arXiv:2602.21648cs.LGq-bio.QM2026-02

整合多模态数据预测乳腺癌5年生存率,兼顾模型准确与公平性。

Multimodal Survival Modeling and Fairness-Aware Clinical Machine Learning for 5-Year Breast Cancer Risk Prediction

  • 融合临床、基因和拷贝数变异数据,用弹性网与梯度提升树建模。
  • 模型在测试集上达到96.6的AUC和80.4的平均精度,表现优异。
  • 重点评估年龄、分型等亚组公平性,适合医疗决策支持场景。

临床风险预测模型在真实世界中常因校准不佳、可迁移性差及亚组差异而表现欠佳。这些挑战在高维多模态癌症数据中尤为突出,其特征交互复杂且呈现p >> n结构。本文提出一个完全可复现的多模态机器学习框架,用于乳腺癌5年总生存率预测,整合了来自METABRIC队列的临床变量与高维转录组及拷贝数变异(CNA)特征。经方差与稀疏性筛选及降维处理后,采用分层训练/验证/测试划分,并基于验证集调优超参数。对比两种生存模型:弹性网正则化Cox模型(CoxNet)与基于XGBoost的梯度提升生存树。CoxNet具备嵌入式特征选择与稳定估计能力,而XGBoost能捕捉非线性效应与高阶交互。性能评估使用时间依赖的ROC曲线下面积(AUC)、平均精度(AP)、校准曲线、Brier评分及自举95%置信区间。CoxNet在验证集与测试集上的AUC分别为98.3与96.6,AP值为90.1与80.4;XGBoost在验证集与测试集上的AUC为98.6与92.5,AP值为92.5与79.9。公平性诊断显示,模型在不同年龄组、雌激素受体状态、分子亚型及绝经状态间均保持稳定区分能力。本研究构建了一个以治理为导向的多模态生存分析框架,强调校准性、公平性审计、鲁棒性与可复现性,适用于高维临床机器学习。

原文摘要 · Abstract (English)

Clinical risk prediction models often underperform in real-world settings due to poor calibration, limited transportability, and subgroup disparities. These challenges are amplified in high-dimensional multimodal cancer datasets characterized by complex feature interactions and a p >> n structure. We present a fully reproducible multimodal machine learning framework for 5-year overall survival prediction in breast cancer, integrating clinical variables with high-dimensional transcriptomic and copy-number alteration (CNA) features from the METABRIC cohort. After variance- and sparsity-based filtering and dimensionality reduction, models were trained using stratified train/validation/test splits with validation-based hyperparameter tuning. Two survival approaches were compared: an elastic-net regularized Cox model (CoxNet) and a gradient-boosted survival tree model implemented using XGBoost. CoxNet provides embedded feature selection and stable estimation, whereas XGBoost captures nonlinear effects and higher-order interactions. Performance was assessed using time-dependent area under the ROC curve (AUC), average precision (AP), calibration curves, Brier score, and bootstrapped 95 percent confidence intervals. CoxNet achieved validation and test AUCs of 98.3 and 96.6, with AP values of 90.1 and 80.4. XGBoost achieved validation and test AUCs of 98.6 and 92.5, with AP values of 92.5 and 79.9. Fairness diagnostics showed stable discrimination across age groups, estrogen receptor status, molecular subtypes, and menopausal state. This work introduces a governance-oriented multimodal survival framework emphasizing calibration, fairness auditing, robustness, and reproducibility for high-dimensional clinical machine learning.

生存分析乳腺癌公平性多模态

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