Abstract:Motivation: Low-dimensional embeddings are widely used to explore cell-state heterogeneity in single-cell and other high-dimensional biological data. Although many methods preserve local neighborhoods, they may distort the apparent sampling density of processed observations, altering the visual contrast between dense and sparse regions and complicating the interpretation of rare, transitional, or continuous cell-state populations. Results: We present DMT-Dens, a parametric manifold-visualization method built on a latent-token Transformer encoder. The model integrates rank-based manifold alignment with hard-pair aggregation. To preserve density, it optimizes a loss based on the Pearson correlation between k-nearest-neighbor log-radius estimates in the processed input and two-dimensional embedding spaces. Benchmark evaluations demonstrate strong density preservation, particularly on biological datasets, while retaining competitive label separability. Availability: Source code, data-processing scripts, and resolved experiment configurations are available at https://github.com/Ruizhe-wang/DMT-Dens.
Abstract:Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes. Here we present BioM-JEPA, a joint-embedding predictive architecture that instead predicts aggregate representations of graph-connected gene blocks defined by protein-association and corpus-derived coexpression evidence. A student network infers each target-block representation from the remaining genes in a cell, while a slowly updated teacher supplies the corresponding target from the full observed gene set. Under the reported extraction procedure, block-level prediction produced embeddings with higher effective rank and weaker association with detected-gene depth in the tested diagnostics than token-prediction, random-block and reconstruction controls. Across CellBench tasks, frozen BioM-JEPA embeddings retained expression, pathway and neighbourhood information and achieved the lowest aggregate perturbation-response error among the evaluated models. Representation diagnostics were also consistent with canonical pancreatic programmes and compositional relationships between genetic perturbations. Linear attention avoids constructing a quadratic gene-by-gene attention matrix; in a matched one-epoch hPancreas experiment at batch size 8, BioM-JEPA provided 5.75-fold higher fine-tuning throughput and 3.76-fold higher held-out embedding throughput than scFoundation. Together, these results support graph-connected gene blocks as useful prediction units for JEPA-style representation learning in single-cell biology.
Abstract:A critical challenge in single-cell RNA sequencing (scRNA-seq) integration is resolving the tension between eliminating batch effects and maintaining biological fidelity. While recent evidence indicates that batch effects manifest heterogeneously across genes, most existing methods process the transcriptome uniformly, frequently resulting in over-correction and loss of subtle biological signals. To address this, we present scHelix, a dataset-adaptive framework that fundamentally changes how features are processed by explicitly partitioning genes into domain-invariant Anchors and domain-sensitive Variants at the input level. scHelix utilizes a dual-stream sparse diffusion encoder equipped with stop-gradient graph caching to efficiently learn multi-scale structural representations. The core of our approach is a novel asymmetric Align-Refine-Fuse protocol: the unstable Variant stream is first aligned to the robust topology of the Anchor stream, followed by a conservative refinement phase where the Anchor stream absorbs denoised details via bounded residual gating. This divide-and-conquer architecture prevents shortcut learning and ensures robust batch removal without compromising the integrity of biological clusters. Extensive benchmarking demonstrates that scHelix outperforms state-of-the-art methods.
Abstract:Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.
Abstract:Automated cellular reasoning faces a core dichotomy: supervised methods fall into the Reference Trap and fail to generalize to out-of-distribution cell states, while large language models (LLMs), without grounded biological priors, suffer from a Signal-to-Noise Paradox that produces spurious associations. We propose MAT-Cell, a neuro-symbolic reasoning framework that reframes single-cell analysis from black-box classification into constructive, verifiable proof generation. MAT-Cell injects symbolic constraints through adaptive Retrieval-Augmented Generation (RAG) to ground neural reasoning in biological axioms and reduce transcriptomic noise. It further employs a dialectic verification process with homogeneous rebuttal agents to audit and prune reasoning paths, forming syllogistic derivation trees that enforce logical consistency.Across large-scale and cross-species benchmarks, MAT-Cell significantly outperforms state-of-the-art (SOTA) models and maintains robust per-formance in challenging scenarios where baselinemethods severely degrade. Code is available at https://gith ub.com/jiangliu91/MAT-Cell-A-Mul ti-Agent-Tree-Structured-Reasoni ng-Framework-for-Batch-Level-Sin gle-Cell-Annotation.
Abstract:Unsupervised Domain Adaptation (UDA) seeks to transfer knowledge from a labeled source domain to an unlabeled target domain but often suffers from severe domain and scale gaps that degrade performance. Existing cross-attention-based transformers can align features across domains, yet they struggle to preserve content semantics under large appearance and scale variations. To explicitly address these challenges, we introduce the concept of beneficial noise, which regularizes cross-attention by injecting controlled perturbations, encouraging the model to ignore style distractions and focus on content. We propose the Domain-Adaptive Cross-Scale Matching (DACSM) framework, which consists of a Domain-Adaptive Transformer (DAT) for disentangling domain-shared content from domain-specific style, and a Cross-Scale Matching (CSM) module that adaptively aligns features across multiple resolutions. DAT incorporates beneficial noise into cross-attention, enabling progressive domain translation with enhanced robustness, yielding content-consistent and style-invariant representations. Meanwhile, CSM ensures semantic consistency under scale changes. Extensive experiments on VisDA-2017, Office-Home, and DomainNet demonstrate that DACSM achieves state-of-the-art performance, with up to +2.3% improvement over CDTrans on VisDA-2017. Notably, DACSM achieves a +5.9% gain on the challenging "truck" class of VisDA, evidencing the strength of beneficial noise in handling scale discrepancies. These results highlight the effectiveness of combining domain translation, beneficial-noise-enhanced attention, and scale-aware alignment for robust cross-domain representation learning.
Abstract:We propose LaPha, a method for training AlphaZero-like LLM agents in a Poincaré latent space. Under LaPha, the search process can be visualized as a tree rooted at the prompt and growing outward from the origin toward the boundary of the Poincaré ball, where negative curvature provides exponentially increasing capacity with radius. Using hyperbolic geodesic distance to rule-verified correctness, we define a node potential and assign dense process rewards by potential differences. We further attach a lightweight value head on the same shared latent space, enabling self-guided test-time scaling with almost no additional overhead. On MATH-500, LaPha improves Qwen2.5-Math-1.5B from 66.0% to 88.2%. With value-head-guided search, LaPha-1.5B reaches 56.7% accuracy on AIME'24, and LaPha-7B further achieves 60.0% on AIME'24 and 53.3% on AIME'25.
Abstract:While foundation models have advanced surgical video analysis, current approaches rely predominantly on pixel-level reconstruction objectives that waste model capacity on low-level visual details - such as smoke, specular reflections, and fluid motion - rather than semantic structures essential for surgical understanding. We present UniSurg, a video-native foundation model that shifts the learning paradigm from pixel-level reconstruction to latent motion prediction. Built on the Video Joint Embedding Predictive Architecture (V-JEPA), UniSurg introduces three key technical innovations tailored to surgical videos: 1) motion-guided latent prediction to prioritize semantically meaningful regions, 2) spatiotemporal affinity self-distillation to enforce relational consistency, and 3) feature diversity regularization to prevent representation collapse in texture-sparse surgical scenes. To enable large-scale pretraining, we curate UniSurg-15M, the largest surgical video dataset to date, comprising 3,658 hours of video from 50 sources across 13 anatomical regions. Extensive experiments across 17 benchmarks demonstrate that UniSurg significantly outperforms state-of-the-art methods on surgical workflow recognition (+14.6% F1 on EgoSurgery, +10.3% on PitVis), action triplet recognition (39.54% mAP-IVT on CholecT50), skill assessment, polyp segmentation, and depth estimation. These results establish UniSurg as a new standard for universal, motion-oriented surgical video understanding.
Abstract:With the rapid growth of large language models (LLMs) and vision-language models (VLMs) in medicine, simply integrating clinical text and medical imaging does not guarantee reliable reasoning. Existing multimodal models often produce hallucinations or inconsistent chains of thought, limiting clinical trust. We propose a diagnostic framework built upon LLaVA that combines vision-language alignment with logic-regularized reasoning. The system includes an input encoder for text and images, a projection module for cross-modal alignment, a reasoning controller that decomposes diagnostic tasks into steps, and a logic tree generator that assembles stepwise premises into verifiable conclusions. Evaluations on MedXpertQA and other benchmarks show that our method improves diagnostic accuracy and yields more interpretable reasoning traces on multimodal tasks, while remaining competitive on text-only settings. These results suggest a promising step toward trustworthy multimodal medical AI.
Abstract:Multimodal Large Language Models (MLLMs) have achieved impressive progress in natural image reasoning, yet their potential in medical imaging remains underexplored, especially in clinical anatomical surgical images. Anatomy understanding tasks demand precise understanding and clinically coherent answers, which are difficult to achieve due to the complexity of medical data and the scarcity of high-quality expert annotations. These challenges limit the effectiveness of conventional Supervised Fine-Tuning (SFT) strategies. While recent work has demonstrated that Group Relative Policy Optimization (GRPO) can enhance reasoning in MLLMs without relying on large amounts of data, we find two weaknesses that hinder GRPO's reasoning performance in anatomy recognition: 1) knowledge cannot be effectively shared between different anatomical structures, resulting in uneven information gain and preventing the model from converging, and 2) the model quickly converges to a single reasoning path, suppressing the exploration of diverse strategies. To overcome these challenges, we propose two novel methods. First, we implement a progressive learning strategy called Anatomical Similarity Curriculum Learning by controlling question difficulty via the similarity of answer choices, enabling the model to master complex problems incrementally. Second, we utilize question augmentation referred to as Group Diversity Question Augmentation to expand the model's search space for difficult queries, mitigating the tendency to produce uniform responses. Comprehensive experiments on the SGG-VQA and OmniMedVQA benchmarks show our method achieves a significant improvement across the two benchmarks, demonstrating its effectiveness in enhancing the medical reasoning capabilities of MLLMs. The code can be found in https://github.com/tomato996/Anatomy-R1