parallel, the cross-level instance-group discrimination pathway enforces structural consistency between individual (image/gene) instances and modality-crossed (gene/image, respectively) groups, strengthening the alignment across modalities. By jointly modelling fine-grained and structural-level discrimination, Gene-DML is able to learn robust cross-modal representations, enhancing both predictive accuracy and generalization across diverse biological contexts. Extensive experiments on public spatial transcriptomics datasets demonstrate that Gene-DML achieves state-of-the-art performance in gene expression prediction. The code and checkpoints will be released soon.

  • 4 authors
·
Jul 19, 2025

A Large-Scale Benchmark of Cross-Modal Learning for Histology and Gene Expression in Spatial Transcriptomics

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

  • 9 authors
·
Aug 2, 2025

SPATIA: Multimodal Generation and Prediction of Spatial Cell Phenotypes

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%.

  • 8 authors
·
Jun 14

ST-Align: A Multimodal Foundation Model for Image-Gene Alignment in Spatial Transcriptomics

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.

  • 8 authors
·
Nov 25, 2024

Towards Spatial Transcriptomics-driven Pathology Foundation Models

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.

  • 9 authors
·
Feb 15

HiPoNet: A Multi-View Simplicial Complex Network for High Dimensional Point-Cloud and Single-Cell Data

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.

  • 10 authors
·
Feb 11, 2025

Getting it Right: Improving Spatial Consistency in Text-to-Image Models

One of the key shortcomings in current text-to-image (T2I) models is their inability to consistently generate images which faithfully follow the spatial relationships specified in the text prompt. In this paper, we offer a comprehensive investigation of this limitation, while also developing datasets and methods that achieve state-of-the-art performance. First, we find that current vision-language datasets do not represent spatial relationships well enough; to alleviate this bottleneck, we create SPRIGHT, the first spatially-focused, large scale dataset, by re-captioning 6 million images from 4 widely used vision datasets. Through a 3-fold evaluation and analysis pipeline, we find that SPRIGHT largely improves upon existing datasets in capturing spatial relationships. To demonstrate its efficacy, we leverage only ~0.25% of SPRIGHT and achieve a 22% improvement in generating spatially accurate images while also improving the FID and CMMD scores. Secondly, we find that training on images containing a large number of objects results in substantial improvements in spatial consistency. Notably, we attain state-of-the-art on T2I-CompBench with a spatial score of 0.2133, by fine-tuning on <500 images. Finally, through a set of controlled experiments and ablations, we document multiple findings that we believe will enhance the understanding of factors that affect spatial consistency in text-to-image models. We publicly release our dataset and model to foster further research in this area.

  • 11 authors
·
Apr 1, 2024 3

ViTally Consistent: Scaling Biological Representation Learning for Cell Microscopy

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations. In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens. We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological data.

  • 13 authors
·
Nov 4, 2024

hist2RNA: An efficient deep learning architecture to predict gene expression from breast cancer histopathology images

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12-3.06), p < 5 x 10-3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.85 (95% CI 1.30-2.68), p < 5 x 10-3).

  • 6 authors
·
Apr 10, 2023

Domain Elastic Transform: Bayesian Function Registration for High-Dimensional Scientific Data

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).

  • 2 authors
·
Mar 21

Learned representation-guided diffusion models for large-image generation

To synthesize high-fidelity samples, diffusion models typically require auxiliary data to guide the generation process. However, it is impractical to procure the painstaking patch-level annotation effort required in specialized domains like histopathology and satellite imagery; it is often performed by domain experts and involves hundreds of millions of patches. Modern-day self-supervised learning (SSL) representations encode rich semantic and visual information. In this paper, we posit that such representations are expressive enough to act as proxies to fine-grained human labels. We introduce a novel approach that trains diffusion models conditioned on embeddings from SSL. Our diffusion models successfully project these features back to high-quality histopathology and remote sensing images. In addition, we construct larger images by assembling spatially consistent patches inferred from SSL embeddings, preserving long-range dependencies. Augmenting real data by generating variations of real images improves downstream classifier accuracy for patch-level and larger, image-scale classification tasks. Our models are effective even on datasets not encountered during training, demonstrating their robustness and generalizability. Generating images from learned embeddings is agnostic to the source of the embeddings. The SSL embeddings used to generate a large image can either be extracted from a reference image, or sampled from an auxiliary model conditioned on any related modality (e.g. class labels, text, genomic data). As proof of concept, we introduce the text-to-large image synthesis paradigm where we successfully synthesize large pathology and satellite images out of text descriptions.

  • 7 authors
·
Dec 12, 2023

CodeCytos: AI-assisted spatial molecular imaging analysis via code-augmented agent action space

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.

Complex Mathematical Expression Recognition: Benchmark, Large-Scale Dataset and Strong Baseline

Mathematical Expression Recognition (MER) has made significant progress in recognizing simple expressions, but the robust recognition of complex mathematical expressions with many tokens and multiple lines remains a formidable challenge. In this paper, we first introduce CMER-Bench, a carefully constructed benchmark that categorizes expressions into three difficulty levels: easy, moderate, and complex. Leveraging CMER-Bench, we conduct a comprehensive evaluation of existing MER models and general-purpose multimodal large language models (MLLMs). The results reveal that while current methods perform well on easy and moderate expressions, their performance degrades significantly when handling complex mathematical expressions, mainly because existing public training datasets are primarily composed of simple samples. In response, we propose MER-17M and CMER-3M that are large-scale datasets emphasizing the recognition of complex mathematical expressions. The datasets provide rich and diverse samples to support the development of accurate and robust complex MER models. Furthermore, to address the challenges posed by the complicated spatial layout of complex expressions, we introduce a novel expression tokenizer, and a new representation called Structured Mathematical Language, which explicitly models the hierarchical and spatial structure of expressions beyond LaTeX format. Based on these, we propose a specialized model named CMERNet, built upon an encoder-decoder architecture and trained on CMER-3M. Experimental results show that CMERNet, with only 125 million parameters, significantly outperforms existing MER models and MLLMs on CMER-Bench.

  • 5 authors
·
Dec 14, 2025

PixCell: A generative foundation model for digital histopathology images

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

A Foundation Model for Spatial Proteomics

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.

  • 60 authors
·
Jun 2, 2025

CoMPaSS: Enhancing Spatial Understanding in Text-to-Image Diffusion Models

Text-to-image diffusion models excel at generating photorealistic images, but commonly struggle to render accurate spatial relationships described in text prompts. We identify two core issues underlying this common failure: 1) the ambiguous nature of spatial-related data in existing datasets, and 2) the inability of current text encoders to accurately interpret the spatial semantics of input descriptions. We address these issues with CoMPaSS, a versatile training framework that enhances spatial understanding of any T2I diffusion model. CoMPaSS solves the ambiguity of spatial-related data with the Spatial Constraints-Oriented Pairing (SCOP) data engine, which curates spatially-accurate training data through a set of principled spatial constraints. To better exploit the curated high-quality spatial priors, CoMPaSS further introduces a Token ENcoding ORdering (TENOR) module to allow better exploitation of high-quality spatial priors, effectively compensating for the shortcoming of text encoders. Extensive experiments on four popular open-weight T2I diffusion models covering both UNet- and MMDiT-based architectures demonstrate the effectiveness of CoMPaSS by setting new state-of-the-arts with substantial relative gains across well-known benchmarks on spatial relationships generation, including VISOR (+98%), T2I-CompBench Spatial (+67%), and GenEval Position (+131%). Code will be available at https://github.com/blurgyy/CoMPaSS.

  • 8 authors
·
Dec 17, 2024

Presenting an extensive lab- and field-image dataset of crops and weeds for computer vision tasks in agriculture

We present two large datasets of labelled plant-images that are suited towards the training of machine learning and computer vision models. The first dataset encompasses as the day of writing over 1.2 million images of indoor-grown crops and weeds common to the Canadian Prairies and many US states. The second dataset consists of over 540,000 images of plants imaged in farmland. All indoor plant images are labelled by species and we provide rich etadata on the level of individual images. This comprehensive database allows to filter the datasets under user-defined specifications such as for example the crop-type or the age of the plant. Furthermore, the indoor dataset contains images of plants taken from a wide variety of angles, including profile shots, top-down shots, and angled perspectives. The images taken from plants in fields are all from a top-down perspective and contain usually multiple plants per image. For these images metadata is also available. In this paper we describe both datasets' characteristics with respect to plant variety, plant age, and number of images. We further introduce an open-access sample of the indoor-dataset that contains 1,000 images of each species covered in our dataset. These, in total 14,000 images, had been selected, such that they form a representative sample with respect to plant age and ndividual plants per species. This sample serves as a quick entry point for new users to the dataset, allowing them to explore the data on a small scale and find the parameters of data most useful for their application without having to deal with hundreds of thousands of individual images.

  • 6 authors
·
Aug 12, 2021

Extending Sequence Length is Not All You Need: Effective Integration of Multimodal Signals for Gene Expression Prediction

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.

  • 6 authors
·
Feb 24

Fine-Tuning and Training of DenseNet for Histopathology Image Representation Using TCGA Diagnostic Slides

Feature vectors provided by pre-trained deep artificial neural networks have become a dominant source for image representation in recent literature. Their contribution to the performance of image analysis can be improved through finetuning. As an ultimate solution, one might even train a deep network from scratch with the domain-relevant images, a highly desirable option which is generally impeded in pathology by lack of labeled images and the computational expense. In this study, we propose a new network, namely KimiaNet, that employs the topology of the DenseNet with four dense blocks, fine-tuned and trained with histopathology images in different configurations. We used more than 240,000 image patches with 1000x1000 pixels acquired at 20x magnification through our proposed "highcellularity mosaic" approach to enable the usage of weak labels of 7,126 whole slide images of formalin-fixed paraffin-embedded human pathology samples publicly available through the The Cancer Genome Atlas (TCGA) repository. We tested KimiaNet using three public datasets, namely TCGA, endometrial cancer images, and colorectal cancer images by evaluating the performance of search and classification when corresponding features of different networks are used for image representation. As well, we designed and trained multiple convolutional batch-normalized ReLU (CBR) networks. The results show that KimiaNet provides superior results compared to the original DenseNet and smaller CBR networks when used as feature extractor to represent histopathology images.

  • 22 authors
·
Jan 19, 2021

Semantic and Visual Crop-Guided Diffusion Models for Heterogeneous Tissue Synthesis in Histopathology

Synthetic data generation in histopathology faces unique challenges: preserving tissue heterogeneity, capturing subtle morphological features, and scaling to unannotated datasets. We present a latent diffusion model that generates realistic heterogeneous histopathology images through a novel dual-conditioning approach combining semantic segmentation maps with tissue-specific visual crops. Unlike existing methods that rely on text prompts or abstract visual embeddings, our approach preserves critical morphological details by directly incorporating raw tissue crops from corresponding semantic regions. For annotated datasets (i.e., Camelyon16, Panda), we extract patches ensuring 20-80% tissue heterogeneity. For unannotated data (i.e., TCGA), we introduce a self-supervised extension that clusters whole-slide images into 100 tissue types using foundation model embeddings, automatically generating pseudo-semantic maps for training. Our method synthesizes high-fidelity images with precise region-wise annotations, achieving superior performance on downstream segmentation tasks. When evaluated on annotated datasets, models trained on our synthetic data show competitive performance to those trained on real data, demonstrating the utility of controlled heterogeneous tissue generation. In quantitative evaluation, prompt-guided synthesis reduces Frechet Distance by up to 6X on Camelyon16 (from 430.1 to 72.0) and yields 2-3x lower FD across Panda and TCGA. Downstream DeepLabv3+ models trained solely on synthetic data attain test IoU of 0.71 and 0.95 on Camelyon16 and Panda, within 1-2% of real-data baselines (0.72 and 0.96). By scaling to 11,765 TCGA whole-slide images without manual annotations, our framework offers a practical solution for an urgent need for generating diverse, annotated histopathology data, addressing a critical bottleneck in computational pathology.

  • 5 authors
·
Sep 30, 2025

Mixed Magnification Aggregation for Generalizable Region-Level Representations in Computational Pathology

In recent years, a standard computational pathology workflow has emerged where whole slide images are cropped into tiles, these tiles are processed using a foundation model, and task-specific models are built using the resulting representations. At least 15 different foundation models have been proposed, and the vast majority are trained exclusively with tiles using the 20times magnification. However, it is well known that certain histologic features can only be discerned with larger context windows and requires a pathologist to zoom in and out when analyzing a whole slide image. Furthermore, creating 224times224 pixel crops at 20times leads to a large number of tiles per slide, which can be gigapixel in size. To more accurately capture multi-resolution features and investigate the possibility of reducing the number of representations per slide, we propose a region-level mixing encoder. Our approach jointly fuses image tile representations of a mixed magnification foundation model using a masked embedding modeling pretraining step. We explore a design space for pretraining the proposed mixed-magnification region aggregators and evaluate our models on transfer to biomarker prediction tasks representing various cancer types. Results demonstrate cancer dependent improvements in predictive performance, highlighting the importance of spatial context and understanding.

  • 10 authors
·
Feb 24

Polyp-Gen: Realistic and Diverse Polyp Image Generation for Endoscopic Dataset Expansion

Automated diagnostic systems (ADS) have shown significant potential in the early detection of polyps during endoscopic examinations, thereby reducing the incidence of colorectal cancer. However, due to high annotation costs and strict privacy concerns, acquiring high-quality endoscopic images poses a considerable challenge in the development of ADS. Despite recent advancements in generating synthetic images for dataset expansion, existing endoscopic image generation algorithms failed to accurately generate the details of polyp boundary regions and typically required medical priors to specify plausible locations and shapes of polyps, which limited the realism and diversity of the generated images. To address these limitations, we present Polyp-Gen, the first full-automatic diffusion-based endoscopic image generation framework. Specifically, we devise a spatial-aware diffusion training scheme with a lesion-guided loss to enhance the structural context of polyp boundary regions. Moreover, to capture medical priors for the localization of potential polyp areas, we introduce a hierarchical retrieval-based sampling strategy to match similar fine-grained spatial features. In this way, our Polyp-Gen can generate realistic and diverse endoscopic images for building reliable ADS. Extensive experiments demonstrate the state-of-the-art generation quality, and the synthetic images can improve the downstream polyp detection task. Additionally, our Polyp-Gen has shown remarkable zero-shot generalizability on other datasets. The source code is available at https://github.com/CUHK-AIM-Group/Polyp-Gen.

  • 7 authors
·
Jan 27, 2025

Generalized Referring Expression Segmentation on Aerial Photos

Referring expression segmentation is a fundamental task in computer vision that integrates natural language understanding with precise visual localization of target regions. Considering aerial imagery (e.g., modern aerial photos collected through drones, historical photos from aerial archives, high-resolution satellite imagery, etc.) presents unique challenges because spatial resolution varies widely across datasets, the use of color is not consistent, targets often shrink to only a few pixels, and scenes contain very high object densities and objects with partial occlusions. This work presents Aerial-D, a new large-scale referring expression segmentation dataset for aerial imagery, comprising 37,288 images with 1,522,523 referring expressions that cover 259,709 annotated targets, spanning across individual object instances, groups of instances, and semantic regions covering 21 distinct classes that range from vehicles and infrastructure to land coverage types. The dataset was constructed through a fully automatic pipeline that combines systematic rule-based expression generation with a Large Language Model (LLM) enhancement procedure that enriched both the linguistic variety and the focus on visual details within the referring expressions. Filters were additionally used to simulate historic imaging conditions for each scene. We adopted the RSRefSeg architecture, and trained models on Aerial-D together with prior aerial datasets, yielding unified instance and semantic segmentation from text for both modern and historical images. Results show that the combined training achieves competitive performance on contemporary benchmarks, while maintaining strong accuracy under monochrome, sepia, and grainy degradations that appear in archival aerial photography. The dataset, trained models, and complete software pipeline are publicly available at https://luispl77.github.io/aerial-d .

inesc-id INESC-ID Lisboa
·
Dec 8, 2025

MIRROR: Multi-Modal Pathological Self-Supervised Representation Learning via Modality Alignment and Retention

Histopathology and transcriptomics are fundamental modalities in oncology, encapsulating the morphological and molecular aspects of the disease. Multi-modal self-supervised learning has demonstrated remarkable potential in learning pathological representations by integrating diverse data sources. Conventional multi-modal integration methods primarily emphasize modality alignment, while paying insufficient attention to retaining the modality-specific structures. However, unlike conventional scenarios where multi-modal inputs share highly overlapping features, histopathology and transcriptomics exhibit pronounced heterogeneity, offering orthogonal yet complementary insights. Histopathology provides morphological and spatial context, elucidating tissue architecture and cellular topology, whereas transcriptomics delineates molecular signatures through gene expression patterns. This inherent disparity introduces a major challenge in aligning them while maintaining modality-specific fidelity. To address these challenges, we present MIRROR, a novel multi-modal representation learning method designed to foster both modality alignment and retention. MIRROR employs dedicated encoders to extract comprehensive features for each modality, which is further complemented by a modality alignment module to achieve seamless integration between phenotype patterns and molecular profiles. Furthermore, a modality retention module safeguards unique attributes from each modality, while a style clustering module mitigates redundancy and enhances disease-relevant information by modeling and aligning consistent pathological signatures within a clustering space. Extensive evaluations on TCGA cohorts for cancer subtyping and survival analysis highlight MIRROR's superior performance, demonstrating its effectiveness in constructing comprehensive oncological feature representations and benefiting the cancer diagnosis.

  • 7 authors
·
Mar 1, 2025

Linking spatial biology and clinical histology via Haiku

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.

SpaText: Spatio-Textual Representation for Controllable Image Generation

Recent text-to-image diffusion models are able to generate convincing results of unprecedented quality. However, it is nearly impossible to control the shapes of different regions/objects or their layout in a fine-grained fashion. Previous attempts to provide such controls were hindered by their reliance on a fixed set of labels. To this end, we present SpaText - a new method for text-to-image generation using open-vocabulary scene control. In addition to a global text prompt that describes the entire scene, the user provides a segmentation map where each region of interest is annotated by a free-form natural language description. Due to lack of large-scale datasets that have a detailed textual description for each region in the image, we choose to leverage the current large-scale text-to-image datasets and base our approach on a novel CLIP-based spatio-textual representation, and show its effectiveness on two state-of-the-art diffusion models: pixel-based and latent-based. In addition, we show how to extend the classifier-free guidance method in diffusion models to the multi-conditional case and present an alternative accelerated inference algorithm. Finally, we offer several automatic evaluation metrics and use them, in addition to FID scores and a user study, to evaluate our method and show that it achieves state-of-the-art results on image generation with free-form textual scene control.

  • 9 authors
·
Nov 25, 2022

CellCLIP -- Learning Perturbation Effects in Cell Painting via Text-Guided Contrastive Learning

High-content screening (HCS) assays based on high-throughput microscopy techniques such as Cell Painting have enabled the interrogation of cells' morphological responses to perturbations at an unprecedented scale. The collection of such data promises to facilitate a better understanding of the relationships between different perturbations and their effects on cellular state. Towards achieving this goal, recent advances in cross-modal contrastive learning could, in theory, be leveraged to learn a unified latent space that aligns perturbations with their corresponding morphological effects. However, the application of such methods to HCS data is not straightforward due to substantial differences in the semantics of Cell Painting images compared to natural images, and the difficulty of representing different classes of perturbations (e.g., small molecule vs CRISPR gene knockout) in a single latent space. In response to these challenges, here we introduce CellCLIP, a cross-modal contrastive learning framework for HCS data. CellCLIP leverages pre-trained image encoders coupled with a novel channel encoding scheme to better capture relationships between different microscopy channels in image embeddings, along with natural language encoders for representing perturbations. Our framework outperforms current open-source models, demonstrating the best performance in both cross-modal retrieval and biologically meaningful downstream tasks while also achieving significant reductions in computation time.

  • 4 authors
·
May 16, 2025

Towards Open-Ended Visual Scientific Discovery with Sparse Autoencoders

Scientific archives now contain hundreds of petabytes of data across genomics, ecology, climate, and molecular biology that could reveal undiscovered patterns if systematically analyzed at scale. Large-scale, weakly-supervised datasets in language and vision have driven the development of foundation models whose internal representations encode structure (patterns, co-occurrences and statistical regularities) beyond their training objectives. Most existing methods extract structure only for pre-specified targets; they excel at confirmation but do not support open-ended discovery of unknown patterns. We ask whether sparse autoencoders (SAEs) can enable open-ended feature discovery from foundation model representations. We evaluate this question in controlled rediscovery studies, where the learned SAE features are tested for alignment with semantic concepts on a standard segmentation benchmark and compared against strong label-free alternatives on concept-alignment metrics. Applied to ecological imagery, the same procedure surfaces fine-grained anatomical structure without access to segmentation or part labels, providing a scientific case study with ground-truth validation. While our experiments focus on vision with an ecology case study, the method is domain-agnostic and applicable to models in other sciences (e.g., proteins, genomics, weather). Our results indicate that sparse decomposition provides a practical instrument for exploring what scientific foundation models have learned, an important prerequisite for moving from confirmation to genuine discovery.

  • 4 authors
·
Nov 21, 2025

Integrating Biological Knowledge for Robust Microscopy Image Profiling on De Novo Cell Lines

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

  • 4 authors
·
Jul 14, 2025

Everything in Its Place: Benchmarking Spatial Intelligence of Text-to-Image Models

Text-to-image (T2I) models have achieved remarkable success in generating high-fidelity images, but they often fail in handling complex spatial relationships, e.g., spatial perception, reasoning, or interaction. These critical aspects are largely overlooked by current benchmarks due to their short or information-sparse prompt design. In this paper, we introduce SpatialGenEval, a new benchmark designed to systematically evaluate the spatial intelligence of T2I models, covering two key aspects: (1) SpatialGenEval involves 1,230 long, information-dense prompts across 25 real-world scenes. Each prompt integrates 10 spatial sub-domains and corresponding 10 multi-choice question-answer pairs, ranging from object position and layout to occlusion and causality. Our extensive evaluation of 21 state-of-the-art models reveals that higher-order spatial reasoning remains a primary bottleneck. (2) To demonstrate that the utility of our information-dense design goes beyond simple evaluation, we also construct the SpatialT2I dataset. It contains 15,400 text-image pairs with rewritten prompts to ensure image consistency while preserving information density. Fine-tuned results on current foundation models (i.e., Stable Diffusion-XL, Uniworld-V1, OmniGen2) yield consistent performance gains (+4.2%, +5.7%, +4.4%) and more realistic effects in spatial relations, highlighting a data-centric paradigm to achieve spatial intelligence in T2I models.

AGI-LAB-HF AGI Lab
·
Jan 28 3

ChAda-ViT : Channel Adaptive Attention for Joint Representation Learning of Heterogeneous Microscopy Images

Unlike color photography images, which are consistently encoded into RGB channels, biological images encompass various modalities, where the type of microscopy and the meaning of each channel varies with each experiment. Importantly, the number of channels can range from one to a dozen and their correlation is often comparatively much lower than RGB, as each of them brings specific information content. This aspect is largely overlooked by methods designed out of the bioimage field, and current solutions mostly focus on intra-channel spatial attention, often ignoring the relationship between channels, yet crucial in most biological applications. Importantly, the variable channel type and count prevent the projection of several experiments to a unified representation for large scale pre-training. In this study, we propose ChAda-ViT, a novel Channel Adaptive Vision Transformer architecture employing an Inter-Channel Attention mechanism on images with an arbitrary number, order and type of channels. We also introduce IDRCell100k, a bioimage dataset with a rich set of 79 experiments covering 7 microscope modalities, with a multitude of channel types, and channel counts varying from 1 to 10 per experiment. Our proposed architecture, trained in a self-supervised manner, outperforms existing approaches in several biologically relevant downstream tasks. Additionally, it can be used to bridge the gap for the first time between assays with different microscopes, channel numbers or types by embedding various image and experimental modalities into a unified biological image representation. The latter should facilitate interdisciplinary studies and pave the way for better adoption of deep learning in biological image-based analyses. Code and Data to be released soon.

  • 7 authors
·
Nov 26, 2023

PathAlign: A vision-language model for whole slide images in histopathology

Microscopic interpretation of histopathology images underlies many important diagnostic and treatment decisions. While advances in vision-language modeling raise new opportunities for analysis of such images, the gigapixel-scale size of whole slide images (WSIs) introduces unique challenges. Additionally, pathology reports simultaneously highlight key findings from small regions while also aggregating interpretation across multiple slides, often making it difficult to create robust image-text pairs. As such, pathology reports remain a largely untapped source of supervision in computational pathology, with most efforts relying on region-of-interest annotations or self-supervision at the patch-level. In this work, we develop a vision-language model based on the BLIP-2 framework using WSIs paired with curated text from pathology reports. This enables applications utilizing a shared image-text embedding space, such as text or image retrieval for finding cases of interest, as well as integration of the WSI encoder with a frozen large language model (LLM) for WSI-based generative text capabilities such as report generation or AI-in-the-loop interactions. We utilize a de-identified dataset of over 350,000 WSIs and diagnostic text pairs, spanning a wide range of diagnoses, procedure types, and tissue types. We present pathologist evaluation of text generation and text retrieval using WSI embeddings, as well as results for WSI classification and workflow prioritization (slide-level triaging). Model-generated text for WSIs was rated by pathologists as accurate, without clinically significant error or omission, for 78% of WSIs on average. This work demonstrates exciting potential capabilities for language-aligned WSI embeddings.

  • 17 authors
·
Jun 27, 2024

SpatialMosaic: A Multiview VLM Dataset for Partial Visibility

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.

  • 6 authors
·
Apr 8

Benchmarking Spatial Relationships in Text-to-Image Generation

Spatial understanding is a fundamental aspect of computer vision and integral for human-level reasoning about images, making it an important component for grounded language understanding. While recent text-to-image synthesis (T2I) models have shown unprecedented improvements in photorealism, it is unclear whether they have reliable spatial understanding capabilities. We investigate the ability of T2I models to generate correct spatial relationships among objects and present VISOR, an evaluation metric that captures how accurately the spatial relationship described in text is generated in the image. To benchmark existing models, we introduce a dataset, SR_{2D}, that contains sentences describing two or more objects and the spatial relationships between them. We construct an automated evaluation pipeline to recognize objects and their spatial relationships, and employ it in a large-scale evaluation of T2I models. Our experiments reveal a surprising finding that, although state-of-the-art T2I models exhibit high image quality, they are severely limited in their ability to generate multiple objects or the specified spatial relations between them. Our analyses demonstrate several biases and artifacts of T2I models such as the difficulty with generating multiple objects, a bias towards generating the first object mentioned, spatially inconsistent outputs for equivalent relationships, and a correlation between object co-occurrence and spatial understanding capabilities. We conduct a human study that shows the alignment between VISOR and human judgement about spatial understanding. We offer the SR_{2D} dataset and the VISOR metric to the community in support of T2I reasoning research.

  • 8 authors
·
Dec 20, 2022

Hierarchical Spatial Algorithms for High-Resolution Image Quantization and Feature Extraction

This study introduces a modular framework for spatial image processing, integrating grayscale quantization, color and brightness enhancement, image sharpening, bidirectional transformation pipelines, and geometric feature extraction. A stepwise intensity transformation quantizes grayscale images into eight discrete levels, producing a posterization effect that simplifies representation while preserving structural detail. Color enhancement is achieved via histogram equalization in both RGB and YCrCb color spaces, with the latter improving contrast while maintaining chrominance fidelity. Brightness adjustment is implemented through HSV value-channel manipulation, and image sharpening is performed using a 3 * 3 convolution kernel to enhance high-frequency details. A bidirectional transformation pipeline that integrates unsharp masking, gamma correction, and noise amplification achieved accuracy levels of 76.10% and 74.80% for the forward and reverse processes, respectively. Geometric feature extraction employed Canny edge detection, Hough-based line estimation (e.g., 51.50{\deg} for billiard cue alignment), Harris corner detection, and morphological window localization. Cue isolation further yielded 81.87\% similarity against ground truth images. Experimental evaluation across diverse datasets demonstrates robust and deterministic performance, highlighting its potential for real-time image analysis and computer vision.

  • 1 authors
·
Oct 9, 2025

EXAONE Path 2.5: Pathology Foundation Model with Multi-Omics Alignment

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.

  • 7 authors
·
Dec 15, 2025

Segmentation with Noisy Labels via Spatially Correlated Distributions

In semantic segmentation, the accuracy of models heavily depends on the high-quality annotations. However, in many practical scenarios such as medical imaging and remote sensing, obtaining true annotations is not straightforward and usually requires significant human labor. Relying on human labor often introduces annotation errors, including mislabeling, omissions, and inconsistency between annotators. In the case of remote sensing, differences in procurement time can lead to misaligned ground truth annotations. These label errors are not independently distributed, and instead usually appear in spatially connected regions where adjacent pixels are more likely to share the same errors. To address these issues, we propose an approximate Bayesian estimation based on a probabilistic model that assumes training data includes label errors, incorporating the tendency for these errors to occur with spatial correlations between adjacent pixels. Bayesian inference requires computing the posterior distribution of label errors, which becomes intractable when spatial correlations are present. We represent the correlation of label errors between adjacent pixels through a Gaussian distribution whose covariance is structured by a Kac-Murdock-Szeg\"{o} (KMS) matrix, solving the computational challenges. Through experiments on multiple segmentation tasks, we confirm that leveraging the spatial correlation of label errors significantly improves performance. Notably, in specific tasks such as lung segmentation, the proposed method achieves performance comparable to training with clean labels under moderate noise levels. Code is available at https://github.com/pfnet-research/Bayesian_SpatialCorr.

  • 3 authors
·
Apr 20, 2025

A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

  • 19 authors
·
Jul 22, 2024

ProtoPathway: Biologically Structured Prototype-Pathway Fusion for Multimodal Cancer Survival Prediction

We introduce ProtoPathway, an interpretable-by-design multimodal framework for cancer survival prediction that unifies whole slide imaging and transcriptomics through encoders producing biologically grounded representations on both sides of the fusion. On the histopathology side, K learnable morphological prototypes, trained end-to-end with the survival objective, serve as the slide representation itself: patches flow into prototype tokens via soft assignment, compressing variable-length patch sets into fixed task-adaptive tokens. On the genomic side, a bipartite graph neural network encodes gene expression within the Reactome pathway hierarchy, producing pathway embeddings that reflect both constituent genes and their broader biological context through bidirectional message passing over a shared gene--pathway graph. Cross-modal attention then operates over a compact prototype times pathway matrix in which prototypes query pathways, modeling the biological direction in which molecular programs give rise to tissue morphology. Because both axes carry stable task-learned identity, the attention matrix is itself an interpretability output, yielding native inference-time attribution across the full biological hierarchy, from genes through pathways and prototypes to spatial tissue maps. We evaluate on five TCGA cancer cohorts, demonstrating competitive or superior survival prediction with substantially improved biological interpretability and reduced computational cost, with interpretability claims validated through fold-stratified rank-based population-level analysis. Our source code, model weights, and Reactome pathways, together with a unified codebase reimplementing all multimodal survival baselines under identical preprocessing and evaluation, are available at: https://github.com/AmayaGS/ProtoPathway.

  • 5 authors
·
May 19

MIPHEI-ViT: Multiplex Immunofluorescence Prediction from H&E Images using ViT Foundation Models

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.

  • 5 authors
·
May 15, 2025

Learning Structured Output Representations from Attributes using Deep Conditional Generative Models

Structured output representation is a generative task explored in computer vision that often times requires the mapping of low dimensional features to high dimensional structured outputs. Losses in complex spatial information in deterministic approaches such as Convolutional Neural Networks (CNN) lead to uncertainties and ambiguous structures within a single output representation. A probabilistic approach through deep Conditional Generative Models (CGM) is presented by Sohn et al. in which a particular model known as the Conditional Variational Auto-encoder (CVAE) is introduced and explored. While the original paper focuses on the task of image segmentation, this paper adopts the CVAE framework for the task of controlled output representation through attributes. This approach allows us to learn a disentangled multimodal prior distribution, resulting in more controlled and robust approach to sample generation. In this work we recreate the CVAE architecture and train it on images conditioned on various attributes obtained from two image datasets; the Large-scale CelebFaces Attributes (CelebA) dataset and the Caltech-UCSD Birds (CUB-200-2011) dataset. We attempt to generate new faces with distinct attributes such as hair color and glasses, as well as different bird species samples with various attributes. We further introduce strategies for improving generalized sample generation by applying a weighted term to the variational lower bound.

  • 1 authors
·
Apr 30, 2023

PathGen-1.6M: 1.6 Million Pathology Image-text Pairs Generation through Multi-agent Collaboration

Vision Language Models (VLMs) like CLIP have attracted substantial attention in pathology, serving as backbones for applications such as zero-shot image classification and Whole Slide Image (WSI) analysis. Additionally, they can function as vision encoders when combined with large language models (LLMs) to support broader capabilities. Current efforts to train pathology VLMs rely on pathology image-text pairs from platforms like PubMed, YouTube, and Twitter, which provide limited, unscalable data with generally suboptimal image quality. In this work, we leverage large-scale WSI datasets like TCGA to extract numerous high-quality image patches. We then train a large multimodal model to generate captions for these images, creating PathGen-1.6M, a dataset containing 1.6 million high-quality image-caption pairs. Our approach involves multiple agent models collaborating to extract representative WSI patches, generating and refining captions to obtain high-quality image-text pairs. Extensive experiments show that integrating these generated pairs with existing datasets to train a pathology-specific CLIP model, PathGen-CLIP, significantly enhances its ability to analyze pathological images, with substantial improvements across nine pathology-related zero-shot image classification tasks and three whole-slide image tasks. Furthermore, we construct 200K instruction-tuning data based on PathGen-1.6M and integrate PathGen-CLIP with the Vicuna LLM to create more powerful multimodal models through instruction tuning. Overall, we provide a scalable pathway for high-quality data generation in pathology, paving the way for next-generation general pathology models.

  • 10 authors
·
Jun 28, 2024

OpenSpatial: A Principled Data Engine for Empowering Spatial Intelligence

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.

Generative Distribution Embeddings

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

  • 5 authors
·
May 23, 2025

Binary Latent Diffusion

In this paper, we show that a binary latent space can be explored for compact yet expressive image representations. We model the bi-directional mappings between an image and the corresponding latent binary representation by training an auto-encoder with a Bernoulli encoding distribution. On the one hand, the binary latent space provides a compact discrete image representation of which the distribution can be modeled more efficiently than pixels or continuous latent representations. On the other hand, we now represent each image patch as a binary vector instead of an index of a learned cookbook as in discrete image representations with vector quantization. In this way, we obtain binary latent representations that allow for better image quality and high-resolution image representations without any multi-stage hierarchy in the latent space. In this binary latent space, images can now be generated effectively using a binary latent diffusion model tailored specifically for modeling the prior over the binary image representations. We present both conditional and unconditional image generation experiments with multiple datasets, and show that the proposed method performs comparably to state-of-the-art methods while dramatically improving the sampling efficiency to as few as 16 steps without using any test-time acceleration. The proposed framework can also be seamlessly scaled to 1024 times 1024 high-resolution image generation without resorting to latent hierarchy or multi-stage refinements.

  • 4 authors
·
Apr 10, 2023

Show, Don't Tell: Evaluating Spatial Cognition in Generative Pixels Rather Than LLM Text

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.

OmniAI-ZJU ZJU-OmniAI
·
Jul 22 2

Referring Expression Comprehension: A Survey of Methods and Datasets

Referring expression comprehension (REC) aims to localize a target object in an image described by a referring expression phrased in natural language. Different from the object detection task that queried object labels have been pre-defined, the REC problem only can observe the queries during the test. It thus more challenging than a conventional computer vision problem. This task has attracted a lot of attention from both computer vision and natural language processing community, and several lines of work have been proposed, from CNN-RNN model, modular network to complex graph-based model. In this survey, we first examine the state of the art by comparing modern approaches to the problem. We classify methods by their mechanism to encode the visual and textual modalities. In particular, we examine the common approach of joint embedding images and expressions to a common feature space. We also discuss modular architectures and graph-based models that interface with structured graph representation. In the second part of this survey, we review the datasets available for training and evaluating REC systems. We then group results according to the datasets, backbone models, settings so that they can be fairly compared. Finally, we discuss promising future directions for the field, in particular the compositional referring expression comprehension that requires longer reasoning chain to address.

  • 3 authors
·
Jul 18, 2020

PosFormer: Recognizing Complex Handwritten Mathematical Expression with Position Forest Transformer

Handwritten Mathematical Expression Recognition (HMER) has wide applications in human-machine interaction scenarios, such as digitized education and automated offices. Recently, sequence-based models with encoder-decoder architectures have been commonly adopted to address this task by directly predicting LaTeX sequences of expression images. However, these methods only implicitly learn the syntax rules provided by LaTeX, which may fail to describe the position and hierarchical relationship between symbols due to complex structural relations and diverse handwriting styles. To overcome this challenge, we propose a position forest transformer (PosFormer) for HMER, which jointly optimizes two tasks: expression recognition and position recognition, to explicitly enable position-aware symbol feature representation learning. Specifically, we first design a position forest that models the mathematical expression as a forest structure and parses the relative position relationships between symbols. Without requiring extra annotations, each symbol is assigned a position identifier in the forest to denote its relative spatial position. Second, we propose an implicit attention correction module to accurately capture attention for HMER in the sequence-based decoder architecture. Extensive experiments validate the superiority of PosFormer, which consistently outperforms the state-of-the-art methods 2.03%/1.22%/2.00%, 1.83%, and 4.62% gains on the single-line CROHME 2014/2016/2019, multi-line M2E, and complex MNE datasets, respectively, with no additional latency or computational cost. Code is available at https://github.com/SJTU-DeepVisionLab/PosFormer.

  • 4 authors
·
Jul 10, 2024

ContriMix: Unsupervised disentanglement of content and attribute for domain generalization in microscopy image analysis

Domain generalization is critical for real-world applications of machine learning to microscopy images, including histopathology and fluorescence imaging. Artifacts in these modalities arise through a complex combination of factors relating to tissue collection and laboratory processing, as well as factors intrinsic to patient samples. In fluorescence imaging, these artifacts stem from variations across experimental batches. The complexity and subtlety of these artifacts make the enumeration of data domains intractable. Therefore, augmentation-based methods of domain generalization that require domain identifiers and manual fine-tuning are inadequate in this setting. To overcome this challenge, we introduce ContriMix, a domain generalization technique that learns to generate synthetic images by disentangling and permuting the biological content ("content") and technical variations ("attributes") in microscopy images. ContriMix does not rely on domain identifiers or handcrafted augmentations and makes no assumptions about the input characteristics of images. We assess the performance of ContriMix on two pathology datasets dealing with patch classification and Whole Slide Image label prediction tasks respectively (Camelyon17-WILDS and RCC subtyping), and one fluorescence microscopy dataset (RxRx1-WILDS). Without any access to domain identifiers at train or test time, ContriMix performs similar or better than current state-of-the-art methods in all these datasets, motivating its usage for microscopy image analysis in real-world settings where domain information is hard to come by. The code for ContriMix can be found at https://gitlab.com/huutan86/contrimix

  • 13 authors
·
Jun 7, 2023

Does your model understand genes? A benchmark of gene properties for biological and text models

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

  • 5 authors
·
Dec 5, 2024

Scientific Image Synthesis: Benchmarking, Methodologies, and Downstream Utility

While synthetic data has proven effective for improving scientific reasoning in the text domain, multimodal reasoning remains constrained by the difficulty of synthesizing scientifically rigorous images. Existing Text-to-Image (T2I) models often produce outputs that are visually plausible yet scientifically incorrect, resulting in a persistent visual-logic divergence that limits their value for downstream reasoning. Motivated by recent advances in next-generation T2I models, we conduct a systematic study of scientific image synthesis across generation paradigms, evaluation, and downstream use. We analyze both direct pixel-based generation and programmatic synthesis, and propose ImgCoder, a logic-driven framework that follows an explicit "understand - plan - code" workflow to improve structural precision. To rigorously assess scientific correctness, we introduce SciGenBench, which evaluates generated images based on information utility and logical validity. Our evaluation reveals systematic failure modes in pixel-based models and highlights a fundamental expressiveness-precision trade-off. Finally, we show that fine-tuning Large Multimodal Models (LMMs) on rigorously verified synthetic scientific images yields consistent reasoning gains, with potential scaling trends analogous to the text domain, validating high-fidelity scientific synthesis as a viable path to unlocking massive multimodal reasoning capabilities.

LEOPARD : A Vision Language Model For Text-Rich Multi-Image Tasks

Text-rich images, where text serves as the central visual element guiding the overall understanding, are prevalent in real-world applications, such as presentation slides, scanned documents, and webpage snapshots. Tasks involving multiple text-rich images are especially challenging, as they require not only understanding the content of individual images but reasoning about inter-relationships and logical flows across multiple visual inputs. Despite the importance of these scenarios, current multimodal large language models (MLLMs) struggle to handle such tasks due to two key challenges: (1) the scarcity of high-quality instruction tuning datasets for text-rich multi-image scenarios, and (2) the difficulty in balancing image resolution with visual feature sequence length. To address these challenges, we propose \OurMethod, a MLLM designed specifically for handling vision-language tasks involving multiple text-rich images. First, we curated about one million high-quality multimodal instruction-tuning data, tailored to text-rich, multi-image scenarios. Second, we developed an adaptive high-resolution multi-image encoding module to dynamically optimize the allocation of visual sequence length based on the original aspect ratios and resolutions of the input images. Experiments across a wide range of benchmarks demonstrate our model's superior capabilities in text-rich, multi-image evaluations and competitive performance in general domain evaluations.

Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction

Survival prediction is a complicated ordinal regression task that aims to predict the ranking risk of death, which generally benefits from the integration of histology and genomic data. Despite the progress in joint learning from pathology and genomics, existing methods still suffer from challenging issues: 1) Due to the large size of pathological images, it is difficult to effectively represent the gigapixel whole slide images (WSIs). 2) Interactions within tumor microenvironment (TME) in histology are essential for survival analysis. Although current approaches attempt to model these interactions via co-attention between histology and genomic data, they focus on only dense local similarity across modalities, which fails to capture global consistency between potential structures, i.e. TME-related interactions of histology and co-expression of genomic data. To address these challenges, we propose a Multimodal Optimal Transport-based Co-Attention Transformer framework with global structure consistency, in which optimal transport (OT) is applied to match patches of a WSI and genes embeddings for selecting informative patches to represent the gigapixel WSI. More importantly, OT-based co-attention provides a global awareness to effectively capture structural interactions within TME for survival prediction. To overcome high computational complexity of OT, we propose a robust and efficient implementation over micro-batch of WSI patches by approximating the original OT with unbalanced mini-batch OT. Extensive experiments show the superiority of our method on five benchmark datasets compared to the state-of-the-art methods. The code is released.

  • 2 authors
·
Jun 14, 2023

MMM-RS: A Multi-modal, Multi-GSD, Multi-scene Remote Sensing Dataset and Benchmark for Text-to-Image Generation

Recently, the diffusion-based generative paradigm has achieved impressive general image generation capabilities with text prompts due to its accurate distribution modeling and stable training process. However, generating diverse remote sensing (RS) images that are tremendously different from general images in terms of scale and perspective remains a formidable challenge due to the lack of a comprehensive remote sensing image generation dataset with various modalities, ground sample distances (GSD), and scenes. In this paper, we propose a Multi-modal, Multi-GSD, Multi-scene Remote Sensing (MMM-RS) dataset and benchmark for text-to-image generation in diverse remote sensing scenarios. Specifically, we first collect nine publicly available RS datasets and conduct standardization for all samples. To bridge RS images to textual semantic information, we utilize a large-scale pretrained vision-language model to automatically output text prompts and perform hand-crafted rectification, resulting in information-rich text-image pairs (including multi-modal images). In particular, we design some methods to obtain the images with different GSD and various environments (e.g., low-light, foggy) in a single sample. With extensive manual screening and refining annotations, we ultimately obtain a MMM-RS dataset that comprises approximately 2.1 million text-image pairs. Extensive experimental results verify that our proposed MMM-RS dataset allows off-the-shelf diffusion models to generate diverse RS images across various modalities, scenes, weather conditions, and GSD. The dataset is available at https://github.com/ljl5261/MMM-RS.

  • 10 authors
·
Oct 25, 2024

LLaVA-SP: Enhancing Visual Representation with Visual Spatial Tokens for MLLMs

The architecture of multimodal large language models (MLLMs) commonly connects a vision encoder, often based on CLIP-ViT, to a large language model. While CLIP-ViT works well for capturing global image features, it struggles to model local relationships between adjacent patches, leading to weaker visual representation, which in turn affects the detailed understanding ability of MLLMs. To solve this, we propose LLaVA-SP, which only adds six spatial visual tokens to the original visual tokens to enhance the visual representation. Our approach offers three key advantages: 1)We propose a novel Projector, which uses convolutional kernels to derive visual spatial tokens from ViT patch features, simulating two visual spatial ordering approaches: ``from central region to global" and ``from abstract to specific". Then, a cross-attention mechanism is applied to fuse fine-grained visual information, enriching the overall visual representation. 2) We present two model variants: LLaVA-SP-Cropping, which focuses on detail features through progressive cropping, and LLaVA-SP-Pooling, which captures global semantics through adaptive pooling, enabling the model to handle diverse visual understanding tasks. 3) Extensive experiments show that LLaVA-SP, fine-tuned with LoRA, achieves significant performance improvements across various multimodal benchmarks, outperforming the state-of-the-art LLaVA-1.5 model in multiple tasks with nearly identical inference latency. The code and models are available at https://github.com/CnFaker/LLaVA-SP.

  • 5 authors
·
Jul 1, 2025

Semi-Parametric Neural Image Synthesis

Novel architectures have recently improved generative image synthesis leading to excellent visual quality in various tasks. Much of this success is due to the scalability of these architectures and hence caused by a dramatic increase in model complexity and in the computational resources invested in training these models. Our work questions the underlying paradigm of compressing large training data into ever growing parametric representations. We rather present an orthogonal, semi-parametric approach. We complement comparably small diffusion or autoregressive models with a separate image database and a retrieval strategy. During training we retrieve a set of nearest neighbors from this external database for each training instance and condition the generative model on these informative samples. While the retrieval approach is providing the (local) content, the model is focusing on learning the composition of scenes based on this content. As demonstrated by our experiments, simply swapping the database for one with different contents transfers a trained model post-hoc to a novel domain. The evaluation shows competitive performance on tasks which the generative model has not been trained on, such as class-conditional synthesis, zero-shot stylization or text-to-image synthesis without requiring paired text-image data. With negligible memory and computational overhead for the external database and retrieval we can significantly reduce the parameter count of the generative model and still outperform the state-of-the-art.

  • 5 authors
·
Apr 25, 2022

Memory-Augmented Incomplete Multimodal Survival Prediction via Cross-Slide and Gene-Attentive Hypergraph Learning

Multimodal pathology-genomic analysis is critical for cancer survival prediction. However, existing approaches predominantly integrate formalin-fixed paraffin-embedded (FFPE) slides with genomic data, while neglecting the availability of other preservation slides, such as Fresh Froze (FF) slides. Moreover, as the high-resolution spatial nature of pathology data tends to dominate the cross-modality fusion process, it hinders effective multimodal fusion and leads to modality imbalance challenges between pathology and genomics. These methods also typically require complete data modalities, limiting their clinical applicability with incomplete modalities, such as missing either pathology or genomic data. In this paper, we propose a multimodal survival prediction framework that leverages hypergraph learning to effectively integrate multi-WSI information and cross-modality interactions between pathology slides and genomics data while addressing modality imbalance. In addition, we introduce a memory mechanism that stores previously learned paired pathology-genomic features and dynamically compensates for incomplete modalities. Experiments on five TCGA datasets demonstrate that our model outperforms advanced methods by over 2.3% in C-Index. Under incomplete modality scenarios, our approach surpasses pathology-only (3.3%) and gene-only models (7.9%). Code: https://github.com/MCPathology/M2Surv

  • 7 authors
·
Jun 24, 2025

Holi-Spatial: Evolving Video Streams into Holistic 3D Spatial Intelligence

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.

  • 17 authors
·
Mar 8 5

Zero-shot spatial layout conditioning for text-to-image diffusion models

Large-scale text-to-image diffusion models have significantly improved the state of the art in generative image modelling and allow for an intuitive and powerful user interface to drive the image generation process. Expressing spatial constraints, e.g. to position specific objects in particular locations, is cumbersome using text; and current text-based image generation models are not able to accurately follow such instructions. In this paper we consider image generation from text associated with segments on the image canvas, which combines an intuitive natural language interface with precise spatial control over the generated content. We propose ZestGuide, a zero-shot segmentation guidance approach that can be plugged into pre-trained text-to-image diffusion models, and does not require any additional training. It leverages implicit segmentation maps that can be extracted from cross-attention layers, and uses them to align the generation with input masks. Our experimental results combine high image quality with accurate alignment of generated content with input segmentations, and improve over prior work both quantitatively and qualitatively, including methods that require training on images with corresponding segmentations. Compared to Paint with Words, the previous state-of-the art in image generation with zero-shot segmentation conditioning, we improve by 5 to 10 mIoU points on the COCO dataset with similar FID scores.

  • 5 authors
·
Jun 23, 2023 1

Spatial-MLLM: Boosting MLLM Capabilities in Visual-based Spatial Intelligence

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/.

  • 4 authors
·
May 29, 2025 3

URECA: Unique Region Caption Anything

Region-level captioning aims to generate natural language descriptions for specific image regions while highlighting their distinguishing features. However, existing methods struggle to produce unique captions across multi-granularity, limiting their real-world applicability. To address the need for detailed region-level understanding, we introduce URECA dataset, a large-scale dataset tailored for multi-granularity region captioning. Unlike prior datasets that focus primarily on salient objects, URECA dataset ensures a unique and consistent mapping between regions and captions by incorporating a diverse set of objects, parts, and background elements. Central to this is a stage-wise data curation pipeline, where each stage incrementally refines region selection and caption generation. By leveraging Multimodal Large Language Models (MLLMs) at each stage, our pipeline produces distinctive and contextually grounded captions with improved accuracy and semantic diversity. Building upon this dataset, we present URECA, a novel captioning model designed to effectively encode multi-granularity regions. URECA maintains essential spatial properties such as position and shape through simple yet impactful modifications to existing MLLMs, enabling fine-grained and semantically rich region descriptions. Our approach introduces dynamic mask modeling and a high-resolution mask encoder to enhance caption uniqueness. Experiments show that URECA achieves state-of-the-art performance on URECA dataset and generalizes well to existing region-level captioning benchmarks.

  • 5 authors
·
Apr 7, 2025 4

DendroMap: Visual Exploration of Large-Scale Image Datasets for Machine Learning with Treemaps

In this paper, we present DendroMap, a novel approach to interactively exploring large-scale image datasets for machine learning (ML). ML practitioners often explore image datasets by generating a grid of images or projecting high-dimensional representations of images into 2-D using dimensionality reduction techniques (e.g., t-SNE). However, neither approach effectively scales to large datasets because images are ineffectively organized and interactions are insufficiently supported. To address these challenges, we develop DendroMap by adapting Treemaps, a well-known visualization technique. DendroMap effectively organizes images by extracting hierarchical cluster structures from high-dimensional representations of images. It enables users to make sense of the overall distributions of datasets and interactively zoom into specific areas of interests at multiple levels of abstraction. Our case studies with widely-used image datasets for deep learning demonstrate that users can discover insights about datasets and trained models by examining the diversity of images, identifying underperforming subgroups, and analyzing classification errors. We conducted a user study that evaluates the effectiveness of DendroMap in grouping and searching tasks by comparing it with a gridified version of t-SNE and found that participants preferred DendroMap. DendroMap is available at https://div-lab.github.io/dendromap/.

  • 7 authors
·
May 13, 2022

Dissecting CLIP: Decomposition with a Schur Complement-based Approach

The use of CLIP embeddings to assess the alignment of samples produced by text-to-image generative models has been extensively explored in the literature. While the widely adopted CLIPScore, derived from the cosine similarity of text and image embeddings, effectively measures the relevance of a generated image, it does not quantify the diversity of images generated by a text-to-image model. In this work, we extend the application of CLIP embeddings to quantify and interpret the intrinsic diversity of text-to-image models, which is responsible for generating diverse images from similar text prompts. To achieve this, we propose a decomposition of the CLIP-based kernel covariance matrix of image data into text-based and non-text-based components. Using the Schur complement of the joint image-text kernel covariance matrix, we perform this decomposition and define the matrix-based entropy of the decomposed component as the Schur Complement Entropy (SCE) score, a measure of the intrinsic diversity of a text-to-image model based on data collected with varying text prompts. Additionally, we demonstrate the use of the Schur complement-based decomposition to nullify the influence of a given prompt in the CLIP embedding of an image, enabling focus or defocus of embeddings on specific objects or properties for downstream tasks. We present several numerical results that apply our Schur complement-based approach to evaluate text-to-image models and modify CLIP image embeddings. The codebase is available at https://github.com/aziksh-ospanov/CLIP-DISSECTION

  • 3 authors
·
Dec 24, 2024

Enhancing Few-Shot Image Classification through Learnable Multi-Scale Embedding and Attention Mechanisms

In the context of few-shot classification, the goal is to train a classifier using a limited number of samples while maintaining satisfactory performance. However, traditional metric-based methods exhibit certain limitations in achieving this objective. These methods typically rely on a single distance value between the query feature and support feature, thereby overlooking the contribution of shallow features. To overcome this challenge, we propose a novel approach in this paper. Our approach involves utilizing a multi-output embedding network that maps samples into distinct feature spaces. The proposed method extracts feature vectors at different stages, enabling the model to capture both global and abstract features. By utilizing these diverse feature spaces, our model enhances its performance. Moreover, employing a self-attention mechanism improves the refinement of features at each stage, leading to even more robust representations and improved overall performance. Furthermore, assigning learnable weights to each stage significantly improved performance and results. We conducted comprehensive evaluations on the MiniImageNet and FC100 datasets, specifically in the 5-way 1-shot and 5-way 5-shot scenarios. Additionally, we performed cross-domain tasks across eight benchmark datasets, achieving high accuracy in the testing domains. These evaluations demonstrate the efficacy of our proposed method in comparison to state-of-the-art approaches. https://github.com/FatemehAskari/MSENet

  • 3 authors
·
Sep 12, 2024

Why Far Looks Up: Probing Spatial Representation in Vision-Language Models

Vision-language models (VLMs) achieve strong performance on spatial reasoning benchmarks, yet it remains unclear whether this reflects structured 3D understanding or reliance on statistical shortcuts in natural images. We introduce a representation-level analysis framework that constructs minimal contrastive pairs to measure how spatial axes are organized and disentangled within VLM embeddings. Our analysis across multiple model families reveals a consistent vertical-distance entanglement: models conflate vertical image position with distance, mirroring the perspective bias of natural photographs. This bias produces a significant accuracy gap between perspective-consistent and counter-heuristic examples, and intensifies under data scaling even as overall benchmark accuracy improves. We further show that models with similar benchmark scores can exhibit different internal representations, and that these differences predict accuracy and robustness across diverse spatial reasoning benchmarks. To isolate this bias from evaluation-set skew, we introduce SpatialTunnel, a synthetic benchmark designed to expose spatial shortcut biases by removing common correlations present in natural images. Experiments confirm that the entanglement is model-intrinsic, and that models with well-separated spatial axes exhibit greater robustness, suggesting that well-structured spatial representations lead to more reliable spatial reasoning across diverse benchmarks. Code and benchmark are available on the project page: https://cheolhong0916.github.io/whyfarlooksup.github.io/.

nvidia NVIDIA
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May 27 3