用遗传算法筛选癌症多组学特征,提升生存预测精度与模型简洁性
Genetic algorithms for multi-omic feature selection: a comparative study in cancer survival analysis

- 分层优化+跨层交互,逐步筛选跨模态互补生物标志物
- 在三个TCGA队列上显著改善准确率与模型复杂度平衡
- 适合需要高精度生存预测的肿瘤组学研究者
多组学数据为癌症生物标志物发现提供了机遇,但其高维性和小样本特性使构建精简高效的标志物组合面临挑战。本文提出Sweeping*,一种多视图、多目标的遗传算法框架,通过交替执行单视图与多视图优化,先在各组学层内识别关键特征,再联合评估跨层交互作用,迭代引导下一轮单视图搜索。采用NSGA3-CHS作为子优化器,结合生存预测任务,以协和指数(concordance index)和根瘦度(root-leanness)共同优化预测性能与特征集大小。在三个TCGA队列上测试五种Sweeping*策略,通过5折交叉验证评估超体积与帕累托差值(Pareto delta),结果表明:当存在足够生存信号时,Sweeping*能有效提升准确率与复杂度权衡;整合多组学信息可超越仅临床变量模型,但增益具有队列依赖性。
原文摘要 · Abstract (English)
Multi-omic datasets offer opportunities for improved biomarker discovery in cancer research, but their high dimensionality and limited sample sizes make identifying compact and effective biomarker panels challenging. Feature selection in large-scale omics can be efficiently addressed by combining machine learning with genetic algorithms, which naturally support multi-objective optimization of predictive accuracy and biomarker set size. However, genetic algorithms remain relatively underexplored for multi-omic feature selection, where most approaches concatenate all layers into a single feature space. To address this limitation, we introduce Sweeping*, a multi-view, multi-objective algorithm alternating between single- and multi-view optimization. It employs a nested single-view multi-objective optimizer, and for this study we use the genetic algorithm NSGA3-CHS. It first identifies informative biomarkers within each layer, then jointly evaluates cross-layer interactions; these multi-omic solutions guide the next single-view search. Through repeated sweeps, the algorithm progressively identifies compact biomarker panels capturing cross-modal complementary signals. We benchmark five Sweeping* strategies, including hierarchical and concatenation-based variants, using survival prediction on three TCGA cohorts. Each strategy jointly optimizes predictive accuracy and set size, measured via the concordance index and root-leanness. Overall performance and estimation error are assessed through cross hypervolume and Pareto delta under 5-fold cross-validation. Our results show that Sweeping* can improve the accuracy-complexity trade-off when sufficient survival signal is present and that integrating omic layers can enhance survival prediction beyond clinical-only models, although benefits remain cohort-dependent.
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