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Applications · Health / Medicine

Dexiong Chen, Andrei Manolache, Mathias Niepert, Karsten Borgwardt

Classifying protein topology is essential for deciphering biological function, but progress is held back by the lack of large-scale benchmarks that avoid duplicates and by models that do not scale well. We introduce TEDBench, a large-scale, non-redundant benchmark for protein fold classification constructed from the Encyclopedia of Domains (TED) and Foldseek-clustered AlphaFold structures. We show that on TEDBench, current protein representation learning methods either require very large models or fail to deliver strong performance. To address this challenge, we propose Masked Invariant Autoencoders (MiAE), a self-supervised framework for protein structure representation learning. MiAE uses an extremely high masking ratio of up to 90% with an $\mathrm{SE(3)}$-invariant encoder and a lightweight decoder that reconstructs backbone coordinates from the latent representation and mask tokens. MiAE scales well and outperforms supervised counterparts and state-of-the-art baselines on TEDBench, establishing a strong recipe for protein fold classification. To test transfer beyond AlphaFold structures, we further benchmark on a curated dataset from experimental structures of CATH 4.4. We will release TEDBench and model checkpoints.

Applications · Health / Medicine

Ziyang Liu, Ruiqiang Xiao, Chang Huang, KIEREN YU, Siyuan He, Kaishun WU

Continuous ECG monitoring is clinically valuable, but scaling it beyond electrodes to comfortable long-term use motivates contactless mmWave sensing. In practice, mmWave-to-ECG reconstruction is severely constrained by the scarcity of high-quality synchronized recordings and poor cross-subject generalization. To overcome these bottlenecks, we propose \textbf{Cardio-mmFlow}, a Gaussian-prior-free physics-informed flow matching framework that synthesizes realistic mmWave radar signals from abundant clinical ECG corpora. It learns a direct transport trajectory between the latent manifolds of ECG and radar. To capture subject-dependent propagation differences, we incorporate a simplified mass--spring--damper inspired physical prior and inject it into the flow dynamics via feature-wise linear modulation for personalization. Extensive experiments show that our system have generate high fidelity radar data in both signal and latent domains. It significantly improve zero-shot downstream mmWave$\rightarrow$ECG task, and enable Atrial Fibrillation classification with synthetic data. Further analysis evaluate the model interpretability.

Applications · Health / Medicine

Qi Si, Penglei Wang, Yushuai Wu, Yifeng Jiao, Xuyang Liu, Xin Guo, Yuan Qi, Yuan Cheng

Predicting spatial gene expression from routine H\&E makes high-resolution molecular profiling accessible at scale, especially for large retrospective cohorts. However, current models mostly treat gene expression as a series of pointwise tasks. While effective for numerical fitting, this approach overlooks biological structures: the functional coordination between genes and their organized distribution across tissue. We reframe this task as structured distribution modeling and introduce \textbf{FLAG}, a diffusion-based framework designed to preserve these biological relationships. To capture such structures, a natural strategy would be to jointly model gene expression and their spatial interactions. However, we identify a critical \textbf{Gene Dimension Curse}: such joint modeling fails in high-dimensional gene spaces. This motivates FLAG, which conditions the generative process using a novel spatial graph encoder to ensure gene-spatial topographic coherence and a Gene Foundation Model (GFM) alignment to maintain high gene-gene structural fidelity. To rigorously assess our approach, we propose a structural evaluation metrics, including Gene Structural Correlation (\textbf{GSC}) and Spatial Structural Correlation (\textbf{SSC}). Our experiments demonstrate that FLAG is highly competitive with or superior to state-of-the-art models in traditional accuracy (PCC/MSE), while achieving significantly enhanced structural fidelity in capturing both gene-gene and gene-spatial relationships.

Applications · Health / Medicine

Zhitao He, Haolin Yang, Zeyu Qin, Yi Fung

While Large Language Models (LLMs) have achieved remarkable success in dyadic (one-on-one) instruction, they face significant challenges in One-to-Many alignment, such as clinical ward rounds, where an instructor must simultaneously guide a diverse group of trainees. Current models often suffer from context dilution and goal misalignment, failing to balance individual scaffolding with collective learning progress. To address this, we introduce ClinEdu, a multi-agent pedagogical simulator that model the complexity of group dynamics. Leveraging this platform, we construct ClinTeach, a large-scale dataset of Socratic teaching dialogues, and propose ClinTutor-R1, the first multimodal agent explicitly architected to achieve one-to-many alignment in clinical education, employing an explicit internal thinking mechanism to model both individual belief states and group consensus. We validate our framework through a comprehensive protocol covering both standard static benchmarks and rigorous in-situ interactive evaluation within ClinEdu. Experimental results demonstrate that ClinTutor-R1 outperforms base models by over 20% and achieves parity with proprietary reasoning models , while exhibiting exceptional scalability in maintaining instructional quality across expanding student cohorts.

Applications · Health / Medicine

Yingyu Chen, Yongqiang Huang, Yang Qin, Ziyuan Yang, Lang Yuan, Maosong Ran, Yi Zhang

In clinical practice, patients often present with multiple co-occurring diseases, yet most existing Multi-Label-Diagnosis (MLD) methods treat diagnosis as a rigid discriminative partitioning task, implicitly assuming that overlapping pathologies are separable. This assumption is problematic in medical images, where identical or highly similar visual observations may simultaneously support multiple disease labels, and disease concepts are inherently correlated rather than independent. Enforcing hard decision boundaries under such overlap suppresses shared evidence, biases feature representations, and ultimately undermines model reliability. To address this limitation, we propose Fuzzy Alignment with Comorbidity Topology FACT, a novel paradigm that reformulates MLD as a fuzzy alignment problem between atomic visual evidence and disease semantic anchors. FACT is characterized by three key features: (1) modeling visual polysemy through shared and reusable atomic visual evidence; (2) encoding disease correlation via semantic anchors structured by comorbidity topology; and (3) employing a metric-based fuzzy membership function for non-discriminative visual-semantic alignment. Extensive experiments on three public clinical benchmarks demonstrate that FACT consistently improves diagnostic performance while delivering clinically plausible predictions. The code will be available upon the acceptance of this paper.

Applications · Health / Medicine

Zelin Zang, WenZhe Li, Yongjie Xu, Chang Yu, Changxi Chi, Jingbo Zhou, Zhen Lei, Stan Z Li

In single-cell research, tracing and analyzing high-throughput single-cell differentiation trajectories is crucial for understanding biological processes. Key to this is the robust modeling of hierarchical structures that govern cellular development. Traditional methods face limitations in computational cost, performance, and stability. VAE-based approaches have made strides but still require branch-specific network modules, limiting their scalability and stability, while often suffering from posterior collapse. To overcome these challenges, we introduce HDTree, a generative modeling framework designed for robust lineage inference. HDTree captures tree relationships within a hierarchical latent space using a unified hierarchical codebook and employs a quantized diffusion process to model continuous cell state transitions. By aligning the generative process with the Waddington landscape, this method not only improves stability and scalability but also enhances the biological plausibility of inferred lineages. HDTree's effectiveness is demonstrated through comparisons on both general-purpose and single-cell datasets, where it outperforms existing methods in lineage inference accuracy, reconstruction quality, and hierarchical consistency. These contributions enable accurate and efficient modeling of cellular differentiation paths, offering reliable insights for biological discovery.

Applications · Health / Medicine

Yinbo Liu, Keyang Ye, Wenshan Sun, Handi Gao, Tian Tian

Reconstructing unified continuous dynamics from sparse, non-contiguous, and unpaired point cloud snapshots remains a fundamental challenge in spatiotemporal analysis for computer vision and developmental biology. Existing methods, including scene flow and Optimal Transport-based approaches, are limited either by explicit reliance on point-wise correspondences or by cumulative errors from frame-to-frame propagation and temporal discontinuity, and limited ability to model multi-attribute dynamics such as gene expression and population changes. We propose FlowCloud, a variational Neural Ordinary Differential Equation (Neural ODE) generative framework. FlowCloud aggregates information from all observed time points into a joint latent representation that initializes a Neural ODE $z(t)$ enabling continuous spatiotemporal evolution modeling while mitigating propagation-induced errors and preserving temporal consistency. Training is performed without predefined correspondences using a multi-faceted objective with complementary roles: Sinkhorn distance for global distribution alignment, Chamfer distance for local geometric consistency, trajectory regularization to encourage smooth and physically plausible dynamics, and supervised losses for multi-attribute prediction. Experiments on human motion and developmental biology datasets demonstrate improved interpolation accuracy and promising short-term extrapolation performance. By unifying geometry, attributes, and population dynamics within a continuous latent framework, FlowCloud offers a novel and robust solution for continuous dynamic reconstruction from unstructured spatiotemporal observations.

Applications · Health / Medicine

Josh Sun, Morteza Babaie, Wenyang hou, Mark Crowley, David Young

Antibody expression ranking is a critical task in antibody design, yet its modeling is severely hindered by the scarcity of labeled experimental data. To address this, we propose a unified preference-based learning framework that integrates scarce quantitative expression data with large-scale weak positive supervision from immunization data. We adapt Direct Preference Optimization (DPO) to protein language models by introducing a union-masked log-likelihood approximation and IMGT-based alignment, enabling efficient training on variable-length sequences. Evaluating on a diverse internal dataset of 1254 labeled sequences and 4 million unlabeled camelid-derived antibodies, we show that our method consistently outperforms baselines on most metrics. Our results demonstrate that preference learning can effectively learn from weak supervision, providing a scalable solution for antibody expressibility optimization in data-constrained settings.

Applications · Health / Medicine

Zhenglun Kong, Mufan Qiu, John Boesen, xiang lin, Sukwon Yun, Tianlong Chen, Manolis Kellis, Marinka Zitnik

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 novel spatially conditioned generative framework for predicting cell morphologies under perturbations. 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\%.

Applications · Health / Medicine

Danush Kumar Venkatesh, Adam Schmidt, Muhammad Abdullah Jamal, Omid Mohareri

Surgical video datasets are essential for scene understanding, enabling procedural modeling and intra-operative support. However, these datasets are often heavily imbalanced, with rare actions and tools under-represented, which limits the robustness of downstream models. We address this challenge with *SurgiFlowVid*, a sparse and controllable video diffusion framework for generating surgical videos of under-represented classes. Our approach introduces a dual-prediction diffusion module that jointly denoises RGB frames and optical flow, providing temporal inductive biases to improve motion modeling from limited samples. In addition, a sparse visual encoder conditions the generation process on lightweight signals (e.g., sparse segmentation masks or RGB frames), enabling controllability without dense annotations. We validate our approach on three surgical datasets across tasks including action recognition, tool presence detection, and laparoscope motion prediction. Synthetic data generated by our method yields consistent gains of $10$–$20$% over competitive baselines, establishing *SurgiFlowVid* as a promising strategy to mitigate data imbalance and advance surgical video understanding methods.

Applications · Health / Medicine

Bong Gyun Kang, JUNYONG AHN, Hyeongrok Han, Sungroh Yoon

Electronic Health Records (EHRs) possess unique characteristics distinct from natural language, yet existing EHR foundation models often rely on suboptimal NLP-based approaches. We propose a pretraining method tailored to EHRs' distinct features. First, we introduce Pathology-Focused Binning, a density-based quantization strategy that prioritizes clinically significant numerical ranges over usual values. Second, to jointly capture both the exact timing of clinical events and the relative intervals between them, we propose Dual-Calendar Rotary Positional Embedding (RoPE), which encodes absolute and relative temporal signals. Third, we introduce the Time-Conditioned Foreseeing (TCF) objective, aligning with clinical treatment planning to forecast events across multiple temporal horizons by explicitly modeling event timing. Our approach establishes a temporal generative EHR model that outperforms existing foundation models on nine diverse downstream tasks—achieving up to a 48% improvement in AUPRC—and enables the generation of realistic, temporally consistent patient trajectories.

Applications · Health / Medicine

Akira Nair, Jaehyun Joo, Jonghyun Lee, Lina Takemaru, Yidi Huang, Manu Shivakumar, Matthew Lee, Jaesik Kim, Sokratis Apostolidis, Dokyoon Kim

Genomic language models (gLMs) achieve strong performance across diverse genomic prediction tasks, but their internal biological representations remain poorly understood. Sparse autoencoders (SAEs) have emerged as an interpretability tool in vision and natural language models, yet their applicability to gLMs remains unexplored. We present a systematic study of SAE-based interpretability for gLMs, introducing a diverse benchmark of human genomic annotations and a suite of genome-tailored interpretability metrics. Using Evo2 as a primary case study, we show that SAE features, particularly those from intermediate layers, are more interpretable than raw model embeddings across 42/55 (76\%) of our genomic concept evaluations, with 26 of them having an F1 score greater than 0.7. We further find that interpretability depends on SAE training data properties such as evolutionary proximity and context length, with mixed-species and longer-context training improving recovery of human genomic features. Finally, we develop a graph-based representation method to construct a feature atlas that organizes semantically related genomic concepts learned by an SAE, outperforming the baseline approach of using SAE model weights. Our results establish SAEs as a powerful framework for better understanding gLMs, broadening their accessibility and utility for disease-driven genomic analysis.

Applications · Health / Medicine

Tan Pan, Shuhao Mei, Yixuan Sun, Kaiyu Guo, Chen Jiang, Zhaorui Tan, Mengzhu Li, LIMEI HAN, Xiang Zou, Yuan Cheng 等

Self-supervised pre-training methods in medical imaging typically treat each individual as an isolated instance, learning representations through augmentation-based objectives or masked reconstruction. They often do not adequately capitalize on a key characteristic of physiological features: anatomical structures maintain consistent spatial relationships across individuals (instances), such as the thalamus being medial to the basal ganglia, regardless of variations in brain size, shape, or pathology. We propose leveraging this cross-instance topological consistency as a supervisory signal. The challenge arises from the inherent variability in medical imaging, which can differ significantly across instances and modalities. To tackle this, we focus on two alignment regimes. (i) Intra-instance: with pixel-level correspondences available, a cross-modal triplet objective explicitly preserves local neighborhood topology. (ii) Inter-instance: without such supervision, we derive pseudo-correspondences to control partial neighborhood alignment and prevent topology collapse across modalities. We validate our approach across 7 downstream multi-modal tasks, achieving average improvements of 1.1\% and 5.94\% in segmentation and classification tasks, respectively, and demonstrating significantly better robustness when modalities are missing at test time.

Applications · Health / Medicine

Yishan Wang, Tsai-Ning Wang, Mathias Funk, Aaqib Saeed

Listening to heart and lung sounds — auscultation — is one of the first and most fundamental steps in a clinical examination. Despite being fast and non-invasive, it demands years of experience to interpret subtle audio cues. Recent deep learning methods have made progress in automating cardiopulmonary sound analysis, yet most are restricted to simple classification and offer little clinical interpretability or decision support. We present StethoLM, the first audio–language model specialized for cardiopulmonary auscultation, capable of performing instruction-driven clinical tasks across the full spectrum of auscultation analysis. StethoLM integrates audio encoding with a medical language model backbone and is trained on StethoBench, a comprehensive benchmark comprising 77,027 instruction–response pairs synthesized from 16,125 labeled cardiopulmonary recordings spanning seven clinical task categories: binary classification, detection, reporting, reasoning, differential diagnosis, comparison, and location-based analysis. Through multi-stage training that combines supervised fine-tuning and direct preference optimization, StethoLM achieves substantial gains in performance and robustness on out-of-distribution data. Our work establishes a foundation for instruction-following AI systems in clinical auscultation.

Applications · Health / Medicine

Yinhua Piao, Hyomin Kim, SEONGHWAN KIM, Yunhak Oh, Junhyeok Jeon, Sangyeon Hwang, Jaechang Lim, Woo Youn Kim, Chanyoung Park, Sungsoo Ahn

Predicting high-dimensional transcriptional responses to genetic perturbations is challenging due to severe experimental noise and sparse gene-level effects. Existing methods often suffer from mean collapse, where high correlation is achieved by predicting global average expression rather than perturbation-specific responses, leading to many false positives and limited biological interpretability. Recent approaches incorporate biological knowledge graphs into perturbation models, but these graphs are typically treated as dense and static, which can propagate noise and obscure true perturbation signals. We propose AdaPert, a perturbation-conditioned framework that addresses mean collapse by explicitly modeling sparsity and biological structure. AdaPert learns perturbation-specific subgraphs from biological knowledge graphs and applies adaptive learning to separate true signals from noise. Across multiple genetic perturbation benchmarks, AdaPert consistently outperforms existing baselines and achieves substantial improvements on DEG-aware evaluation metrics, indicating more accurate recovery of perturbation-specific transcriptional changes.

Applications · Health / Medicine

Binghao Liu, Wenzheng Zhao, Zhijie Zheng, Fei Gu

Effective DNA modeling demands the integration of complex patterns such as local motifs, long-range dependencies, and periodic signals. Yet, architectures like CNNs, Transformers, and SSMs are hindered by static or time-domain-exclusive designs, which limit their representational flexibility. To address this, we introduce the **Synergistic Plasticity Unit (SPU)**, a scalable architecture that achieves multi-level plasticity through three synergistic layers. Specifically, SPU integrates a *Locus Plasticity Layer* (LPL) to capture fine-grained local motifs via token-specific convolution operations, while utilizing a *Domain Plasticity Layer* (DPL) to form multi-domain global features by concurrently modeling sequential (time) and spectral (frequency) patterns. Furthermore, it incorporates a *Saliency Plasticity Layer* (SPL) to optimize information flow through dual-axis saliency scoring. Supported by theoretical analysis, extensive empirical validation, and in-depth biological interpretation, this unified design enables SPU to achieve state-of-the-art performance with quasi-linear complexity, establishing a robust and principled paradigm for DNA modeling. Code will be available upon acceptance.

Applications · Health / Medicine

Boqiang Xu, Wei Zhang, Ding Ma, Jian Liang, Zhenan Sun, Zhen Lei

Operating room (OR) scene graph generation (SGG) enables holistic modeling of OR domains by encoding interactions among medical staff, tools, and equipment as triplet-based structured scene graphs. Although existing OR SGG methods demonstrate satisfactory overall performance, they exhibit substantially lower accuracy on long-tail categories compared to head categories in OR data. We introduce SGG-ICL, a novel framework that represents the first attempt to address the long-tail problem in OR SGG by leveraging in-context learning (ICL). SGG-ICL first identifies long-tail samples via an Adaptive Router module and selectively applies ICL only to these samples. This selective routing strategy enhances performance on long-tail categories without degrading head-category accuracy. Subsequently, SGG-ICL constructs a candidate pool through multimodal retrieval and then employs a trained MLLM Reranker to re-rank the candidates, selecting the most similar examples to the test sample for ICL. The reranker is supervised by IoU scores derived from annotated SGG triplets and exploits rich multimodal information to estimate pairwise sample similarity. Experimental results show that SGG-ICL improves accuracy on long-tail categories by 6.9%, while also achieving a 2.6% improvement in overall accuracy.

Applications · Health / Medicine

Jun Li, ZIWEI QIN

Semi-supervised learning has become a dominant paradigm for reducing annotation costs. However, we argue that the current progress is clouded by a dual problem of overconfidence. Algorithmically, prevailing pseudo-labeling frameworks often conflate prediction confidence with uncertainty, leading to severe confirmation bias and poorly calibrated models. Methodologically, since multiple benchmark datasets lack validation sets, some studies repurpose test sets as validation sets, leading to inflated results. Subsequent methods, compelled to employ the same strategy to surpass reported SOTA, trigger an arms race of overfitting. Exciting numerical gains may reflect test overfitting rather than genuine progress. Thus, we propose TCSeg, a tri-space calibrated segmentation framework founded on a principled dual-axis reliability assessment engine. It explicitly decouples confidence from uncertainty and uses this signal to detect and correct confirmation bias across feature, probability, and image spaces in a collaborative manner. Across three benchmarks, TCSeg delivers consistently strong performance at both the best and final checkpoints, and we report results under a multi-run protocol to reset the benchmark with a more realistic perspective. Core code is available: https://github.com/BubbleDirk/temporary_anonymous_tcseg.

Applications · Health / Medicine

Ziyuan Gao

Medical image segmentation faces a fundamental challenge in continual learning: data arrives sequentially from heterogeneous sources, yet effective continual learning requires discovering which tasks share sufficient structure to benefit from joint learning. Existing methods either apply uniform constraints across all tasks, causing catastrophic forgetting when tasks conflict, or require predefined task groupings that cannot anticipate future task diversity. We introduce MedCRP-CL, a framework that performs online task structure discovery and structure-aware continual learning. Leveraging the Chinese Restaurant Process (CRP), our method dynamically infers task groupings from clinical text prompts as tasks arrive, without requiring predefined cluster counts or access to future tasks. We term these discovered groupings semantic modalities, as they capture finer-grained structure than physical imaging modalities by integrating anatomical region and pathological context. Guided by this discovered structure, we maintain semantic modality-specific LoRA adapters regularized by intra-modality EWC, ensuring parameter isolation across dissimilar task groups while facilitating knowledge transfer within similar ones. The framework is also replay-free, storing only aggregate statistics rather than raw patient data. Experiments on 16 medical segmentation tasks across four imaging modalities demonstrate that MedCRP-CL achieves 73.3\% Dice score with only 4.1\% forgetting, outperforming the best baseline by 8.0\% while requiring 6$\times$ fewer parameters. Code is provided as supplemental material for review and will be publicly released upon acceptance.

Applications · Health / Medicine

Qi Chen, Shuhan Ding, Yu Gu, Nan Liu, Jiang Bian, Alan Yuille, Zongwei Zhou, Jingjing Fu

Variational autoencoders (VAEs) compress high resolution CT volumes into compact latents while preserving clinically relevant structure. However, training CT-specific VAEs from scratch or heavily fine-tuning them incurs substantial computational and engineering cost, and often degrades under heterogeneous scanners, protocols, and diseases. This paper makes a progressive stride toward training-free medical VAEs by leveraging a critical observation: a single Foundation VAE, pretrained at scale on natural images and videos, can serve as a unified interface for CT Reconstruction, Augmentation, and Generation. With both encoder and decoder frozen, the Foundation VAE reconstructs CT volumes with preserved anatomy while suppressing acquisition noise; training segmentation models on these reconstructions improves surface accuracy by 3.9\% NSD on average for pancreatic tumor and lung tumor. Within the same Foundation VAE latent space, a conditional latent diffusion model achieves 3.9\% lower average FVD with 36.2\% higher CT CLIP score, and improves multi-disease generation faithfulness across 18 types by 2.76\% AUC. These results demonstrate Foundation VAEs as a practical interface for scalable CT representation reuse and faithful CT generation.