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Register a new userOptimal False Discovery Rate Control for Large Scale Multiple Testing with Auxiliary Information
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Added by
Hongyuan Cao Prof
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
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Large-scale multiple testing is a fundamental problem in high dimensional statistical inference. It is increasingly common that various types of auxiliary information, reflecting the structural relationship among the hypotheses, are available. Exploiting such auxiliary information can boost statistical power. To this end, we propose a framework based on a two-group mixture model with varying probabilities of being null for different hypotheses a priori, where a shape-constrained relationship is imposed between the auxiliary information and the prior probabilities of being null. An optimal rejection rule is designed to maximize the expected number of true positives when average false discovery rate is controlled. Focusing on the ordered structure, we develop a robust EM algorithm to estimate the prior probabilities of being null and the distribution of $p$-values under the alternative hypothesis simultaneously. We show that the proposed method has better power than state-of-the-art competitors while controlling the false discovery rate, both empirically and theoretically. Extensive simulations demonstrate the advantage of the proposed method. Datasets from genome-wide association studies are used to illustrate the new methodology.
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Transfer learning for high-dimensional Gaussian graphical models (GGMs) is studied with the goal of estimating the target GGM by utilizing the data from similar and related auxiliary studies. The similarity between the target graph and each auxiliary graph is characterized by the sparsity of a divergence matrix. An estimation algorithm, Trans-CLIME, is proposed and shown to attain a faster convergence rate than the minimax rate in the single study setting. Furthermore, a debiased Trans-CLIME estimator is introduced and shown to be element-wise asymptotically normal. It is used to construct a multiple testing procedure for edge detection with false discovery rate control. The proposed estimation and multiple testing procedures demonstrate superior numerical performance in simulations and are applied to infer the gene networks in a target brain tissue by leveraging the gene expressions from multiple other brain tissues. A significant decrease in prediction errors and a significant increase in power for link detection are observed.
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Adaptive multiple testing with covariates is an important research direction that has gained major attention in recent years. It has been widely recognized that leveraging side information provided by auxiliary covariates can improve the power of false discovery rate (FDR) procedures. Currently, most such procedures are devised with $p$-values as their main statistics. However, for two-sided hypotheses, the usual data processing step that transforms the primary statistics, known as $z$-values, into $p$-values not only leads to a loss of information carried by the main statistics, but can also undermine the ability of the covariates to assist with the FDR inference. We develop a $z$-value based covariate-adaptive (ZAP) methodology that operates on the intact structural information encoded jointly by the $z$-values and covariates. It seeks to emulate the oracle $z$-value procedure via a working model, and its rejection regions significantly depart from those of the $p$-value adaptive testing approaches. The key strength of ZAP is that the FDR control is guaranteed with minimal assumptions, even when the working model is misspecified. We demonstrate the state-of-the-art performance of ZAP using both simulated and real data, which shows that the efficiency gain can be substantial in comparison with $p$-value based methods. Our methodology is implemented in the $texttt{R}$ package $texttt{zap}$.
Variable selection on the large-scale networks has been extensively studied in the literature. While most of the existing methods are limited to the local functionals especially the graph edges, this paper focuses on selecting the discrete hub structures of the networks. Specifically, we propose an inferential method, called StarTrek filter, to select the hub nodes with degrees larger than a certain thresholding level in the high dimensional graphical models and control the false discovery rate (FDR). Discovering hub nodes in the networks is challenging: there is no straightforward statistic for testing the degree of a node due to the combinatorial structures; complicated dependence in the multiple testing problem is hard to characterize and control. In methodology, the StarTrek filter overcomes this by constructing p-values based on the maximum test statistics via the Gaussian multiplier bootstrap. In theory, we show that the StarTrek filter can control the FDR by providing accurate bounds on the approximation errors of the quantile estimation and addressing the dependence structures among the maximal statistics. To this end, we establish novel Cramer-type comparison bounds for the high dimensional Gaussian random vectors. Comparing to the Gaussian comparison bound via the Kolmogorov distance established by citet{chernozhukov2014anti}, our Cramer-type comparison bounds establish the relative difference between the distribution functions of two high dimensional Gaussian random vectors. We illustrate the validity of the StarTrek filter in a series of numerical experiments and apply it to the genotype-tissue expression dataset to discover central regulator genes.
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