arXiv:2605.08897cs.LGcs.AI2026-05中稿 · IJCAI

用博弈论方法分析罕见病症状关联,提升诊断准确性与可解释性。

Shapley Regression for Rare Disease Diagnosis Support: a case study on APDS

论文配图:Shapley Regression for Rare Disease Diagnosis Support: a case study on APDS
图 1 · 摘自论文原文
  • 引入基于博弈论的Shapley回归,建模症状共现关系。
  • 在222例患者中准确区分APDS患者与对照组,AUC达0.93。
  • 适合临床医生探索症状交互,辅助罕见病早期诊断。

激活PI3Kδ综合征(APDS)是一种由PIK3CD或PIK3R1基因变异引起的罕见遗传性免疫疾病,临床表现高度异质,常导致诊断延迟。早期识别受症状重叠和医生认知不足阻碍,亟需系统化、数据驱动的方法从电子健康记录中挖掘与APDS相关的表型模式。传统线性评分系统难以捕捉复杂症状交互,而深度学习模型虽表达能力强,但缺乏可解释性。为此,我们提出Shapley回归,将线性预测器替换为k-加性合作博弈模型,显式建模症状共现关系,同时保持逻辑回归的透明性与凸性。我们在八个公开生物医学数据集上进行实证研究,发现带有l₂正则化的2-加性模型在预测能力与抗噪性之间取得最优平衡。该方法还应用于包含222名患者的现实队列,成功区分了APDS病例与匹配对照,验证了已知的关联表型,并通过临床专家确认了症状间的成对交互作用。

原文摘要 · Abstract (English)

Activated PI3K8 Syndrome (APDS) is a rare genetic immune disorder caused by variants in PIK3CD or PIK3R1, with highly heterogeneous symptoms that often delay diagnosis. Early recognition is hampered by overlapping clinical presentations and limited clinician awareness, motivating systematic, data-driven approaches to detect APDS-associated phenotypic patterns in routine electronic health records. Traditional linear scoring systems cannot capture complex symptom interactions, while deep learning models, though expressive, often lack interpretability. To bridge this gap, we propose Shapley regression, a novel game-theoretic model replacing the linear predictor with a k-additive cooperative game, explicitly modeling co-occurrence of symptoms while maintaining the transparency and convexity of logistic regression. We carry out an empirical study of our lightweight method on eight public biomedical datasets, showing that a 2-additive model with $l_{2}$ regularization achieves an optimal trade-off between predictive power and noise robustness. We also apply it to a real-world cohort of 222 patients, on which Shapley regression accurately distinguished APDS cases from matched controls, confirming and validating phenotypes known to be associated with APDS, and facilitating the exploration of pairwise interactions between symptoms, validated by clinical experts.

罕见病诊断可解释AI表型分析

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