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Zixuan Wen

Publications and source records attributed to Zixuan Wen.

6 recordsLinked to original sources

iLENS: Interpretable LLM-Guided Mixture-of-Experts for Neuroimaging Survival Analysis

Alzheimer's Disease (AD) is a complex neurodegenerative disorder that continues to impact millions of people worldwide. Predicting AD conversion during the prodromal stage remains critical for disease understanding and patient care. As such, survival models are widely used for AD risk prediction, yet they are typically static predictors with limited interpretability and no capacity for natural language reasoning. In this work, we propose iLENS, an interpretable large language model (LLM) guided framework based on mixture-of-experts (MoE) for survival prediction in AD conversion. Our approach uses LLM to synthesize structured neuroimaging measurements and unstructured information to guide expert routing. Our framework demonstrates competitive predictive performance and capability in patient subtyping. Furthermore, our framework provides transparent, biologically grounded rationales for its routing decisions, bridging the gap between high-performance survival analysis and interpretable clinical decision support.

cs.LG

Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts

Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.

cs.LG

Interpretable Alzheimer's Diagnosis via Multimodal Fusion of Regional Brain Experts

Accurate and early diagnosis of Alzheimer's disease (AD) is critical for effective intervention and requires integrating complementary information from multimodal neuroimaging data. However, conventional fusion approaches often rely on simple concatenation of features, which cannot adaptively balance the contributions of biomarkers such as amyloid PET and MRI across brain regions. In this work, we propose MREF-AD, a Multimodal Regional Expert Fusion model for AD diagnosis. It is a Mixture-of-Experts (MoE) framework that models mesoscopic brain regions within each modality as independent experts and employs a gating network to learn subject-specific fusion weights. Utilizing tabular neuroimaging and demographic information from the Alzheimer's Disease Neuroimaging Initiative (ADNI), MREF-AD achieves competitive performance over strong classic and deep baselines while providing interpretable, modality- and region-level insight into how structural and molecular imaging jointly contribute to AD diagnosis. The source code is available at https://github.com/PennShenLab/mref-ad.

cs.LG

Tabular LLMs for Interpretable Few-Shot Alzheimer's Disease Prediction with Multimodal Biomedical Data

Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.

cs.CL

Enabling Few-Shot Alzheimer's Disease Diagnosis on Biomarker Data with Tabular LLMs

Early and accurate diagnosis of Alzheimer's disease (AD), a complex neurodegenerative disorder, requires analysis of heterogeneous biomarkers (e.g., neuroimaging, genetic risk factors, cognitive tests, and cerebrospinal fluid proteins) typically represented in a tabular format. With flexible few-shot reasoning, multimodal integration, and natural-language-based interpretability, large language models (LLMs) offer unprecedented opportunities for prediction with structured biomedical data. We propose a novel framework called TAP-GPT, Tabular Alzheimer's Prediction GPT, that adapts TableGPT2, a multimodal tabular-specialized LLM originally developed for business intelligence tasks, for AD diagnosis using structured biomarker data with small sample sizes. Our approach constructs few-shot tabular prompts using in-context learning examples from structured biomedical data and finetunes TableGPT2 using the parameter-efficient qLoRA adaption for a clinical binary classification task of AD or cognitively normal (CN). The TAP-GPT framework harnesses the powerful tabular understanding ability of TableGPT2 and the encoded prior knowledge of LLMs to outperform more advanced general-purpose LLMs and a tabular foundation model (TFM) developed for prediction tasks. To our knowledge, this is the first application of LLMs to the prediction task using tabular biomarker data, paving the way for future LLM-driven multi-agent frameworks in biomedical informatics.

cs.CL

Knowledge-Driven Feature Selection and Engineering for Genotype Data with Large Language Models

Predicting phenotypes with complex genetic bases based on a small, interpretable set of variant features remains a challenging task. Conventionally, data-driven approaches are utilized for this task, yet the high dimensional nature of genotype data makes the analysis and prediction difficult. Motivated by the extensive knowledge encoded in pre-trained LLMs and their success in processing complex biomedical concepts, we set to examine the ability of LLMs in feature selection and engineering for tabular genotype data, with a novel knowledge-driven framework. We develop FREEFORM, Free-flow Reasoning and Ensembling for Enhanced Feature Output and Robust Modeling, designed with chain-of-thought and ensembling principles, to select and engineer features with the intrinsic knowledge of LLMs. Evaluated on two distinct genotype-phenotype datasets, genetic ancestry and hereditary hearing loss, we find this framework outperforms several data-driven methods, particularly on low-shot regimes. FREEFORM is available as open-source framework at GitHub: https://github.com/PennShenLab/FREEFORM.

cs.LG