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arXiv 2406.08784stat.ME
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改进的经验贝叶斯多元多重检验与效应量估计方法

Improved methods for empirical Bayes multivariate multiple testing and effect size estimation

Yunqi Yang, Peter Carbonetto, David Gerard, Matthew Stephens

AI总结:

本文提出改进的经验贝叶斯方法“Ultimate Deconvolution”,通过自适应正则化和协方差估计解析加速,提升多元多重检验中共享模式估计的速度与准确性,并在模拟和49个人体组织eQTL分析中验证了其优越性。

摘要:

估计遗传效应在不同条件下的共享情况对于基因组数据的许多统计分析至关重要。这些数据中产生的共享模式往往具有高度异质性。为了灵活地建模这些异质性共享模式,Urbut等人(2019)提出了多元自适应收缩(MASH)方法,用于联合分析跨多个条件的遗传效应。然而,使用MASH(以及其他多元分析)进行的多元分析需要对共享模式有良好的估计,而高效且准确地估计这些模式仍然具有挑战性。本文描述了新的经验贝叶斯方法,在速度和准确性上均优于现有方法。两个关键思想是:(1)自适应正则化,以提高在条件数量较多的场景下的准确性;(2)通过利用协方差估计的解析结果来提高模型拟合算法的速度。在模拟实验中,我们展示了新方法在模型拟合、样本外表现以及检测真实潜在信号的功效和准确性方面均有提升。在对49个人体组织的eQTL分析中,我们的新分析流程相比现有MASH分析流程取得了更好的模型拟合和更好的样本外表现。我们已将新方法实现为一个R包udr,命名为“Ultimate Deconvolution”,可在GitHub上获取。

英文摘要:

Estimating the sharing of genetic effects across different conditions is important to many statistical analyses of genomic data. The patterns of sharing arising from these data are often highly heterogeneous. To flexibly model these heterogeneous sharing patterns, Urbut et al. (2019) proposed the multivariate adaptive shrinkage (MASH) method to jointly analyze genetic effects across multiple conditions. However, multivariate analyses using MASH (as well as other multivariate analyses) require good estimates of the sharing patterns, and estimating these patterns efficiently and accurately remains challenging. Here we describe new empirical Bayes methods that provide improvements in speed and accuracy over existing methods. The two key ideas are: (1) adaptive regularization to improve accuracy in settings with many conditions; (2) improving the speed of the model fitting algorithms by exploiting analytical results on covariance estimation. In simulations, we show that the new methods provide better model fits, better out-of-sample performance, and improved power and accuracy in detecting the true underlying signals. In an analysis of eQTLs in 49 human tissues, our new analysis pipeline achieves better model fits and better out-of-sample performance than the existing MASH analysis pipeline. We have implemented the new methods, which we call ``Ultimate Deconvolution'', in an R package, udr, available on GitHub.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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