arXiv:2606.06196cs.LG2026-06中稿 · publication in the…被引 1

用机器学习发现亨廷顿病自然进展阶段,避免人为划分偏差。

A Machine Learning-Based Framework for Discovering Huntington's Disease Stages: Integrating Graph Representation Learning and clustering to Uncover Progression Dynamics in Longitudinal Enroll-HD Dataset

  • 基于动态图表示学习捕捉患者间纵向数据的时序关系
  • 在302人、1477次随访数据中识别出4个稳定且区分明显的疾病阶段
  • 适合研究神经退行性疾病进展或开发个性化诊疗方案的学者

亨廷顿病是一种逐渐加重的脑部疾病,影响运动、认知和行为。准确一致地识别疾病阶段对理解病程、患者分组、个性化治疗及新药研发至关重要。现有临床分期依赖预设阈值和专家判断,易受评分者差异影响,且难以反映阶段内变异。为此,我们提出一种基于动态图表示学习的无监督机器学习框架,从纵向临床数据中捕捉患者间的时间关联。利用学习到的表征,采用K-means++聚类并迭代增加聚类数(k),通过稳定性分析验证结果稳健性,揭示超越初始最优解的有意义分组。该方法应用于Enroll-HD队列中的302名个体(共1,477次随访,每次44项临床指标,80%为显性期患者),在四维潜在空间中实现稳健聚类,识别出四个统计上显著且临床特征分明的疾病阶段。各阶段对应明确的临床测量边界,重叠度低于传统分期方法。

原文摘要 · Abstract (English)

Huntington's disease (HD) is a progressive brain disorder that gradually affects movement, cognitive function, and behavior. Identifying the stage of the disease accurately and consistently is important for understanding its course, grouping patients, personalized care, and discovering treatment. Existing clinical staging frameworks rely primarily on predefined clinical measurement thresholds and clinical expert decisions, yet these discrete cut-offs may obscure meaningful intra-stage variability and remain vulnerable to inter-rater differences, especially in motor and functional assessments. To address these limitations, we developed an unsupervised machine learning framework based on dynamic graph representation learning to capture temporal relationships within and across patients from longitudinal clinical measurements. Using the learned representations, we applied K-means++ clustering to identify well-separated groups. We then iteratively increased the number of clusters (k), using stability analysis to assess robustness and reveal additional meaningful clusters beyond the initial optimal solution. We applied the framework to 302 individuals from the Enroll-HD cohort (1,477 visits, 44 clinical variables per visit; 80% manifest participants), enabling data-driven discovery of HD stages reflecting natural clinical progression. Despite the limited cohort size, the proposed framework achieved robust clustering performance using a four-dimensional latent space, identifying four meaningful and statistically distinct disease stages through clustering stability analysis. Each stage corresponded to well-defined clinical measurement boundaries, with minimal overlap compared to previously established clinical staging methods.

神经退行性疾病聚类分析动态图学习

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