用非对称Shapley值更准确衡量基因在临床预测中的重要性
How important are the genes to explain the outcome - the asymmetric Shapley value as an honest importance metric for high-dimensional features
- 提出非对称Shapley值解决基因与临床变量共线性问题
- 在结直肠癌无进展生存预测中验证方法有效性
- 适合处理有因果方向的高维生物特征分析
在临床预测中,基因等高维特征的重要性常通过加入传统临床变量后预测性能的变化来评估,但该方法未考虑变量间的共线性及已知依赖方向。本文建议采用非对称Shapley值作为更合适的特征重要性度量,特别适用于疾病状态介导基因效应且存在未知方向混杂因素的场景。我们推导出该设定下局部与全局非对称Shapley值的高效计算算法。局部值有助于统计推断,全局值可将任意预测性能指标分解为各特征的贡献。以结直肠癌患者无进展生存预测为例,完整展示了该框架的应用。
原文摘要 · Abstract (English)
In clinical prediction settings the importance of a high-dimensional feature like genomics is often assessed by evaluating the change in predictive performance when adding it to a set of traditional clinical variables. This approach is questionable, because it does not account for collinearity nor known directionality of dependencies between variables. We suggest to use asymmetric Shapley values as a more suitable alternative to quantify feature importance in the context of a mixed-dimensional prediction model. We focus on a setting that is particularly relevant in clinical prediction: disease state as a mediating variable for genomic effects, with additional confounders for which the direction of effects may be unknown. We derive efficient algorithms to compute local and global asymmetric Shapley values for this setting. The former are shown to be very useful for inference, whereas the latter provide interpretation by decomposing any predictive performance metric into contributions of the features. Throughout, we illustrate our framework by a leading example: the prediction of progression-free survival for colorectal cancer patients.
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