用可解释AI无监督识别跨癌种的生存风险分组,结果可解读且效果显著。
Unsupervised risk factor identification across cancer types and data modalities via explainable artificial intelligence
- 直接优化生存异质性,不依赖代理指标,适用于任意数据模态和模型。
- 在多发性骨髓瘤和非小细胞肺癌中均发现生存差异显著的患者亚群。
- 结果可解释,特征与已知风险因子高度一致,适合临床决策支持。
风险分层是临床决策的关键工具,但现有方法常无法将复杂的生存分析转化为可操作的临床标准。本文提出一种新型无监督机器学习方法,通过可微分的多变量对数秩统计量直接优化患者分组的生存异质性。不同于依赖代理指标的主流方法,该方法可训练任意神经网络架构,适配任意数据模态,以识别具有预后差异的患者群体。我们在模拟实验中全面评估该方法,并在实践中应用于两种不同癌症:基于多发性骨髓瘤患者的实验室参数,以及非小细胞肺癌患者的计算机断层扫描图像,均成功识别出生存结局显著不同的患者亚群。事后可解释性分析揭示了决定分组的关键临床特征,与已有风险因素高度吻合,有力证明了方法的有效性。该泛癌、模型无关的方法为临床风险分层提供了重要进展,可在多种数据类型中发现新预后标志物,并提供可解释结果,有望助力肿瘤学及其他领域的治疗个性化与临床决策。
原文摘要 · Abstract (English)
Risk stratification is a key tool in clinical decision-making, yet current approaches often fail to translate sophisticated survival analysis into actionable clinical criteria. We present a novel method for unsupervised machine learning that directly optimizes for survival heterogeneity across patient clusters through a differentiable adaptation of the multivariate logrank statistic. Unlike most existing methods that rely on proxy metrics, our approach represents novel methodology for training any neural network architecture on any data modality to identify prognostically distinct patient groups. We thoroughly evaluate the method in simulation experiments and demonstrate its utility in practice by applying it to two distinct cancer types: analyzing laboratory parameters from multiple myeloma patients and computed tomography images from non-small cell lung cancer patients, identifying prognostically distinct patient subgroups with significantly different survival outcomes in both cases. Post-hoc explainability analyses uncover clinically meaningful features determining the group assignments which align well with established risk factors and thus lend strong weight to the methods utility. This pan-cancer, model-agnostic approach represents a valuable advancement in clinical risk stratification, enabling the discovery of novel prognostic signatures across diverse data types while providing interpretable results that promise to complement treatment personalization and clinical decision-making in oncology and beyond.
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