Guan Yongtao, Levy Daniel
bioRxiv. 2025 May 29:2025.01.16.633369. doi: 10.1101/2025.01.16.633369.
We present a novel knockoff construction method, and demonstrate its superior performance in two applications: identifying proteomic signatures of age and genetic fine mapping. Both applications involve datasets of highly correlated features, but they differ in the abundance of driver associations. Our primary contribution is the invention of the reflection knockoff, which is constructed from mirror images - obtained via Householder reflection - of the original features. The reflection knockoffs substantially outperform Model-X knockoffs in feature selection, particularly when features are highly correlated. Our secondary contribution is a simple method to aggregate multiple sets of identically distributed knockoff statistics to improve the consistency of knockoff filters. In the study of proteomic signatures of age, single feature tests showed overly abundant proteomic association with age. Knockoff filters using reflection knockoffs and aggregation, however, revealed that a majority of these associations are hitchhikers instead of drivers. When applied to genetic fine mapping, knockoff filters using reflection knockoffs and aggregation outperform a state-of-the-art method. We discuss a potentially exciting application of reflection knockoffs: sharing genetic data without raising concerns about privacy and regulatory violations.
我们提出了一种新颖的替代构建方法，并在两个应用中展示了其卓越性能：识别年龄的蛋白质组学特征以及基因精细定位。这两个应用都涉及高度相关特征的数据集，但驱动关联的丰富程度有所不同。我们的主要贡献是发明了反射替代，它是由原始特征通过豪斯霍尔德反射获得的镜像构建而成。在特征选择方面，反射替代显著优于X模型替代，特别是当特征高度相关时。我们的次要贡献是一种简单的方法，用于聚合多组同分布的替代统计量，以提高替代筛选器的一致性。在年龄的蛋白质组学特征研究中，单特征测试显示与年龄的蛋白质组关联过多。然而，使用反射替代和聚合的替代筛选器表明，这些关联中的大多数是搭便车者而非驱动因素。当应用于基因精细定位时，使用反射替代和聚合的替代筛选器优于一种先进方法。我们讨论了反射替代一个潜在的令人兴奋的应用：在不引发隐私和监管违规担忧的情况下共享基因数据。
