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.f. of the $p$-values. We also derive explicit computations of the power for both step-up and step-down procedures. These formulas are "explicit" in the sense that they only involve the parameters of the model and the c.d.f. of the order statistics of i.i.d. uniform variables. The $p$-values are assumed either independent or coming from an equicorrelated multivariate normal model and an additional mixture model for the true/false hypotheses is used. This new approach is used to investigate new results which are of interest in their own right, related to least/most favorable configurations for the FDR and the variance of the FDP.
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…
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…
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…
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] …
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…
Closed testing procedures are classically used for familywise error rate (FWER) control, but they can also be used to obtain simultaneous confidence bounds for the false discovery proportion (FDP) in all subsets of the hypotheses. In this paper we investigate the special case of closed testing with Simes local tests. We construct a novel fast and exact shortcut which we use to investigate the power of this method when the number of hypotheses goes to infinity. We show that, if a minimal amount of signal is present, the average power to detect false hypotheses at any desired FDP level does not …
We consider multiple testing means of many dependent Normal random variables that do not necessarily follow a joint Normal distribution. Under weak dependence, we show the uniform consistency of proportion estimators that are constructed as solutions to Lebesgue-Stieltjes equations for the setting of a point, bounded and one-sided null, respectively, and characterize via the index of weak dependence the sparsest proportion these estimators can consistently estimate. On the other hand, under a principal correlation structure and employing a suitable definition of p-value for composite null hypo…
Large-scale multiple testing with highly correlated test statistics arises frequently in many scientific research. Incorporating correlation information in estimating false discovery proportion has attracted increasing attention in recent years. When the covariance matrix of test statistics is known, Fan, Han & Gu (2012) provided a consistent estimate of False Discovery Proportion (FDP) under arbitrary dependence structure. However, the covariance matrix is often unknown in many applications and such dependence information has to be estimated before estimating FDP (Efron, 2010). The estimation…
When multiple hypotheses are tested, interest is often in ensuring that the proportion of false discoveries (FDP) is small with high confidence. In this paper, confidence upper bounds for the FDP are constructed, which are simultaneous over all rejection cut-offs. In particular this allows the user to select a set of hypotheses post hoc such that the FDP lies below some constant with high confidence. Our method uses permutations to account for the dependence structure in the data. So far only Meinshausen provided an exact, permutation-based and computationally feasible method for simultaneous …
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…
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…
We propose an adaptive sampling approach for multiple testing which aims to maximize statistical power while ensuring anytime false discovery control. We consider $n$ distributions whose means are partitioned by whether they are below or equal to a baseline (nulls), versus above the baseline (actual positives). In addition, each distribution can be sequentially and repeatedly sampled. Inspired by the multi-armed bandit literature, we provide an algorithm that takes as few samples as possible to exceed a target true positive proportion (i.e. proportion of actual positives discovered) while givi…
Everywhere Valid Bounds on False Discovery Proportions in Conformal Inference
Department of Statistics, Stanford University（斯坦福大学统计学系）；Department of Statistics and Data Science, University of Pennsylvania（宾夕法尼亚大学统计学与数据科学系）；Department of Mathematics, Stanford University（斯坦福大学数学系）
Post hoc false discovery proportion inference under a Hidden Markov Model
Université de Paris, CNRS（巴黎大学）；Université Paris-Saclay, CNRS, Inria Laboratoire de mathématiques d’Orsay（巴黎萨克雷大学）；Institut de Mathématiques de Toulouse UMR 5219, Université de Toulouse, CNRS UPS（图卢兹数学研究所）；Laboratoire de Probabilités, Statistique et Modélisation, Sorbonne Université, Université de Paris, CNRS（索邦大学）
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…
This research deals with massive multiple hypothesis testing. First regarding multiple tests as an estimation problem under a proper population model, an error measurement called Erroneous Rejection Ratio (ERR) is introduced and related to the False Discovery Rate (FDR). ERR is an error measurement similar in spirit to FDR, and it greatly simplifies the analytical study of error properties of multiple test procedures. Next an improved estimator of the proportion of true null hypotheses and a data adaptive significance threshold criterion are developed. Some asymptotic error properties of the s…
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.
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…
Statistical dependence between hypotheses poses a significant challenge to the stability of large scale multiple hypotheses testing. Ignoring it often results in an unacceptably large spread in the false positive proportion even though the average value is acceptable [21, 39, 40, 49]. However, the statistical dependence structure of data is often unknown. Using a generic signalprocessing model, Bayesian multiple testing, and simulations, we demonstrate that the variance of the false positive proportion can be substantially reduced even under unknown short range dependence. We do this by modeli…
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 presents a survey on some recent advances for the type I error rate control in multiple testing methodology. We consider the problem of controlling the $k$-family-wise error rate (kFWER, probability to make $k$ false discoveries or more) and the false discovery proportion (FDP, proportion of false discoveries among the discoveries). The FDP is controlled either via its expectation, which is the so-called false discovery rate (FDR), or via its upper-tail distribution function. We aim at deriving general and unified results together with concise and simple mathematical proofs. Further…
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…
An important estimation problem that is closely related to large-scale multiple testing is that of estimating the null density and the proportion of nonnull effects. A few estimators have been introduced in the literature; however, several important problems, including the evaluation of the minimax rate of convergence and the construction of rate-optimal estimators, remain open. In this paper, we consider optimal estimation of the null density and the proportion of nonnull effects. Both minimax lower and upper bounds are derived. The lower bound is established by a two-point testing argument, …
This article considers the problem of multiple hypothesis testing using $t$-tests. The observed data are assumed to be independently generated conditional on an underlying and unknown two-state hidden model. We propose an asymptotically valid data-driven procedure to find critical values for rejection regions controlling the $k$-familywise error rate ($k$-FWER), false discovery rate (FDR) and the tail probability of false discovery proportion (FDTP) by using one-sample and two-sample $t$-statistics. We only require a finite fourth moment plus some very general conditions on the mean and varian…
This paper investigates an open issue related to false discovery rate (FDR) control of step-up-down (SUD) multiple testing procedures. It has been established in earlier literature that for this type of procedure, under some broad conditions, and in an asymptotical sense, the FDR is maximum when the signal strength under the alternative is maximum. In other words, so-called "Dirac uniform configurations" are asymptotically {\em least favorable} in this setting. It is known that this property also holds in a non-asymptotical sense (for any finite number of hypotheses), for the two extreme versi…
Large-scale multiple testing with correlated and heavy-tailed data arises in a wide range of research areas from genomics, medical imaging to finance. Conventional methods for estimating the false discovery proportion (FDP) often ignore the effect of heavy-tailedness and the dependence structure among test statistics, and thus may lead to inefficient or even inconsistent estimation. Also, the commonly imposed joint normality assumption is arguably too stringent for many applications. To address these challenges, in this paper we propose a Factor-Adjusted Robust Multiple Testing (FarmTest) proc…
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 $…
The high fraction of published results that turn out to be incorrect is a major concern of today's science. This paper contributes to the understanding of this problem in two independent directions. First, Johnson's recent claim that hypothesis testing with a significance level of 0.05 can alone lead to an unacceptably large proportion of false positives among all results is shown to be unfounded. Second, a way to quantify the effect of "positivity bias" (the tendency to consider only positive results as worthwhile) is introduced. We estimate the proportion of false positives among positive re…
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…
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…
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…
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…
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 $\mathit{FWER}$. …
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 …
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）
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 genes 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 new methodology based on principal factor approximation, which successfully substracts the common dependence and weakens significantly the c…
Efforts to develop more efficient multiple hypothesis testing procedures for false discovery rate (FDR) control have focused on incorporating an estimate of the proportion of true null hypotheses (such procedures are called adaptive) or exploiting heterogeneity across tests via some optimal weighting scheme. This paper combines these approaches using a weighted adaptive multiple decision function (WAMDF) framework. Optimal weights for a flexible random effects model are derived and a WAMDF that controls the FDR for arbitrary weighting schemes when test statistics are independent under the null…
False discovery rates (FDR) are an essential component of statistical inference, representing the propensity for an observed result to be mistaken. FDR estimates should accompany observed results to help the user contextualize the relevance and potential impact of findings. This paper introduces a new user-friendly R package for computing FDRs and adjusting p-values for FDR control. These tools respect the critical difference between the adjusted p-value and the estimated FDR for a particular finding, which are sometimes numerically identical but are often confused in practice. Newly augmented…
We propose a new empirical Bayes method for covariate-assisted multiple testing with false discovery rate (FDR) control, where we model the local false discovery rate for each hypothesis as a function of both its covariates and p-value. Our method refines the adaptive p-value thresholding (AdaPT) procedure by generalizing its masking scheme to reduce the bias and variance of its false discovery proportion estimator, improving the power when the rejection set is small or some null p-values concentrate near 1. We also introduce a Gaussian mixture model for the conditional distribution of the tes…
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 …
Penalized likelihood inference for beta-binomial meta-analysis of proportions of rare events
The Graduate Institute for Advanced Studies, The Graduate University for Advanced Studies（高级研究研究生院，高级研究院）；Department of Interdisciplinary Statistical Mathematics, The Institute of Statistical Mathematics（统计数学系，统计数学研究所）
This paper continues the line of research initiated in Liu et. al. (2016) on developing a novel framework for multiple testing of hypotheses grouped in a one-way classified form using hypothesis-specific local false discovery rates (Lfdr's). It is built on an extension of the standard two-class mixture model from single to multiple groups, defining hypothesis-specific Lfdr as a function of the conditional Lfdr for the hypothesis given that it is within an important group and the Lfdr for the group itself and involving a new parameter that measures grouping effect. This definition captures the …
