arXiv:2505.15747cs.LGcs.AI2025-05被引 8

用大模型和知识图谱整合碎片化数据,发现阿尔茨海默病新关联。

Multi-modal Integration Analysis of Alzheimer's Disease Using Large Language Models and Knowledge Graphs

  • 不依赖患者ID匹配,通过知识图谱融合多模态数据
  • 发现代谢风险与tau蛋白异常通过神经炎症关联(r>0.6, p<0.001)
  • 适合临床研究者和跨模态分析方向的学者参考

我们提出一种新框架,利用大语言模型(LLMs)和知识图谱整合阿尔茨海默病(AD)研究中的碎片化多模态数据。传统多模态分析需跨数据集匹配患者ID,而本方法实现了在无患者ID匹配前提下,对独立队列中的MRI、基因表达、生物标志物、EEG及临床指标进行群体层面的数据整合。各模态显著特征被作为节点构建知识图谱,大语言模型分析图谱并以自然语言生成潜在关联与假设。研究揭示多个新关系,包括代谢风险因素通过神经炎症影响tau蛋白异常(r>0.6, p<0.001),以及额区EEG通道与特定基因表达谱之间的意外相关性(r=0.42–0.58, p<0.01)。独立数据集交叉验证显示主要发现具有强鲁棒性,各队列效应量一致(方差<15%)。研究结果经专家评审(Cohen's k=0.82)与计算验证支持可复现性。该框架实现概念层跨模态整合,为利用碎片化数据探索AD病理机制及生成可检验假说提供了新路径。

原文摘要 · Abstract (English)

We propose a novel framework for integrating fragmented multi-modal data in Alzheimer's disease (AD) research using large language models (LLMs) and knowledge graphs. While traditional multimodal analysis requires matched patient IDs across datasets, our approach demonstrates population-level integration of MRI, gene expression, biomarkers, EEG, and clinical indicators from independent cohorts. Statistical analysis identified significant features in each modality, which were connected as nodes in a knowledge graph. LLMs then analyzed the graph to extract potential correlations and generate hypotheses in natural language. This approach revealed several novel relationships, including a potential pathway linking metabolic risk factors to tau protein abnormalities via neuroinflammation (r>0.6, p<0.001), and unexpected correlations between frontal EEG channels and specific gene expression profiles (r=0.42-0.58, p<0.01). Cross-validation with independent datasets confirmed the robustness of major findings, with consistent effect sizes across cohorts (variance <15%). The reproducibility of these findings was further supported by expert review (Cohen's k=0.82) and computational validation. Our framework enables cross modal integration at a conceptual level without requiring patient ID matching, offering new possibilities for understanding AD pathology through fragmented data reuse and generating testable hypotheses for future research.

阿尔茨海默病多模态融合大模型知识图谱

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