论文检索

Applications · Health / Medicine

Pengfei Hu, Chang Lu, Feifan Liu, Yue Ning

Deep learning models for clinical event prediction on electronic health records (EHR) often suffer performance degradation when deployed under different data distributions. While domain adaptation (DA) methods can mitigate such shifts, its "black-box" nature prevents widespread adoption in clinical practice where transparency is essential for trust and safety. We propose ExtraCare to decompose patient representations into invariant and covariant components. By supervising these two components and enforcing their orthogonality during training, our model preserves label information while exposing domain-specific variation at the same time for more accurate predictions than most feature alignment models. More importantly, it offers human-understandable explanations by mapping sparse latent dimensions to medical concepts and quantifying their contributions via targeted ablations. ExtraCare is evaluated on two real-world EHR datasets across multiple domain partition settings, demonstrating superior performance along with enhanced transparency, as evidenced by its accurate predictions and explanations from extensive case studies.

Applications · Health / Medicine

Haoran Zhang, Hyewon Jeong, Olawale Salaudeen, Walter Gerych, Nigam Shah, Marzyeh Ghassemi

Despite large language models (LLMs) achieving impressive performance on benchmark tasks such as medical question answering, their real-world utility remains limited. We argue that while benchmarks play a valuable role in developing methods and filtering promising models during development, they often tell us very little about deployment readiness. Many health AI systems with strong retrospective accuracy have failed in practice, while others with modest benchmark performance have demonstrated meaningful clinical benefits. We detail the limitations of benchmark-centric evaluations of deployment readiness. We argue that we should only use benchmarks to find candidate methods or models, not to justify deployment. We call for increased use of prospective studies and policy changes that align incentives with clinically grounded evaluation.

Applications · Health / Medicine

Aryan Pedawi, Jordi Silvestre-Ryan, Bradley Worley, Darren Hsu, Kushal Shah, Elias Stehle, Jingrong Zhang, Izhar Wallach

Make-on-demand combinatorial synthesis libraries (CSLs) like Enamine REAL have significantly enabled drug discovery efforts. However, their large size presents a challenge for virtual screening, where the goal is to identify the top compounds in a library according to a computational objective (e.g., optimizing docking score) subject to computational constraints under a limited computational budget. For current library sizes---numbering in the tens of billions of compounds---and scoring functions of interest, a routine virtual screening campaign may be limited to scoring fewer than 0.1% of the available compounds, leaving potentially many high scoring compounds undiscovered. Furthermore, as constraints (and sometimes objectives) change during the course of a virtual screening campaign, existing virtual screening algorithms typically offer little room for amortization. We propose the approximate-but-exhaustive search protocol for CSLs, or APEX. APEX utilizes a neural network surrogate that exploits the structure of CSLs in the prediction of objectives and constraints to make full enumeration on a consumer GPU possible in under a minute, allowing for exact retrieval of approximate top-k sets. To demonstrate APEX's capabilities, we develop a benchmark CSL comprised of more than 10 million compounds, all of which have been annotated with their docking scores on five medically relevant targets along with physicohemical properties measured with RDKit such that, for any objective and set of constraints, the ground truth top-k compounds can be identified and compared against the retrievals from any virtual screening algorithm. We show APEX's consistently strong performance both in retrieval accuracy and runtime compared to alternative methods.

Applications · Health / Medicine

Pengtao Xie, Victor Nizet, Lei Wang, Ahmed Alaa, Daniel Zielinski, Trey Ideker, Bernhard Palsson

Understanding the functions of DNAs, RNAs, and proteins is fundamental to advancing life science research and enabling translational applications such as drug discovery and precision medicine. While deep learning methods have shown promise in biomolecular function prediction, they typically constrain outputs to predefined categories and require training separate models for each task. Existing multi-task learning methods operate on a fixed set of predefined tasks and require model retraining when new tasks arise. Furthermore, current approaches produce one-shot, static outputs, lacking the capacity for iterative refinement or deeper exploration of predictions. This position paper argues that multi-modal large language models (LLMs) are essential for enabling free-form and interactive prediction of biomolecular functions, and zero-shot generalization to new tasks without model retraining. These models can generate coherent and context-aware text outputs that reflect the complexity and nuance of diverse functional roles. Importantly, they can generalize to novel biomolecules whose functions are unknown or poorly characterized, and they enable generalization to new tasks through prompt-driven adaptation, eliminating the need for task-specific retraining. Additionally, multi-modal LLMs enable interactive, multi-turn dialogue, allowing users to iteratively refine queries, clarify contexts, and explore hypotheses in a dynamic and responsive manner. By leveraging these capabilities, multi-modal LLMs provide a scalable, adaptable, and generalizable framework for advancing biomolecular function prediction and accelerating biological discovery.

Applications · Health / Medicine

Ioannis Anagnostides, Itai Zilberstein, Zachary Sollie, Arman Kilic, Tuomas Sandholm

The allocation of scarce donor organs constitutes one of the most consequential algorithmic challenges in healthcare. While the field is rapidly transitioning from rigid, rule-based systems to machine learning and data-driven optimization, we argue that current approaches often overlook a fundamental barrier: incentives. In this position paper, we highlight that organ allocation is not merely an optimization problem, but rather a complex game involving organ procurement organizations, transplant centers, clinicians, patients, and regulators. Focusing on US adult heart transplant allocation, we identify critical incentive misalignments across the decision-making pipeline, and present data showing that they are having adverse consequences today. Our main position is that the next generation of allocation policies should be incentive aware. We outline a research agenda for the machine learning community, calling for the integration of mechanism design, strategic classification, causal inference, and social choice to ensure robustness, efficiency, fairness, and trust in the face of strategic behavior from the various constituent groups.

Applications · Health / Medicine

Huimin Yan, Liang Bai, Xian Yang, Long Chen

Most existing CLIP-style medical vision--language pretraining methods rely on global or local alignment with substantial paired data. However, global alignment is easily dominated by non-diagnostic information, while local alignment fails to integrate key diagnostic evidence. As a result, learning reliable diagnostic representations becomes difficult, which limits their applicability in medical scenarios with limited paired data. To address this issue, we propose an LLM-Guided Diagnostic Evidence Alignment method (LGDEA), which shifts the pretraining objective toward evidence-level alignment that is more consistent with the medical diagnostic process. Specifically, we leverage LLMs to extract key diagnostic evidence from radiology reports and construct a shared diagnostic evidence space, enabling evidence-aware cross-modal alignment and allowing LGDEA to effectively exploit abundant unpaired medical images and reports, thereby substantially alleviating the reliance on paired data. Extensive experimental results demonstrate that our method achieves consistent and significant improvements on phrase grounding, image--text retrieval, and zero-shot classification, and even rivals pretraining methods that rely on substantial paired data.

Applications · Health / Medicine

Yuanlin Yang, Chenhui Li, Xuhao Guo, ANQI ZHANG, Hoi Leong Lee, Haodong Liu

Biomedical regression tasks require predicting continuous targets from heterogeneous and unstructured evidence. While Large Language Models (LLMs) provide a robust interface for reasoning over mixed modalities, they are inherently limited by their discrete tokenization and cross-entropy objectives, which lack awareness of numerical proximity. To bridge this gap, we present \textbf{SPR-RAFT}, a parameter-efficient and regression-aware framework that adapts frozen LLMs for high-precision regression. SPR-RAFT introduces a dual-module architecture: a learnable soft prompt that conditions the LLM to route numerical reasoning into a specific latent state, and a lightweight \texttt{[REG]}-anchored head for numerical reasoning consolidation. Crucially, we align these two modalities via a hybrid objective that combines distribution-based text generation with representation-based robust regression. This ensures the model remains both semantically coherent and numerically calibrated. With only $\sim$0.04\% trainable parameters, SPR-RAFT consistently outperforms prompting strategies, standard fine-tuning, and non-LLM baselines across diverse biomedical benchmarks, including clinical trial duration, biological age estimation, and molecular property prediction.

Applications · Health / Medicine

Hao Zhou, Simon Lee, Cyrus Tanade, Keum San Chun, Juhyeon Lee, Migyeong Gwak, Megha Thukral, Justin Sung, Eugene Hwang, Mehrab Bin Morshed 等

Biosignals acquired from different locations on the body often provide temporally ordered views of the same underlying physiological process. However, most existing self-supervised learning methods treat these signals as interchangeable views, overlooking the directional temporal dynamics that link them. A canonical example is the relationship between electrocardiography (ECG), which captures the electrical activation initiating each heartbeat, and photoplethysmography (PPG), which records the resulting peripheral pulse delayed by vascular dynamics. To capture this structured relationship, we introduce xMAE, a biosignal pretraining framework that leverages masked cross-modal reconstruction across temporally ordered biosignals as a training-time constraint to encourage physiologically meaningful timing structure in the learned representations. We show that pretraining with xMAE yields representations that outperform both unimodal and multimodal baselines on 15 of 19 downstream tasks, including cardiovascular outcome prediction, abnormal laboratory test detection, sleep staging, and demographic inference, while generalizing across devices, body locations, and acquisition settings. Further analysis suggests that the ECG--PPG timing structure is reflected in the learned PPG representations. More broadly, xMAE demonstrates the effectiveness of incorporating temporal structure into multimodal pretraining when signals observe different stages of a shared underlying process.

Applications · Health / Medicine

Maria Elkjær Montgomery, Christian Igel, Mikkel Odgaard, Martin Sillesen, Mads Nielsen

How do we map numeric values to representations in transformer-based sequence processing, particularly in electronic health record (EHR) data? We systematically compare discrete, continuous, and hybrid value embeddings using synthetic arithmetic tasks embedded within real-world EHR data, as well as real-world clinical prediction tasks. Our study reveals trade-offs between numeric precision, optimisation stability, and architectural flexibility. We find that representations that explicitly model value-concept interactions perform best on precision-sensitive arithmetic tasks when architectural constraints permit. Hybrid token-based approaches that retain numeric values but apply binning prior to projection provide a more robust and broadly applicable alternative, with the optimal number of bins following a simple empirically derived power-law in dataset size. Across tasks, models consistently exhibit reliable “good enough” numeric computation rather than exact arithmetic, while clinical gains from incorporating laboratory values are task-dependent. This suggests that robustness and deployability often outweigh maximal numeric precision in practice, motivating hybrid token-based approaches as a practical default.

Applications · Health / Medicine

Xiaoling Luo, Shuo Yang, Qihao Xu, Chengliang Liu, Jiansong Zhang, Zhuoqin Yang, Zhihui Lai, Linlin Shen

Existing deep learning models have demonstrated potential in Diabetic retinopathy (DR) diagnosis, but they still suffer from three key challenges: reliance on single-source inputs, opaque and untraceable reasoning processes, and the absence of a mechanism for result verification. Thus, we propose a provenance-enabled concept-based framework for multi-view DR diagnostic (ProConMV), which integrates DR lesion masks, clinical text and multi-view data, utilizing multimodal prompt analysis and visual-text concept interaction to learn the interpretable multi-source input. During the reasoning stage, the proposed framework introduces lesion concepts for causal reasoning chains combining clinical guidelines, and adds doctor intervention for human-machine collaboration. For dynamic fusion decision and verification in multi-view DR diagnosis, we derive via generalization theory that incorporating each view’s lesion concept uncertainty and grading uncertainty reduces the generalization error upper bound. Accordingly, we design a dual uncertainty-aware module to enable provenance-based verification, ultimately enabling verifiable analysis of DR diagnostic results. Extensive experiments conducted on two public multi-view DR datasets demonstrate the effectiveness of our method.

Applications · Health / Medicine

Hiroki Yanagisawa, Shunta Akiyama

Interval-censored data present unique challenges in statistical analysis due to the partial observability of event times within known intervals, requiring assumptions about the censoring mechanism. This paper explores the theoretical relationship between two foundational assumptions: independent monitoring and non-informative censoring. We demonstrate that these assumptions are equivalent for Case-1 interval-censored data, but not for Case-$K$ interval-censored data, where $K \geq 2$, through a synthetic dataset example. Additionally, we propose the first strictly proper scoring rule and calibration metric specifically designed for interval-censored data under the constant-sum assumption and the non-informative censoring assumption, respectively. Our empirical evaluations on real-world datasets show that a neural network model trained with our scoring rule is competitive with established statistical baselines, offering enhanced flexibility. These contributions provide significant advancements in the theoretical understanding and practical analysis of interval-censored data.

Applications · Health / Medicine

Guanghui Min, Tianhao Huang, Ke Wan, Qi Wang, Chen Chen

Reliable epidemic forecasting is critical for public health decision-making yet remains challenging due to data sparsity and the non-stationary nature of disease dynamics. While recent hybrid models attempt to integrate mechanistic principles with data-driven approaches, they often relegate mechanistic priors to merely auxiliary features or regularization terms. This design not only obscures the interpretability of the mechanistic contribution but also fails to inherit the capability of physical models to generalize under non-stationary dynamics, as the core architecture remains predominantly data-driven. To address these limitations, we propose EpiDiff, a unified framework that synergizes epidemiological domain knowledge with the generative power of diffusion models. Unlike methods that rigidly fuse features, EpiDiff employs a novel uncertainty-aware steering mechanism during inference. Specifically, we quantify the posterior uncertainty of mechanistic estimations and use it to dynamically modulate the diffusion process. Extensive experiments on real-world datasets demonstrate that EpiDiff consistently outperforms state-of-the-art baselines in accuracy and robustness, particularly under non-stationary distributions, while offering transparent insights into model reliance by explicitly visualizing when the forecast is governed by mechanistic laws versus data-driven patterns. Our code and datasets are available at https://anonymous.4open.science/r/epidiff-4782.

Applications · Health / Medicine

Zekuan Shang, Xiaosong Han, Liupu Wang, Wei Du, Peng Zhao, Yuanshu Li, Yubin Xiao, Xuan Wu, You Zhou

For denoising Spatially Resolved Transcriptomics (SRT) data, existing methods often construct spot and gene graphs to model inter-spot and inter-gene relationships, respectively. However, these methods often introduce spurious similarity biases among spots when constructing the spot graph and fail to capture nonlinear relationships among genes when constructing the gene graph. Moreover, ineffective graph fusion strategies further bottleneck denoising performance. To address these challenges, we propose SpaEF, which innovatively constructs spot and gene graphs with two Large Models (LMs) to inject prior knowledge for mitigating biases and capture nonlinear relationships, and then fuses them with the proposed element-wise graph autoencoder. As far as we know, SpaEF is the first SRT denoising method that utilizes pre-trained LMs to construct spot and gene graphs. Experiments on four real-world datasets with corresponding downstream tasks demonstrate that SpaEF not only outperforms SOTA denoising methods in accuracy but also exhibits strong robustness across tasks.

Applications · Health / Medicine

Evgeny S. Saveliev, Samuel Holt, Nabeel Seedat, David Bentley, Jim Weatherall, Mihaela van der Schaar

Large Language Models (LLMs) offer a promising avenue for scientific discovery, yet their application to symbolic regression is often constrained by inefficient search strategies and coarse feedback signals. Current methods typically guide LLMs using scalar metrics (e.g., global Mean Squared Error), which fail to identify which specific components of a proposed equation are driving performance or causing error. We introduce \textit{Influence-Guided Symbolic Regression} (IGSR), a method that frames equation discovery as an iterative two-step process combining diverse term generation with rigorous selection: an LLM generates candidate basis functions $\psi_j(\mathbf{x})$ for a linear model, which are then evaluated using granular influence scores $\Delta_j$. These scores quantify each term's marginal contribution to generalization accuracy, enabling an influence-guided pruning process that systematically refines the model structure. Integrating this mechanism into a Monte Carlo Tree Search (MCTS) enables navigating the combinatorial search space while balancing exploration of novel functional forms with exploitation of high-influence components. We demonstrate IGSR's effectiveness across a diverse suite of benchmarks, including LLM-SRBench, pharmacological PKPD models, an epidemiological simulation, and real-world genomic data. Notably, we validate the framework's capacity for genuine discovery in a case study using a high-dimensional biological dataset, in which IGSR identified a novel relationship between DNA methylation and RNA Polymerase II pausing; a hypothesis that was subsequently supported via wet-lab experimentation.

Applications · Health / Medicine

Zongzhe Xu, Zitao Shuai, Eideen Mozaffari, Ravi Aysola, Rajesh Kumar, Yuzhe Yang

We present SleepLM, a family of sleep-language foundation models that enable human sleep alignment, interpretation, and interaction with natural language. Despite the critical role of sleep, learning-based sleep analysis systems operate in closed label spaces (e.g., predefined stages or events) and fail to describe, query, or generalize to novel sleep phenomena. SleepLM bridges natural language and multimodal polysomnography, enabling language-grounded representations of sleep physiology. To support this alignment, we introduce a multilevel sleep caption generation pipeline that enables the curation of the first large-scale sleep-text dataset, comprising over 100K hours of data from more than 10,000 individuals. Furthermore, we present a unified pretraining objective that combines contrastive alignment, caption generation, and signal reconstruction to better capture physiological fidelity and cross-modal interactions. Extensive experiments on real-world sleep understanding tasks verify that SleepLM outperforms state-of-the-art in zero-shot and few-shot learning, cross-modal retrieval, and sleep captioning. Importantly, SleepLM also exhibits intriguing capabilities including language-guided event localization, targeted insight generation, and zero-shot generalization to unseen tasks. All code and data will be open-sourced.

Applications · Health / Medicine

Luru Jing, Cong Cong, Yanyuan Chen, Yongzhi Cao

Federated learning (FL) offers a promising framework for collaborative digital pathology by enabling model training across institutions. However, real-world deployments face heterogeneity arising from diverse multiple instance learning (MIL) architectures and heterogeneous feature extractors across institutions. We propose FedHD, a novel FL framework that performs local Gaussian-mixture feature alignment tailored for WSI analysis. Instead of exchanging model parameters, each client independently distills semantically rich synthetic feature representations aligned with the distribution of real WSIs. To preserve diagnostic diversity, FedHD adopts a one-to-one distillation strategy, generating a synthetic counterpart for each real slide to avoid over-compression. During federation, a curriculum-based integration strategy progressively incorporates cross-site synthetic features into local training once performance plateaus. Furthermore, an optional interpretation module reconstructs pseudo-patches from synthetic embeddings, enhancing transparency. FedHD is architecture-agnostic, privacy-preserving, and supports personalized yet collaborative training across diverse institutions. Experiments on TCGA-IDH, CAMELYON16, and CAMELYON17 show that FedHD consistently outperforms state-of-the-art federated and distillation baselines.

Applications · Health / Medicine

Itai Zilberstein, Ioannis Anagnostides, Zachary Sollie, Arman Kilic, Tuomas Sandholm

Online matching has been a mainstay in domains such as Internet advertising and organ allocation, but practical algorithms often lack strong theoretical guarantees. We take an important step toward addressing this by developing new online matching algorithms based on a coarsening approach. Although coarsening typically implies a loss of granularity, we show that, to the contrary, aggregating offline nodes into capacitated clusters can yield near-optimal theoretical guarantees. We apply our methodology to heart transplant allocation to develop theoretically grounded policies based on structural properties of historical data. Furthermore, in simulations based on real data, our policy closely matches the performance of the omniscient benchmark, achieving competitive ratio 0.91, drastically higher than the US status quo policy's 0.51. Our work bridges the gap between data-driven heuristics and pessimistic theoretical lower bounds.

Applications · Health / Medicine

Jiafa Ruan, Zongxin Yang, Ruijie Quan, Liyang Xu, Yi Yang

Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics. In practice, perturbation responses are rarely gene-independent but instead manifest as coordinated, program-level transcriptional changes among functionally related genes. However, most existing methods do not explicitly model such coordination, due to gene-wise modeling paradigms and reliance on static biological priors that cannot capture dynamic program reorganization. To address these limitations, we propose scBIG, a module-inductive perturbation prediction framework that explicitly models coordinated gene programs. scBIG induces coherent gene programs from data via Gene-Relation Clustering, captures inter-program interactions through a Gene-Cluster-Aware Encoder, and preserves modular coordination using structure-aware alignment objectives. These structured representations are then modeled using conditional flow matching to enable flexible and generalizable perturbation prediction. Extensive experiments on multiple single-cell perturbation benchmarks show that scBIG consistently outperforms state-of-the-art methods, particularly on unseen and combinatorial perturbation settings, achieving an average improvement of 6.7% over the strongest baselines.

Applications · Health / Medicine

Ruihan Guo, Chaoran Cheng, Zhanghan Ni, Neil He, Bangji Yang, Ge Liu

Predicting protein mutation effects is fundamental to protein engineering and disease variant interpretation, yet experimental mutation data remain accurate but extremely sparse. Large-scale computational augmentation offers scalability, but introduces heterogeneous and poorly calibrated supervision signals arising from distinct modeling paradigms. We construct a PDB-wide, structure-aligned mutation augmentation dataset that exhaustively enumerates single-site substitutions and aligns mutation signals from physics-based energy models, protein language models, and structure-conditioned inverse folding models. Large-scale analysis under a unified mutation preference representation reveals substantial differences in preference structure, confidence, and cross-model agreement, indicating that disagreement is pervasive and reflects conflicting inductive biases rather than random noise. Motivated by these observations, we propose an unsupervised multi-source mutation preference distillation framework that learns from relative mutation preferences while explicitly modeling cross-source disagreement. Without using any experimental mutation labels during training, our approach achieves consistent improvements on the ProteinGym benchmark over zero-shot baselines and naive multi-source fusion strategies. We release the dataset and evaluation pipeline to support reproducible studies of protein mutation effects.

Applications · Health / Medicine

Hengyuan Cao, Shizhuo Cheng, Mingxuan Liu, Weicheng Huang, Yunhong Lu, chenxi cai, Yan Zhang, Min Zhang

The rapid evolution of generative models has unlocked new potentials in protein binder design, a pivotal task in structural biology, by facilitating end-to-end generation via joint sequence-structure modeling or hallucination. However, existing approaches are predominantly implemented under a single-target, single-state assumption, limiting their ability to model multi-target or multi-state interactions required for advanced function-oriented protein design. Here, we introduce Chamaileon, which unifies multi-target and multi-state binder design by formulating the problem as cross-context binding landscape modeling. The framework is underpinned by a training paradigm termed \textit{In-Context Complex Co-Design (I3CD)} for context-aware sequence-structure co-modeling. During inference, we employ \textit{Mixture-of-Paths Sampling (MoPS)}, a scalable strategy that optimizes a single sequence across contexts while alleviating the scarcity of high-quality multi-conformational paired data. Extensive evaluation on our newly constructed benchmark, \textit{CROSS}, demonstrates that Chamaileon effectively generates sequences adaptable to diverse conformational landscapes and multi-target requirements.