Consider the problem of testing multiple null hypotheses. A classical approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate ($FWER$), the probability of even one false rejection. However, if $s$ is large, control of the $FWER$ is so stringent that the ability of a procedure which controls the $FWER$ to detect false null hypotheses is limited. Consequently, it is desirable to consider other measures of error control. We will consider methods based on control of the false discovery proportion ($FDP$) defined by the number of false rejections divided by the total number of rejections (defined to be 0 if there are no rejections). The false discovery rate proposed by Benjamini and Hochberg (1995) controls $E(FDP)$. Here, we construct methods such that, for any $γ$ and $α$, $P\{FDP>γ\}\le α$. Based on $p$-values of individual tests, we consider stepdown procedures that control the $FDP$, without imposing dependence assumptions on the joint distribution of the $p$-values. A greatly improved version of a method given in Lehmann and Romano \citer10 is derived and generalized to provide a means by which any sequence of nondecreasing constants can be rescaled to ensure control of the $FDP$. We also provide a stepdown procedure that controls the $FDR$ under a dependence assumption.
Sorted L-One Penalized Estimation (SLOPE) has shown the nice theoretical property as well as empirical behavior recently on the false discovery rate (FDR) control of high-dimensional feature selection by adaptively imposing the non-increasing sequence of tuning parameters on the sorted $\ell_1$ penalties. This paper goes beyond the previous concern limited to the FDR control by considering the stepdown-based SLOPE to control the probability of $k$ or more false rejections ($k$-FWER) and the false discovery proportion (FDP). Two new SLOPEs, called $k$-SLOPE and F-SLOPE, are proposed to realize …
Consider the problem of simultaneously testing null hypotheses H_1,...,H_s. The usual approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate (FWER), the probability of even one false rejection. In many applications, particularly if s is large, one might be willing to tolerate more than one false rejection provided the number of such cases is controlled, thereby increasing the ability of the procedure to detect false null hypotheses. This suggests replacing control of the FWER by controlling the probability of k or more fa…
The probability of false discovery proportion (FDP) exceeding $γ\in[0,1)$, defined as $γ$-FDP, has received much attention as a measure of false discoveries in multiple testing. Although this measure has received acceptance due to its relevance under dependency, not much progress has been made yet advancing its theory under such dependency in a nonasymptotic setting, which motivates our research in this article. We provide a larger class of procedures containing the stepup analog of, and hence more powerful than, the stepdown procedure in Lehmann and Romano [Ann. Statist. 33 (2005) 1138-1154] …
A classical approach for dealing with the multiple testing problem is to restrict attention to procedures that control the familywise error rate (FWER), the probability of at least one false rejection. In many applications, one might be willing to tolerate more than one false rejection provided the number of such cases is controlled, thereby increasing the ability of the procedure to detect false null hypotheses. This suggests replacing control of the FWER by controlling the probability of $k$ or more false rejections, which is called the $k$-FWER. In this article, a unified approach is presen…
We study the convergence of the false discovery proportion (FDP) of the Benjamini-Hochberg procedure in the Gaussian equi-correlated model, when the correlation $ρ_m$ converges to zero as the hypothesis number $m$ grows to infinity. By contrast with the standard convergence rate $m^{1/2}$ holding under independence, this study shows that the FDP converges to the false discovery rate (FDR) at rate $\{\min(m,1/ρ_m)\}^{1/2}$ in this equi-correlated model.
We consider the problem of estimating the number of false null hypotheses among a very large number of independently tested hypotheses, focusing on the situation in which the proportion of false null hypotheses is very small. We propose a family of methods for establishing lower $100(1-α)%$ confidence bounds for this proportion, based on the empirical distribution of the $p$-values of the tests. Methods in this family are then compared in terms of ability to consistently estimate the proportion by letting $α\to 0$ as the number of hypothesis tests increases and the proportion decreases. This w…
In a multiple testing problem where one is willing to tolerate a few false rejections, procedure controlling the familywise error rate (FWER) can potentially be improved in terms of its ability to detect false null hypotheses by generalizing it to control the $k$-FWER, the probability of falsely rejecting at least $k$ null hypotheses, for some fixed $k>1$. Simes' test for testing the intersection null hypothesis is generalized to control the $k$-FWER weakly, that is, under the intersection null hypothesis, and Hochberg's stepup procedure for simultaneous testing of the individual null hypothes…
Consider the multiple testing problem of testing null hypotheses $H_1,...,H_s$. A classical approach to dealing with the multiplicity problem is to restrict attention to procedures that control the familywise error rate ($\mathit{FWER}$), the probability of even one false rejection. But if $s$ is large, control of the $\mathit{FWER}$ is so stringent that the ability of a procedure that controls the $\mathit{FWER}$ to detect false null hypotheses is limited. It is therefore desirable to consider other measures of error control. This article considers two generalizations of the $\mathit{FWER}$. …
The false discovery proportion (FDP) is a convenient way to account for false positives when a large number $m$ of tests are performed simultaneously. Romano and Wolf [Ann. Statist. 35 (2007) 1378-1408] have proposed a general principle that builds FDP controlling procedures from $k$-family-wise error rate controlling procedures while incorporating dependencies in an appropriate manner; see Korn et al. [J. Statist. Plann. Inference 124 (2004) 379-398]; Romano and Wolf (2007). However, the theoretical validity of the latter is still largely unknown. This paper provides a careful study of this h…
In a context of multiple hypothesis testing, we provide several new exact calculations related to the false discovery proportion (FDP) of step-up and step-down procedures. For step-up procedures, we show that the number of erroneous rejections conditionally on the rejection number is simply a binomial variable, which leads to explicit computations of the c.d.f., the {$s$-th} moment and the mean of the FDP, the latter corresponding to the false discovery rate (FDR). For step-down procedures, we derive what is to our knowledge the first explicit formula for the FDR valid for any alternative c.d.…
Multiple testing has been a popular topic in statistical research. Although vast works have been done, controlling the false discoveries remains a challenging task when the corresponding test statistics are dependent. Various methods have been proposed to estimate the false discovery proportion (FDP) under arbitrary dependence among the test statistics. One of the main ideas is to reduce arbitrary dependence to weak dependence and then to establish theoretically the strong consistency of the FDP and false discovery rate (FDR) under weak dependence. As a consequence, FDPs share the same asympto…
While traditional multiple testing procedures prohibit adaptive analysis choices made by users, Goeman and Solari (2011) proposed a simultaneous inference framework that allows users such flexibility while preserving high-probability bounds on the false discovery proportion (FDP) of the chosen set. In this paper, we propose a new class of such simultaneous FDP bounds, tailored for nested sequences of rejection sets. While most existing simultaneous FDP bounds are based on closed testing using global null tests based on sorted p-values, we additionally consider the setting where side informatio…
Multiple testing is a fundamental problem in high-dimensional statistical inference. Although many methods have been proposed to control false discoveries, it is still a challenging task when the tests are correlated to each other. To overcome this challenge, various methods have been proposed to estimate the false discovery rate (FDR) and/or the false discovery proportion (FDP) under arbitrary covariance among the test statistics. An interesting finding of these works is that the estimation of FDP and FDR under weak dependence is identical to that under independence. However, Mei et al. (2021…
We consider the class of all multiple testing methods controlling tail probabilities of the false discovery proportion, either for one random set or simultaneously for many such sets. This class encompasses methods controlling familywise error rate, generalized familywise error rate, false discovery exceedance, joint error rate, simultaneous control of all false discovery proportions, and others, as well as seemingly unrelated methods such as gene set testing in genomics and cluster inference methods in neuroimaging. We show that all such methods are either equivalent to a closed testing metho…
Variable selection methods have been developed in linear regression to provide sparse solutions. Recent studies have focused on further interpretations on the sparse solutions in terms of false positive control. In this paper, we consider false negative control for variable selection with the goal to efficiently select a high proportion of relevant predictors. Different from existing studies in power analysis and sure screening, we propose to directly estimate the false negative proportion (FNP) of a decision rule and select the smallest subset of predictors that has the estimated FNP less tha…
Multiple hypothesis testing is a fundamental problem in high dimensional inference, with wide applications in many scientific fields. In genome-wide association studies, tens of thousands of tests are performed simultaneously to find if any SNPs are associated with some traits and those tests are correlated. When test statistics are correlated, false discovery control becomes very challenging under arbitrary dependence. In the current paper, we propose a novel method based on principal factor approximation, which successfully subtracts the common dependence and weakens significantly the correl…
We investigate the performance of a family of multiple comparison procedures for strong control of the False Discovery Rate ($\mathsf{FDR}$). The $\mathsf{FDR}$ is the expected False Discovery Proportion ($\mathsf{FDP}$), that is, the expected fraction of false rejections among all rejected hypotheses. A number of refinements to the original Benjamini-Hochberg procedure [1] have been proposed, to increase power by estimating the proportion of true null hypotheses, either implicitly, leading to one-stage adaptive procedures [4, 7] or explicitly, leading to two-stage adaptive (or plug-in) proced…
This paper extends the theory of false discovery rates (FDR) pioneered by Benjamini and Hochberg [J. Roy. Statist. Soc. Ser. B 57 (1995) 289-300]. We develop a framework in which the False Discovery Proportion (FDP)--the number of false rejections divided by the number of rejections--is treated as a stochastic process. After obtaining the limiting distribution of the process, we demonstrate the validity of a class of procedures for controlling the False Discovery Rate (the expected FDP). We construct a confidence envelope for the whole FDP process. From these envelopes we derive confidence thr…
A popular framework for false discovery control is the random effects model in which the null hypotheses are assumed to be independent. This paper generalizes the random effects model to a conditional dependence model which allows dependence between null hypotheses. The dependence can be useful to characterize the spatial structure of the null hypotheses. Asymptotic properties of false discovery proportions and numbers of rejected hypotheses are explored and a large-sample distributional theory is obtained.
Factor-adjusted multiple testing is used for handling strong correlated tests. Since most of previous works control the false discovery rate under sparse alternatives, we develop a two-step method, namely the AdaFAT, for any true false proportion. In this paper, the proposed procedure is adjusted by latent factor loadings. Under the existence of explanatory variables, a uniform convergence rate of the estimated factor loadings is given. We also show that the power of AdaFAT goes to one along with the controlled false discovery rate. The performance of the proposed procedure is examined through…
In this paper, a noisy version of the stochastic block model (NSBM) is introduced and we investigate the three following statistical inferences in this model: estimation of the model parameters, clustering of the nodes and identification of the underlying graph. While the two first inferences are done by using a variational expectation-maximization (VEM) algorithm, the graph inference is done by controlling the false discovery rate (FDR), that is, the average proportion of errors among the edges declared significant, and by maximizing the true discovery rate (TDR), that is, the average proport…
In the multiple testing context, a challenging problem is the estimation of the proportion $π_0$ of true-null hypotheses. A large number of estimators of this quantity rely on identifiability assumptions that either appear to be violated on real data, or may be at least relaxed. Under independence, we propose an estimator $\hatπ_0$ based on density estimation using both histograms and cross-validation. Due to the strong connection between the false discovery rate (FDR) and $π_0$, many multiple testing procedures (MTP) designed to control the FDR may be improved by introducing an estimator of $…
University of Southern California（南加州大学）；Stanford University（斯坦福大学）
Multiple hypothesis testing is a core problem in statistical inference and arises in almost every scientific field. Given a set of null hypotheses $\mathcal{H}(n) = (H_1,\dotsc, H_n)$, Benjamini and Hochberg introduced the false discovery rate (FDR), which is the expected proportion of false positives among rejected null hypotheses, and proposed a testing procedure that controls FDR below a pre-assigned significance level. Nowadays FDR is the criterion of choice for large scale multiple hypothesis testing. In this paper we consider the problem of controlling FDR in an "online manner". Concrete…
Much effort has been done to control the "false discovery rate" (FDR) when $m$ hypotheses are tested simultaneously. The FDR is the expectation of the "false discovery proportion" $\text{FDP}=V/R$ given by the ratio of the number of false rejections $V$ and all rejections $R$. In this paper, we have a closer look at the FDP for adaptive linear step-up multiple tests. These tests extend the well known Benjamini and Hochberg test by estimating the unknown amount $m_0$ of the true null hypotheses. We give exact finite sample formulas for higher moments of the FDP and, in particular, for its varia…
Consider the problem of testing $s$ hypotheses simultaneously. The usual approach restricts attention to procedures that control the probability of even one false rejection, the familywise error rate (FWER). If $s$ is large, one might be willing to tolerate more than one false rejection, thereby increasing the ability of the procedure to correctly reject false null hypotheses. One possibility is to replace control of the FWER by control of the probability of $k$ or more false rejections, which is called the $k$-FWER. We derive both single-step and step-down procedures that control the $k$-FWER…
We develop a new class of distribution--free multiple testing rules for false discovery rate (FDR) control under general dependence. A key element in our proposal is a symmetrized data aggregation (SDA) approach to incorporating the dependence structure via sample splitting, data screening and information pooling. The proposed SDA filter first constructs a sequence of ranking statistics that fulfill global symmetry properties, and then chooses a data--driven threshold along the ranking to control the FDR. The SDA filter substantially outperforms the knockoff method in power under moderate to s…
In the multiple testing problem with independent tests, the classical linear step-up procedure controls the false discovery rate (FDR) at level $π_0α$, where $π_0$ is the proportion of true null hypotheses and $α$ is the target FDR level. Adaptive procedures can improve power by incorporating estimates of $π_0$, which typically rely on a tuning parameter. Fixed adaptive procedures set their tuning parameters before seeing the data and can be shown to control the FDR in finite samples. We develop theoretical results for dynamic adaptive procedures whose tuning parameters are determined by the d…
This paper is concerned with false discovery rate (FDR) control in large-scale multiple testing problems. We first propose a new data-driven testing procedure for controlling the FDR in large-scale t-tests for one-sample mean problem. The proposed procedure achieves exact FDR control in finite sample settings when the populations are symmetric no matter the number of tests or sample sizes. Comparing with the existing bootstrap method for FDR control, the proposed procedure is computationally efficient. We show that the proposed method can control the FDR asymptotically for asymmetric populatio…
A resurgence of interest in multiple hypothesis testing has occurred in the last decade. Motivated by studies in genomics, microarrays, DNA sequencing, drug screening, clinical trials, bioassays, education and psychology, statisticians have been devoting considerable research energy in an effort to properly analyze multiple endpoint data. In response to new applications, new criteria and new methodology, many ad hoc procedures have emerged. The classical requirement has been to use procedures which control the strong familywise error rate (FWE) at some predetermined level α. That is, the proba…
We consider the scenario where important signals are not strong enough to be separable from a large amount of noise. Such weak signals commonly exist in large-scale data analysis and play vital roles in many biomedical applications. Existing methods however are mostly underpowered for such weak signals. We address the challenge from the perspective of false negative control and develop a new method to efficiently regulate false negative proportion at a user-specified level. The new method is developed in a realistic setting with arbitrary covariance dependence between variables. We calibrate t…
The False Discovery Rate (FDR) is a commonly used type I error rate in multiple testing problems. It is defined as the expected False Discovery Proportion (FDP), that is, the expected fraction of false positives among rejected hypotheses. When the hypotheses are independent, the Benjamini-Hochberg procedure achieves FDR control at any pre-specified level. By construction, FDR control offers no guarantee in terms of power, or type II error. A number of alternative procedures have been developed, including plug-in procedures that aim at gaining power by incorporating an estimate of the proportio…
Bringing Closure to False Discovery Rate Control: A General Principle for Multiple Testing
Carnegie Mellon University（卡内基梅隆大学）；Ca’ Foscari University of Venice（威尼斯福斯卡里宫大学）；University of Bremen（不来梅大学）；University of Twente（特温特大学）；Centrum Wiskunde & Informatica（荷兰数学与计算机科学研究中心）；Leiden University Medical Center（莱顿大学医学中心）
In many fields of science, we observe a response variable together with a large number of potential explanatory variables, and would like to be able to discover which variables are truly associated with the response. At the same time, we need to know that the false discovery rate (FDR) - the expected fraction of false discoveries among all discoveries - is not too high, in order to assure the scientist that most of the discoveries are indeed true and replicable. This paper introduces the knockoff filter, a new variable selection procedure controlling the FDR in the statistical linear model whe…
Multiple hypothesis testing, a situation when we wish to consider many hypotheses, is a core problem in statistical inference that arises in almost every scientific field. In this setting, controlling the false discovery rate (FDR), which is the expected proportion of type I error, is an important challenge for making meaningful inferences. In this paper, we consider the problem of controlling FDR in an online manner. Concretely, we consider an ordered, possibly infinite, sequence of hypotheses, arriving one at each timestep, and for each hypothesis we observe a p-value along with a set of fea…
In the online multiple testing problem, p-values corresponding to different null hypotheses are observed one by one, and the decision of whether or not to reject the current hypothesis must be made immediately, after which the next p-value is observed. Alpha-investing algorithms to control the false discovery rate (FDR), formulated by Foster and Stine, have been generalized and applied to many settings, including quality-preserving databases in science and multiple A/B or multi-armed bandit tests for internet commerce. This paper improves the class of generalized alpha-investing algorithms (GA…
Multiple hypotheses testing is a core problem in statistical inference and arises in almost every scientific field. Given a sequence of null hypotheses $\mathcal{H}(n) = (H_1,..., H_n)$, Benjamini and Hochberg \cite{benjamini1995controlling} introduced the false discovery rate (FDR) criterion, which is the expected proportion of false positives among rejected null hypotheses, and proposed a testing procedure that controls FDR below a pre-assigned significance level. They also proposed a different criterion, called mFDR, which does not control a property of the realized set of tests; rather it …
In the online false discovery rate (FDR) problem, one observes a possibly infinite sequence of $p$-values $P_1,P_2,\dots$, each testing a different null hypothesis, and an algorithm must pick a sequence of rejection thresholds $α_1,α_2,\dots$ in an online fashion, effectively rejecting the $k$-th null hypothesis whenever $P_k \leq α_k$. Importantly, $α_k$ must be a function of the past, and cannot depend on $P_k$ or any of the later unseen $p$-values, and must be chosen to guarantee that for any time $t$, the FDR up to time $t$ is less than some pre-determined quantity $α\in (0,1)$. In this wo…
