arXiv subjects

Zhi Huang

Publications and source records attributed to Zhi Huang.

At least 19 recordsLinked to original sources

arXiv2026

CytoFormer: A Molecularly Supervised Cell Foundation Model for Histopathology Cell Classification

Identifying cell types directly from routine haematoxylin and eosin (H&E) histology would enable single-cell analysis at scale, but training such models has relied on manual pathologist annotations, which are slow, expensive and unreliable for many cell types. We instead supervise morphology with molecules. Imaging-based spatial transcriptomics profiles individual cells in situ on a section that can afterwards be stained with H&E, so that molecular identity and morphology are observed for the same physical cell. We assembled 81 such paired Xenium sections spanning 16 organs, derived per-cell labels by clustering, marker-gene annotation, organ-wise human review and quality control, and mapped them onto the cell types commonly reported in each organ. This yielded 15.4 million cells, each with a paired H&E image patch and one of 23 cell types, on which we trained CytoFormer, a cell foundation model with a multi-task, per-organ classification head. On spatially held-out tissue CytoFormer reached an accuracy of 0.85 and a macro-F1 of 0.78 across all 16 organs, and its predictions reproduced the tissue architecture of an entire held-out section. The representation also transfers: with the encoder frozen, a linear head on CytoFormer features performed better than six pathology foundation models on four expert-annotated benchmarks, including on organs and cell types that were not part of pretraining. Finally, in an interactive active-learning setting, CytoFormer's embeddings are markedly more label-efficient than existing pathology foundation models, detecting normal epithelium amid look-alike tumour with an F1 of 0.82 from only a few annotations and leading the strongest baseline by 0.13 in F1. CytoFormer turns paired H&E and spatial transcriptomics into a reusable, label-efficient representation for cell-level analysis of routine histology.

cs.CV↗

arXiv2026

ProBAG: Prototype-Guided Boundary-Aware Graph Diffusion for Weakly Supervised Histopathology Segmentation

Weakly supervised semantic segmentation enables histopathology tissue segmentation from image-level annotations, avoiding costly pixel-level labeling by expert pathologists. However, CAM-based methods often localize only highly discriminative regions and remain unreliable near tissue interfaces. We propose ProBAG, a stage-1 pseudo-mask generator that combines dataset-specific visual prototypes with pathology-aligned CONCH text prototypes over multi-scale frozen UNI features. ProBAG introduces two complementary mechanisms: class-wise power recalibration that reshapes inter-class competition while preserving the total foreground activation mass at each pixel, and one-step graph diffusion in which feature affinities are penalized by a late-transformer attention-context discrepancy used as a soft structural boundary cue. The resulting stage-1 pseudo-masks require neither CRF nor an external segmentation model; for complete two-stage comparison, they additionally supervise a downstream Phikon-FPN segmenter. Experiments on BCSS-WSSS and LUAD-HistoSeg show consistent gains over recent WSSS approaches, while ablations indicate that pathology-aligned text semantics provide the largest improvement and graph refinement provides a smaller complementary gain. The code is available at: https://github.com/wterrr/WSSS

cs.CV↗

arXiv2026

CoDiR: Confidence-Guided Diffusion Refinement for Semi-Supervised Histopathology Segmentation

Semi-supervised histopathology segmentation is challenging due to scarce annotations and unreliable pseudo-labels in ambiguous gland regions. To address this problem, we propose Confidence-Guided Diffusion Refinement (CoDiR), a semi-supervised framework that combines a Mean Teacher segmentation model with diffusion-based pseudo-label refinement. Given an unlabeled image, the teacher first produces a soft prediction, and only low-confidence regions are refined by a conditional diffusion model trained to capture plausible mask structures from labeled data. The refined mask is then fused with reliable teacher predictions and used to train the student with confidence weighting and consistency regularization. On the GlaS and CRAG datasets CoDiR reaches 88.09\% and 89.83\% mDice with 10\% labeled data, and 89.19\% and 90.29\% mDice with 20\%, matching or exceeding the strongest published method on seven of the eight benchmark metrics. Ablations attribute the largest single contribution to the refinement module, which adds +6.36\% mDice over the Mean Teacher baseline. The implementation code is publicly available at: https://github.com/vongla345/codir

cs.CV↗

arXiv2026

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.

cs.LG↗

arXiv2026

iSight: Towards expert-AI co-assessment for improved immunohistochemistry staining interpretation

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's $\kappa$ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

cs.CV↗

arXiv2026

VISTA-PATH: An interactive foundation model for pathology image segmentation and quantitative analysis in computational pathology

Accurate semantic segmentation for histopathology image is crucial for quantitative tissue analysis and downstream clinical modeling. Recent segmentation foundation models have improved generalization through large-scale pretraining, yet remain poorly aligned with pathology because they treat segmentation as a static visual prediction task. Here we present VISTA-PATH, an interactive, class-aware pathology segmentation foundation model designed to resolve heterogeneous structures, incorporate expert feedback, and produce pixel-level segmentation that are directly meaningful for clinical interpretation. VISTA-PATH jointly conditions segmentation on visual context, semantic tissue descriptions, and optional expert-provided spatial prompts, enabling precise multi-class segmentation across heterogeneous pathology images. To support this paradigm, we curate VISTA-PATH Data, a large-scale pathology segmentation corpus comprising over 1.6 million image-mask-text triplets spanning 9 organs and 93 tissue classes. Across extensive held-out and external benchmarks, VISTA-PATH consistently outperforms existing segmentation foundation models. Importantly, VISTA-PATH supports dynamic human-in-the-loop refinement by propagating sparse, patch-level bounding-box annotation feedback into whole-slide segmentation. Finally, we show that the high-fidelity, class-aware segmentation produced by VISTA-PATH is a preferred model for computational pathology. It improve tissue microenvironment analysis through proposed Tumor Interaction Score (TIS), which exhibits strong and significant associations with patient survival. Together, these results establish VISTA-PATH as a foundation model that elevates pathology image segmentation from a static prediction to an interactive and clinically grounded representation for digital pathology. Source code and demo can be found at https://github.com/zhihuanglab/VISTA-PATH.

cs.CV↗

arXiv2025

Adaptive Multi-Scale Integration Unlocks Robust Cell Annotation in Histopathology Images

Identifying cell types and subtypes in routine histopathology is fundamental for understanding disease. Existing tile-based models capture nuclear detail but miss the broader tissue context that influences cell identity. Current human annotations are coarse-grained and uneven across studies, making fine-grained, subtype-level classification difficult. In this study, we build a marker-guided dataset from Xenium spatial transcriptomics with single-cell resolution labels for more than two million cells across eight organs and 16 classes to address the lack of high-quality annotations. Leveraging this data resource, we introduce NuClass, a pathologist workflow inspired framework for cell-wise multi-scale integration of nuclear morphology and microenvironmental context. It combines Path local, which focuses on nuclear morphology from 224x224 pixel crops, and Path global, which models the surrounding 1024x1024 pixel neighborhood, through a learnable gating module that balances local and global information. An uncertainty-guided objective directs the global path to prioritize regions where the local path is uncertain, and we provide calibrated confidence estimates and Grad-CAM maps for interpretability. Evaluated on three fully held-out cohorts, NuClass achieves up to 96 percent F1 for its best-performing class, outperforming strong baselines. Our results demonstrate that multi-scale, uncertainty-aware fusion can bridge the gap between slide-level pathological foundation models and reliable, cell-level phenotype prediction.

cs.CV↗

arXiv2025

Pathology-CoT: Learning Visual Chain-of-Thought Agent from Expert Whole Slide Image Diagnosis Behavior

Diagnosing a whole-slide image is an interactive, multi-stage process of changing magnification and moving between fields. Although recent pathology foundation models demonstrated superior performances, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. Such limitation is largely bottlenecked by data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not documented in textbooks or internet, and therefore absent from LLM training. Here we introduce a framework designed to address this challenge through three key breakthroughs. First, the AI Session Recorder seamlessly integrates with standard whole-slide image viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands and bounding boxes. Second, a lightweight human-in-the-loop review turns AI-drafted rationales for behavioral commands into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters", enabling six-fold faster labeling compared to manual constructing such Chain-of-Thought dataset. Using this behavioral data, we build Pathology-o3, a two-stage agent that first proposes important ROIs and then performs behavior-guided reasoning. On the gastrointestinal lymph-node metastasis detection task, our method achieved 100 recall on the internal validation from Stanford Medicine and 97.6 recall on an independent external validation from Sweden, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, Pathology-CoT constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

cs.CV↗

arXiv2025

A co-evolving agentic AI system for medical imaging analysis

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

cs.CV↗

arXiv2025

CellForge: Agentic Design of Virtual Cell Models

Virtual cell modeling aims to predict cellular responses to diverse perturbations but faces challenges from biological complexity, multimodal data heterogeneity, and the need for interdisciplinary expertise. We introduce CellForge, a multi-agent framework that autonomously designs and synthesizes neural network architectures tailored to specific single-cell datasets and perturbation tasks. Given raw multi-omics data and task descriptions, CellForge discovers candidate architectures through collaborative reasoning among specialized agents, then generates executable implementations. Our core contribution is the framework itself: showing that multi-agent collaboration mechanisms - rather than manual human design or single-LLM prompting - can autonomously produce executable, high-quality computational methods. This approach goes beyond conventional hyperparameter tuning by enabling entirely new architectural components such as trajectory-aware encoders and perturbation diffusion modules to emerge from agentic deliberation. We evaluate CellForge on six datasets spanning gene knockouts, drug treatments, and cytokine stimulations across multiple modalities (scRNA-seq, scATAC-seq, CITE-seq). The results demonstrate that the models generated by CellForge are highly competitive with established baselines, while revealing systematic patterns of architectural innovation. CellForge highlights the scientific value of multi-agent frameworks: collaboration among specialized agents enables genuine methodological innovation and executable solutions that single agents or human experts cannot achieve. This represents a paradigm shift toward autonomous scientific method development in computational biology. Code is available at https://github.com/gersteinlab/CellForge.

cs.LG↗

arXiv2025

Can Textual Gradient Work in Federated Learning?

Recent studies highlight the promise of LLM-based prompt optimization, especially with TextGrad, which automates differentiation'' via texts and backpropagates textual feedback. This approach facilitates training in various real-world applications that do not support numerical gradient propagation or loss calculation. In this paper, we systematically explore the potential and challenges of incorporating textual gradient into Federated Learning (FL). Our contributions are fourfold. Firstly, we introduce a novel FL paradigm, Federated Textual Gradient (FedTextGrad), that allows clients to upload locally optimized prompts derived from textual gradients, while the server aggregates the received prompts. Unlike traditional FL frameworks, which are designed for numerical aggregation, FedTextGrad is specifically tailored for handling textual data, expanding the applicability of FL to a broader range of problems that lack well-defined numerical loss functions. Secondly, building on this design, we conduct extensive experiments to explore the feasibility of FedTextGrad. Our findings highlight the importance of properly tuning key factors (e.g., local steps) in FL training. Thirdly, we highlight a major challenge in FedTextGrad aggregation: retaining essential information from distributed prompt updates. Last but not least, in response to this issue, we improve the vanilla variant of FedTextGrad by providing actionable guidance to the LLM when summarizing client prompts by leveraging the Uniform Information Density principle. Through this principled study, we enable the adoption of textual gradients in FL for optimizing LLMs, identify important issues, and pinpoint future directions, thereby opening up a new research area that warrants further investigation.

cs.LG↗

arXiv2024

TextGrad: Automatic "Differentiation" via Text

AI is undergoing a paradigm shift, with breakthroughs achieved by systems orchestrating multiple large language models (LLMs) and other complex components. As a result, developing principled and automated optimization methods for compound AI systems is one of the most important new challenges. Neural networks faced a similar challenge in its early days until backpropagation and automatic differentiation transformed the field by making optimization turn-key. Inspired by this, we introduce TextGrad, a powerful framework performing automatic ``differentiation'' via text. TextGrad backpropagates textual feedback provided by LLMs to improve individual components of a compound AI system. In our framework, LLMs provide rich, general, natural language suggestions to optimize variables in computation graphs, ranging from code snippets to molecular structures. TextGrad follows PyTorch's syntax and abstraction and is flexible and easy-to-use. It works out-of-the-box for a variety of tasks, where the users only provide the objective function without tuning components or prompts of the framework. We showcase TextGrad's effectiveness and generality across a diverse range of applications, from question answering and molecule optimization to radiotherapy treatment planning. Without modifying the framework, TextGrad improves the zero-shot accuracy of GPT-4o in Google-Proof Question Answering from $51\%$ to $55\%$, yields $20\%$ relative performance gain in optimizing LeetCode-Hard coding problem solutions, improves prompts for reasoning, designs new druglike small molecules with desirable in silico binding, and designs radiation oncology treatment plans with high specificity. TextGrad lays a foundation to accelerate the development of the next-generation of AI systems.

cs.CL↗

arXiv2024

Mapping the Increasing Use of LLMs in Scientific Papers

Scientific publishing lays the foundation of science by disseminating research findings, fostering collaboration, encouraging reproducibility, and ensuring that scientific knowledge is accessible, verifiable, and built upon over time. Recently, there has been immense speculation about how many people are using large language models (LLMs) like ChatGPT in their academic writing, and to what extent this tool might have an effect on global scientific practices. However, we lack a precise measure of the proportion of academic writing substantially modified or produced by LLMs. To address this gap, we conduct the first systematic, large-scale analysis across 950,965 papers published between January 2020 and February 2024 on the arXiv, bioRxiv, and Nature portfolio journals, using a population-level statistical framework to measure the prevalence of LLM-modified content over time. Our statistical estimation operates on the corpus level and is more robust than inference on individual instances. Our findings reveal a steady increase in LLM usage, with the largest and fastest growth observed in Computer Science papers (up to 17.5%). In comparison, Mathematics papers and the Nature portfolio showed the least LLM modification (up to 6.3%). Moreover, at an aggregate level, our analysis reveals that higher levels of LLM-modification are associated with papers whose first authors post preprints more frequently, papers in more crowded research areas, and papers of shorter lengths. Our findings suggests that LLMs are being broadly used in scientific writings.

cs.CL↗

arXiv2024

Monitoring AI-Modified Content at Scale: A Case Study on the Impact of ChatGPT on AI Conference Peer Reviews

We present an approach for estimating the fraction of text in a large corpus which is likely to be substantially modified or produced by a large language model (LLM). Our maximum likelihood model leverages expert-written and AI-generated reference texts to accurately and efficiently examine real-world LLM-use at the corpus level. We apply this approach to a case study of scientific peer review in AI conferences that took place after the release of ChatGPT: ICLR 2024, NeurIPS 2023, CoRL 2023 and EMNLP 2023. Our results suggest that between 6.5% and 16.9% of text submitted as peer reviews to these conferences could have been substantially modified by LLMs, i.e. beyond spell-checking or minor writing updates. The circumstances in which generated text occurs offer insight into user behavior: the estimated fraction of LLM-generated text is higher in reviews which report lower confidence, were submitted close to the deadline, and from reviewers who are less likely to respond to author rebuttals. We also observe corpus-level trends in generated text which may be too subtle to detect at the individual level, and discuss the implications of such trends on peer review. We call for future interdisciplinary work to examine how LLM use is changing our information and knowledge practices.

cs.CL↗

arXiv2023

Hydrogel modified evaporation interface for highly stable membrane distillation

Surface effect of low-surface-tension contaminants accumulating at the evaporation surface can easily induce membrane wetting in the application of membrane distillation, especially in hypersaline scenarios. In this work, we propose a novel strategy to eliminate the surface effect and redistribute contaminants at the evaporation interface with simply incorporating a layer of hydrogel. The as-fabricated composite membrane exhibits remarkable stability, even when exposed to extreme conditions, such as a salt concentration of 5M and surfactant concentration of 8 mM. The breakthrough pressure of the membrane is as high as 20 bars in the presence of surfactants, surpassing commercial hydrophobic membranes by one to two magnitudes. Combined study of density functional theory and molecular dynamics simulations reveals the important role of hydrogel-surfactant interaction in suppressing the surface effect. As a proof of concept, we also demonstrate the stable performance of the membrane in processing synthetic wastewater containing surfactants of 144 mg L-1, mineral oils of 1g L-1 and NaCl of 192 g L-1, showing potential of the membrane in addressing challenges of hypersaline water treatment and zero liquid discharge processes.

physics.chem-ph↗

arXiv2023

A Delay Compensation Framework Based on Eye-Movement for Teleoperated Ground Vehicles

An eye-movement-based predicted trajectory guidance control (ePTGC) is proposed to mitigate the maneuverability degradation of a teleoperated ground vehicle caused by communication delays. Human sensitivity to delays is the main reason for the performance degradation of a ground vehicle teleoperation system. The proposed framework extracts human intention from eye-movement. Then, it combines it with contextual constraints to generate an intention-compliant guidance trajectory, which is then employed to control the vehicle directly. The advantage of this approach is that the teleoperator is removed from the direct control loop by using the generated trajectories to guide vehicle, thus reducing the adverse sensitivity to delay. The delay can be compensated as long as the prediction horizon exceeds the delay. A human-in-loop simulation platform is designed to evaluate the teleoperation performance of the proposed method at different delay levels. The results are analyzed by repeated measures ANOVA, which shows that the proposed method significantly improves maneuverability and cognitive burden at large delay levels (>200 ms). The overall performance is also much better than the PTGC which does not employ the eye-movement feature.

cs.RO↗

arXiv2022

Visual Area of Interests based Multimodal Trajectory Prediction for Probabilistic Risk Assessment

Accurate and reliable prediction of driving intentions and future trajectories contributes to cooperation between human drivers and ADAS in complex traffic environments. This paper proposes a visual AOI (Area of Interest) based multimodal trajectory prediction model for probabilistic risk assessment at intersections. In this study, we find that the visual AOI implies the driving intention and is about 0.6-2.1 s ahead of the operation. Therefore, we designed a trajectory prediction model that integrates the driving intention (DI) and the multimodal trajectory (MT) predictions. The DI model was pre-trained independently to extract the driving intention using features including the visual AOI, historical vehicle states, and environmental context. The intention prediction experiments verify that the visual AOI-based DI model predicts steering intention 0.925 s ahead of the actual steering operation. The trained DI model is then integrated into the trajectory prediction model to filter multimodal trajectories. The trajectory prediction experiments show that the proposed model outperforms the state-of-the-art models. Risk assessment for traffics at intersections verifies that the proposed method achieves high accuracy and a low false alarm rate, and identifies the potential risk about 3 s before a conflict occurs.

cs.HC↗

arXiv2022

Predicted Trajectory Guidance Control Framework of Teleoperated Ground Vehicles Compensating for Delays

Maneuverability and drivability of the teleoperated ground vehicle could be seriously degraded by large communication delays if the delays are not properly compensated. This paper proposes a predicted trajectory guidance control (PTGC) framework to compensate for such delays, thereby improving the performance of the teleoperation system. The novelty of this PTGC framework is that teleoperators intended trajectory is predicted at the vehicle side with their delayed historical control commands and the LiDAR 3D point cloud of the environment, and then the vehicle is guided by the predicted trajectory. By removing the teleoperator from the direct control loop, the presented method is less sensitive to delays, and delays are compensated as long as the prediction horizon exceeds the delays. Human-in-the-loop simulation experiments are designed to evaluate the teleoperation performance with the proposed method under five delay levels. Based on the repeated measurement analysis of variance, it is concluded that the PTGC method can significantly improve the performance of the teleoperated ground vehicles under large delays(>200ms), such as the task completion time (TCT), deviation to centerline (D2C) and steering effort (SE). In addition, the results also show that teleoperators can adapt to smaller delays, and the presented method is ineffective in such cases.

eess.SY↗