ROOFS工具可自动选出最适合生物标志物筛选的特征选择方法。
ROOFS: RObust biOmarker Feature Selection
- 通过综合评估多种方法,自动推荐最优特征选择策略。
- 在肺癌免疫治疗数据上验证,优于常用LASSO方法。
- 适合临床研究者快速选型,提升模型可重复性。
特征选择(FS)对生物标志物发现和临床预测建模至关重要。尽管过去几十年相关方法发展成熟,但其在实际生物医学研究中的应用仍不充分。生物医学数据常面临高维、小样本、多重共线性和缺失值等挑战,使特征选择复杂化。为此,我们提出ROOFS(RObust biOmarker Feature Selection),一个可在https://gitlab.inria.fr/compo/roofs获取的Python工具包,帮助研究者根据自身问题选择合适的特征选择方法。ROOFS在用户数据上基准测试多个方法,并生成报告,涵盖下游预测性能(使用乐观校正估计)、稳定性、单个特征的鲁棒性,以及在半合成数据上的真阳性率与假阳性率。我们在针对肺癌抗PD-(L)1免疫治疗耐药性的PIONeeR临床试验数据上验证了ROOFS的有效性。在包含34种特征选择方法中,我们评估了23种与11种分类器组合(共253个模型),发现基于t检验和逻辑回归的贝叶斯-霍希伯格错误发现率调整p值并集的过滤方法表现最佳,优于包括广泛使用的LASSO在内的其他方法。结论:通过全面基准测试,ROOFS有潜力提升特征选择发现的可重复性,并增强临床模型的转化价值。
原文摘要 · Abstract (English)
Feature selection (FS) is essential for biomarker discovery and clinical predictive modeling. Over the past decades, methodological literature on FS has become rich and mature, offering a wide spectrum of algorithmic approaches. However, much of this methodological progress has not fully translated into applied biomedical research. Moreover, challenges inherent in biomedical data, such as high-dimensional feature space, low sample size, multicollinearity, and missing values, make FS non-trivial. To help bridge this gap between methodological development and practical application, we propose ROOFS (RObust biOmarker Feature Selection), a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. ROOFS benchmarks multiple FS methods on the user's data and generates reports summarizing a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, robustness of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of ROOFS on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. Of the 34 FS methods gathered in ROOFS, we evaluated 23 in combination with 11 classifiers (253 models) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including widely used LASSO. We conclude that comprehensive benchmarking with ROOFS has the potential to improve the reproducibility of FS discoveries and increase the translational value of clinical models.
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