论文检索

Applications · Health / Medicine

Dian Ding, Liren Dong, Yu Lu, Juntao Zhou, Ran Wang, Peng Li, Zhenyi Jia, Guangtao Xue

Gastrointestinal (GI) motility assessment via bowel sounds (BS) offers a non-invasive alternative to resource-intensive clinical standards. However, the diagnostic utility of BS is often compromised by its spectral overlap with non-stationary speech interference. While generative models have advanced signal restoration, traditional Gaussian-based diffusion frameworks struggle with the impulsive, heavy-tailed nature of real-world clinical noise. In this paper, we propose a novel Cauchy-driven Diffusion Bridge framework to isolate high-fidelity bowel sounds from complex interference. Our contributions are three-fold: (1) We introduce ClinBS, a large-scale clinical dataset (over 25 hours) containing rare pathological transients verified by experts; (2) We mathematically formulate a Cauchy bridge driver, deriving closed-form expressions for the score and density to better model heavy-tailed perturbations; and (3) We implement an efficient sampling procedure via Gaussian scale-mixture reparameterization. Extensive experiments show our framework achieves state-of-the-art performance, outperforming baselines by 13.4%–49.8% across core metrics and elevating abnormal BS recognition accuracy to 88.01%. These results demonstrate the system's potential for robust clinical GI monitoring and diagnosis.

Applications · Health / Medicine

Xiaoda Wang, Ching Chang, Defu Cao, Kaiqiao Han, Fang Sun, Yue Huang, Minxiao Wang, Chang Xu, Xiao Luo, Runze Yan 等

Physiological waveforms (e.g., ECG, PPG, EEG) encode clinically meaningful information in fine-grained morphology, precise timing, and cross-channel dynamics, yet most machine learning systems still treat them as generic time series and optimize end-to-end prediction. In this position paper, **we argue for verifiable physiological waveform reasoning: extracting localized, measurable signal evidence from raw signals, interpreting that evidence into physiological semantics, and supporting clinically grounded decisions.** Waveform reasoning is challenging due to acquisition heterogeneity, signal fidelity, complex semantics and cross-channel coupled dynamics. We analyze why existing model families remain insufficient: physiological foundation models learn strong perceptual representations but remain weak at verifiable reasoning, while LLM-based adaptations have limited waveform understanding. To bridge this gap, **we advocate verifiable, closed-loop systems that unify waveform semantics with language intelligence.** Concretely, we propose a dual-process architecture that System 1 aligns physiological waveforms with language, and System 2 provides agentic reasoning via a Plan--Act--Verify loop, together enabling verifiable physiological waveform reasoning. We further propose evaluations beyond accuracy, emphasizing traceability, replayability, counterfactual robustness, and calibrated abstention.

Applications · Health / Medicine

Anton Thiel, Chris P Barnes, Angus Cunningham

Reinforcement learning has driven the mass adoption of large language models by unlocking unexpected capabilities, yet this approach remains largely underexplored for generative DNA models. We investigate whether similar post-training techniques can induce emergent biological realism in DNA language models, using plasmid generation as a testbed due to plasmids' relative simplicity, well-characterized functional constraints, and ubiquity in biotechnology. Using Group Relative Policy Optimization with a reward function based on constraints from engineered biology, our model achieves a 77\% quality control pass rate compared to 5\% for the pretrained baseline. Remarkably, beyond explicitly optimized features, the model exhibits surprising biological parallels: generated sequences match natural plasmids in thermodynamic stability, codon usage patterns, and ORF length distributions, properties not explicitly optimized in the reward function. These results suggest that RL post-training can steer DNA language models toward biologically coherent regions of sequence space, analogous to how such techniques unlock unexpected capabilities in natural language models, particularly in verifiable domains.

Applications · Health / Medicine

Zaikang Lin, Sei Chang, Aaron Zweig, Minseo Kang, Fabian Theis, Elham Azizi, David A Knowles

Modern high-throughput biological datasets containing thousands of perturbations enable large-scale discovery of causal graphs that represent regulatory interactions between genes. Differentiable causal graphical models and regression-based methods have been developed to infer gene regulatory networks (GRNs) from interventional datasets. However, existing approaches fail to capture the non-linear dynamics of biological processes such as cellular differentiation. To address this limitation, we propose \textit{PerturbODE}, a novel framework that employs interpretable neural ordinary differential equations (neural ODEs) to model cell state trajectories under perturbations and derive the underlying causal GRN from the neural ODE parameters, enabling downstream simulation of unseen genetic interventions. The GRN is encoded via a single-hidden-layer feedforward network, implicitly grouping genes into interpretable co-regulated modules. We demonstrate PerturbODE's efficacy in GRN inference and extension to perturbation response prediction across both simulated and real overexpression datasets.

Applications · Health / Medicine

Julong Yang, Wen Huang, Junhui Chen, Jian Peng

Recent advances in diffusion models show promise for Structure-Based Drug Design (SBDD), which aims to generate 3D ligand molecules that bind tightly to specific protein targets. This involves jointly optimizing the ligand's 3D conformation and its binding position within the protein pocket. However, existing diffusion-based SBDD methods diffuse conformation and binding position simultaneously within a high-dimensional joint space, leading to inefficient exploration and suboptimal generation quality in both aspects. To address this, we propose **DeCoDe**, a novel diffusion framework that **decouples** the diffusion processes of the binding position and molecular conformation. Our key insight is to prioritize the perturbation of the ligand's internal conformation in the early stages of the forward (noising) process, while accelerating the perturbation of its global binding position later. This design guides the reverse (denoising) process to *first coarsely position* the ligand within the pocket before \textit{refining its detailed structure}, mimicking a more efficient, step-wise generation strategy. Extensive experiments on the CrossDocked2020 benchmark show that DeCoDe achieves significantly higher structural fidelity (with an average improvement of 18%), while maintaining competitive binding affinity and overall molecular properties compared to state-of-the-art baselines. Code will be released after acceptance.

Applications · Health / Medicine

Bosong Huang, Panzhen Zhao, Zengxiang Li, Patricia Lee, Wei Jin, Alan Liew, Ming Jin, Shirui Pan

Electrocardiography (ECG) is a cornerstone of cardiac assessment, making the learning of informative ECG representations fundamental to tasks ranging from disease diagnosis to clinical report generation. However, existing methods operate almost exclusively in the observable ECG signal space. In practice, the standard twelve-lead ECG represents multiple projections of the same underlying cardiac electrical activity from different spatial orientations. Therefore, representation learning in the ECG space inevitably introduces substantial redundancy, which may lead to spurious correlations and increased risk of overfitting. To address this and motivated by the Frank vectorcardiogram (VCG) model, we propose learning a unified latent representation of cardiac electrical activity directly in the VCG space. We introduce LVCG, the first general self-supervised representation learning framework designed to operate in this physically grounded latent space. By learning view-invariant latent VCG representations rather than lead-specific artifacts, VCG minimizes redundancy and improves generalization. LVCG generally outperforms ECG-space baselines across tasks, demonstrating enhanced robustness and generalization, especially in domain shift settings. Our code has been made available at https://anonymous.4open.science/r/LVCG-A0C4

Applications · Health / Medicine

Shaohao Rui, Kaitao Chen, Weijie Ma, Xiaosong Wang

Extended Chain-of-Thought (CoT) reasoning has significantly bolstered the capabilities of medical large language models (LLMs). However, current models exhibit static computational expenditure, applying lengthy reasoning processes indiscriminately to both simple queries and complex diagnostic cases. This inefficiency is particularly prohibitive in real-world healthcare, where clinical scenarios range from time-sensitive emergencies requiring rapid response to intricate pathologies demanding deep analysis. To address this, we propose **AdaThink-Med**, an end-to-end framework for adaptive reasoning via uncertainty-guided length calibration. Although the underlying mechanism is generalizable, we demonstrate its critical value in the medical domain, where balancing inference latency with diagnostic precision is paramount. AdaThink-Med leverages entropy-based uncertainty estimation within reinforcement fine-tuning to dynamically shape reward signals: it penalizes verbosity for high-confidence correct answers (e.g., straightforward knowledge retrieval) while incentivizing extended exploration for uncertain or ambiguous scenarios. Across six medical benchmarks, AdaThink-Med reduces inference token consumption by $4.7\times$ to $6.4\times$ on Qwen and Llama architectures, respectively, with minimal performance trade-offs. Notably, the model spontaneously develops distinct "non-thinking'' and "thinking'' modes, demonstrating an autonomous ability to allocate computational resources efficiently based on clinical urgency and complexity.

Applications · Health / Medicine

Zeyu An, Wanyu LIN

{\em De novo} peptide sequencing is a pivotal technique that directly reconstructs amino acid sequences from tandem mass spectrometry (MS/MS) data; it enables the identification of novel proteins and variants absent from reference databases. Previous methods are typically based on autoregressive (AR) decoding or one-shot generation. The AR-based methods conflict with the bidirectional and globally constrained nature of MS/MS evidence and inevitably accumulate errors, while one-shot generation does not explicitly enforce physical constraints, failing to produce chemically valid and reliable peptides in a single pass. Accurate sequencing necessitates reasoning over the entire peptide simultaneously, enabling iterative self-correction under global constraints. To this end, we introduce $\textbf{PhysNovo}$, a novel paradigm that harnesses discrete diffusion to enable simultaneous global reasoning and iterative refinement. Specifically, PhysNovo reformulates sequencing as a $\textbf{phys}$ically mass-constrained reasoning process by embedding a knapsack-based feasibility kernel to enforce exact precursor mass consistency. By conditioning the diffusion process on global spectral context, PhysNovo supports abductive reasoning where bidirectional evidence is exploited to iteratively resolve local inconsistencies and ensure physically valid predictions. PhysNovo achieves state-of-the-art performance, exceeding baselines by over 2\% in precision, with larger gains on out-of-distribution data.

Applications · Health / Medicine

Mehmet Yigit Balik, Harri Lähdesmäki

Single-cell RNA sequencing provides insights into gene expression at single-cell resolution, yet inferring temporal processes from these static snapshot measurements remains a fundamental challenge. Current approaches utilizing neural differential equations and flows are sensitive to overfitting and lack careful considerations of biological variability. In this work, we propose a generative framework that models population trends using a latent heteroscedastic Gaussian process (GP) approximated by Hilbert space methods. To address the absence of genuine cell trajectories, we leverage an optimal transport (OT) objective that aligns generated and observed population distributions. Our method explicitly captures biological heterogeneity by incorporating cell-specific latent time and cell type conditioning to disentangle temporal asynchrony and trajectories to different cell types. We demonstrate state-of-the-art performance on complex interpolation and extrapolation benchmarks and introduce a novel gradient-based strategy for inferring perturbation trajectories.

Applications · Health / Medicine

Silas Ruhrberg Estevez, Chris Chiu, Mihaela van der Schaar

Modern clinical practice relies on evidence-based guidelines implemented as compact scoring systems composed of a small number of interpretable decision rules. While machine-learning models achieve strong performance, many fail to translate into routine clinical use due to misalignment with workflow constraints such as memorability, auditability, and bedside execution. We argue that this gap arises not from insufficient predictive power, but from optimizing over model classes that are incompatible with guideline deployment. Deployable guidelines often take the form of unit-weighted clinical checklists, formed by thresholding the sum of binary rules, but learning such scores requires searching an exponentially large discrete space of possible rule sets. We introduce $\texttt{AgentScore}$, which performs semantically guided optimization in this space by using LLMs to propose candidate rules and a deterministic, data-grounded verification-and-selection loop to enforce statistical validity and deployability constraints. Across eight clinical prediction tasks, $\texttt{AgentScore}$ outperforms existing score-generation methods and achieves AUC comparable to more flexible interpretable models despite operating under stronger structural constraints. On two additional externally validated tasks, $\texttt{AgentScore}$ achieves higher discrimination than established guideline-based scores.

Applications · Health / Medicine

Yipan Wei, Wenke Huang, Yapeng Li, He Li, Qixin Zhang, Mang Ye, Bo Du

Federated Prompt Learning (FPL) adapts Vision-Language Models to privacy-sensitive medical imaging, typically via a textual tuning paradigm that assumes the frozen visual encoder provides a discriminative feature geometry. We argue this assumption breaks down in medical settings, leading to two geometric pathologies: (1) Intra-client: Medical Manifold Collapse, where high morphological similarity reduces the effective rank of visual features; and (2) Inter-client: Medical Topological Misalignment, where heterogeneous acquisition protocols induce inconsistent geometry across clients. To address these, we propose FedMAP, which shifts the paradigm to Visual Manifold Anchoring. FedMAP utilizes an LLM-derived codebook as a client-invariant synchronization signal to restructure the visual space, via Manifold Semantic Anchoring (MSA) and Topology Structural Alignment (TSA) to enforce consistent inter-class relations. Experiments on FedISIC, FedCamelyon17, and a private ultrasound dataset show that FedMAP consistently outperforms state-of-the-art methods, especially in high-noise regimes where manifold collapse is most severe.

Applications · Health / Medicine

Marta Hasny, Laura Daza, Keno Bressem, Maxime Di Folco, Julia Schnabel

Large-scale medical biobanks provide imaging data complemented by extensive tabular information, such as clinical measurements or demographics. However, this abundance of tabular attributes does not reflect real-world datasets, where only a subset of attributes may be available. This discrepancy calls for methods that remain robust to missing values at inference. To address this challenge, we propose RoVTL (Robust Vision-Tabular Learning), a framework designed to handle any level of tabular data availability, from 0% to 100%. RoVTL comprises two key stages: contrastive pretraining, where we introduce tabular attribute missingness as data augmentation to promote robustness, and downstream task tuning, where tabular missingness is complemented by a novel Tabular More vs. Fewer loss that ranks performance based on the amount of available tabular data. Combined with gated-cross attention fusion module, our tuning approach enables consistent performance across all tabular data completeness scenarios. We evaluate RoVTL on cardiac MRI scans from the UK Biobank, demonstrating superior robustness to missing tabular data compared to prior methods. Furthermore, RoVTL successfully generalizes to an external cardiac MRI dataset for multimodal disease classification, and extends to the natural images domain, achieving robust performance on a car advertisements dataset. Model weights and code will be released.

Applications · Health / Medicine

Chenhe Du, Xuanyu Tian, Qing Wu, Muyu Liu, Jingyi Yu, Hongjiang Wei, Yuyao Zhang

Plug-and-Play diffusion prior (PnPDP) frameworks have emerged as a powerful paradigm for solving imaging inverse problems by treating pretrained generative models as modular priors. However, we identify a critical flaw in prevailing PnP solvers (e.g., based on HQS or Proximal Gradient): they function as memoryless operators, updating estimates solely based on instantaneous gradients. This lack of historical tracking inevitably leads to non-vanishing steady-state bias, where the reconstruction fails to strictly satisfy physical measurements under heavy corruption. To resolve this, we propose **Dual-Coupled PnP Diffusion**, which restores the classical dual variable to provide integral feedback, theoretically guaranteeing asymptotic convergence to the exact data manifold. However, this rigorous geometric coupling introduces a secondary challenge: the accumulated dual residuals exhibit spectrally colored, structured artifacts that violate the Additive White Gaussian Noise (AWGN) assumption of diffusion priors, causing severe hallucinations. To bridge this gap, we introduce Spectral Homogenization (SH), a frequency-domain adaptation mechanism that modulates these structured residuals into statistically compliant pseudo-AWGN inputs. This effectively aligns the solver's rigorous optimization trajectory with the denoiser's valid statistical manifold. Extensive experiments on CT and MRI reconstruction demonstrate that our approach resolves the bias-hallucination trade-off, achieving state-of-the-art fidelity with significantly accelerated convergence.

Applications · Health / Medicine

Keunho Byeon, Jin Tae Kwak

Spatial transcriptomics offers spatially resolved gene expression profiling within tissue sections, but its cost and limited throughput hinder large-scale deployment. To extend this capability to routine practice, recent computational methods aim to infer spatial gene expression directly from ubiquitous hematoxylin and eosin-stained histology slides. However, most existing models assume Cartesian or geometry-agnostic locality, despite the hexagonal sampling of widely used spot-array platforms, and point-wise regression objectives often yield over-smoothed gene expression profiles, obscuring gene-specific spatial heterogeneity. To address these, we propose HEXST, a geometry-aligned Transformer for spatial gene expression prediction from histology. HEXST operates directly on hexagonal spot coordinates to enable efficient local-to-global contextual modeling via tailored shifted-window attention mechanism and hexagonal rotary positional encoding. To enhance gene-wise spatial contrast, HEXST complements point-wise regression with a contrast-sensitive differential objective and transcriptomic priors from a pretrained single-cell foundation model during training. Across seven spatial transcriptomics datasets, HEXST consistently outperforms state-of-the-art models, providing accurate and robust spatial gene expression predictions while preserving gene-wise contrast and spatial heterogeneity.

Applications · Health / Medicine

John Wu, Yongda Fan, Zhenbang Wu, Paul Landes, Eric Schrock, Sayeed Sajjad Razin, Arjun Chatterjee, Naveen Baskaran, Joshua Steier, Andrea Fitzpatrick 等

Difficulty replicating baselines, high computational costs, and required domain expertise create persistent barriers to clinical AI research. To address these challenges, we introduce PyHealth 2.0, an enhanced clinical deep learning toolkit that enables predictive modeling in as few as 7 lines of code. PyHealth 2.0 offers three key contributions: (1) a comprehensive toolkit addressing reproducibility and compatibility challenges by unifying 15+ datasets, 20+ clinical tasks, 25+ models, 5+ interpretability methods, and uncertainty quantification including conformal prediction within a single framework that supports diverse clinical data modalities—signals, imaging, and electronic health records—with translation of 5+ medical coding standards; (2) accessibility-focused design accommodating multimodal data and diverse computational resources with up to 39× faster processing and 20× lower memory usage, enabling work from 16GB laptops to production systems; and (3) an active open-source community of 400+ members lowering domain expertise barriers through extensive documentation, reproducible research contributions, and collaborations with academic health systems and industry partners, including multi-language support via RHealth. PyHealth 2.0 establishes an open-source foundation and community advancing accessible, reproducible healthcare AI.

Applications · Health / Medicine

Weimin Wu, Xuefeng Song, Yibo Wen, Qinjie Lin, Zhihan Zhou, Jerry Yao-Chieh Hu, Zhong Wang, Han Liu

We introduce Genome-Factory, the first integrated Python library for tuning, deploying, and interpreting genomic foundation models. Our core contribution is to simplify and unify the workflow for genomic model development: data collection, model tuning, inference, benchmarking, and interpretability. For data collection, Genome-Factory offers an automated pipeline to download genomic sequences and preprocess them. It also includes quality control like GC content normalization. For model tuning, Genome-Factory supports three approaches: full-parameter, low-rank adaptation, and adapter-based fine-tuning. It is compatible with a wide range of genomic models. For inference, Genome-Factory enables both embedding extraction and DNA sequence generation. For benchmarking, we include two existing benchmarks and provide a flexible interface for users to incorporate additional benchmarks. For interpretability, Genome-Factory introduces the first open-source biological interpreter based on a sparse auto-encoder. This module disentangles embeddings into sparse, near-monosemantic latent units and links them to genomic features by regressing on external readouts. To improve accessibility, Genome-Factory offers a zero-code command-line and a user-friendly web interface. We validate the utility of Genome-Factory across three dimensions: (i) Compatibility with diverse models and fine-tuning methods; (ii) Benchmarking downstream performance using two open-source benchmarks; (iii) Biological interpretation of learned representations with DNABERT-2. These results highlight its practical value for real-world genomic analysis.

Applications · Health / Medicine

Noah Flynn

Designing genetic circuits, which are biological systems capable of programmed behaviors within living cells, remains a laborious, expert-driven process despite decades of progress in synthetic biology. We introduce GenCircuit-RL, a reinforcement learning framework that trains language models to reason about genetic circuit design through code generation, where models produce Python code using PySBOL to construct circuits in the standardized Synthetic Biology Open Language (SBOL) format. Our approach addresses the challenge of sparse feedback in biological design through hierarchical verification rewards that decompose correctness into five levels, from code execution through structural validity to functional behavior, providing dense learning signal while multiplicative dependencies prevent reward hacking. We contribute SynBio-Reason, a benchmark of approximately 4,753 circuits spanning six canonical circuit types and nine tasks from code repair to de novo design, with held-out biological parts enabling rigorous out-of-distribution evaluation. A four-stage curriculum progressively shifts optimization pressure from basic code generation toward functional correctness, enabling models to acquire compositional reasoning capabilities incrementally. Our framework demonstrates that hierarchical verification combined with curriculum learning enables compact language models to generate functionally correct genetic circuits, including generalization to novel biological parts and rediscovery of canonical designs from synthetic biology literature.

Applications · Health / Medicine

Jiahao Kuang, Nuowei Liu, Changzhi Sun, Jie Wang, Tao Ji, Yuanbin Wu

Function-guided protein design is a crucial task with significant applications in drug discovery and enzyme engineering. However, the field lacks a unified and comprehensive evaluation framework. Current models are assessed using inconsistent and limited subsets of metrics, which prevents fair comparison and a clear understanding of the relationships between different evaluation criteria. To address this gap, we introduce **PDFBench**, the first comprehensive benchmark for function-guided de novo protein design. Our benchmark systematically evaluates eight state-of-the-art models on 16 metrics across two key settings: description-guided design, for which we repurpose the Mol-Instructions dataset, originally lacking quantitative benchmarking, and keyword-guided design, for which we introduce a new test set, SwissTest, created with a strict datetime cutoff to ensure data integrity. By benchmarking across a wide array of metrics and analyzing their correlations, **PDFBench** enables more reliable model comparisons and provides key insights to guide future research.

Applications · Health / Medicine

Yaoyu Chen, Xiaoli Lin, Ziyi Gong, Jun Pang

Efficiently designing high-quality molecules targeting disease-relevant targets is a critical challenge. Most existing methods can capture pairwise amino acid relations, neglecting the higher-order relations among multiple amino acids. This paper proposes a target-specific molecule generation framework, namely TSMGen, to comprehensively capture the local and global structural information of the protein pocket by modeling higher-order spatial dependencies both at the atomic and the amino acid levels. Furthermore, we design a context-aware bidirectional fusion module to learn the more detailed structural information about the protein pocket. This module simultaneously attends to features from both the protein pocket and the molecule, fully leveraging the structural information from both to optimize the generation process of targeted molecules, thereby enhancing the quality of generated molecules. Experiments show that TSMGen outperforms state-of-the-art methods in terms of Vina Score, High Affinity, QED, SA and Diversity, and a case study on $\beta$-secretase enzyme further confirms its ability to generate molecules with stronger binding affinity.

Applications · Health / Medicine

Kaitao Chen, Weiqian Zhao, Jiamin Wu, Qihao Zheng, Shangquan Sun, Chunfeng Song, Xiaosong Wang, Mu Zhou, Mianxin Liu

Vision-language models (VLMs) combining reinforcement learning (RL) ignite remarkable progress in multimodal reasoning, yet still struggle with medical images, which typically exhibit extremely sparse visual evidence to inform clinical decision-making. We recognize that pruning visual tokens outside the grounding region greatly enhances medical reasoning. However, a united RL framework for active visual token pruning (VTP) and medical multimodal reasoning remains unestablished. Here, we propose a dual-stream RL framework, ViToS, to fulfill token pruning and question answering. ViToS trains one policy model with two task branches, where one focuses on grounding while the other conducts token-sparse reasoning after VTP. Furthermore, we solve the coupled policy learning problem by introducing the cross-feedback sequential optimization, avoiding gradient conflict and facilitating convergence of the shared policy model. Evaluated on seven medical benchmarks, our method reduces visual tokens to 77\% of the original sequence length while achieving a 108.27\% relative performance on Lingshu-7B and 104.16\% relative performance on HuatuoGPT-Vision-7B. Overall, ViToS delivers superior performance and inference speedup, establishing an efficient paradigm for medical multimodal reasoning.