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 $π_0$. We provide an example of such an improvement (plug-in MTP) based on the procedure of Benjamini and Hochberg. Asymptotic optimality results may be derived for both $\hatπ_0$ and the resulting plug-in procedure. The latter ensures the desired asymptotic control of the FDR, while it is more powerful than the BH-procedure. Finally, we compare our estimator of $π_0$ with other widespread estimators in a wide range of simulations. We obtain better results than other tested methods in terms of mean square error (MSE) of the proposed estimator. Finally, both asymptotic optimality results and the interest in tightly estimating $π_0$ are confirmed (empirically) by results obtained with the plug-in MTP.
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…
Two recently introduced model based bias corrected estimators for proportion of true null hypotheses ($π_0$) under multiple hypotheses testing scenario have been restructured for exponentially distributed random observations available for each of the common hypotheses. Based on stochastic ordering, a new motivation behind formulation of some related estimators for $π_0$ is given. The reduction of bias for the model based estimators are theoretically justified and algorithms for computing the estimators are also presented. The estimators are also used to formulate a popular adaptive multiple te…
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 consider the problem of estimating the proportion $θ$ of true null hypotheses in a multiple testing context. The setup is classically modeled through a semiparametric mixture with two components: a uniform distribution on interval $[0,1]$ with prior probability $θ$ and a nonparametric density $f$. We discuss asymptotic efficiency results and establish that two different cases occur whether $f$ vanishes on a set with non null Lebesgue measure or not. In the first case, we exhibit estimators converging at parametric rate, compute the optimal asymptotic variance and conjecture that no estimato…
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 with false discovery rate (FDR) control when p-values have discrete and heterogeneous null distributions. We propose a new estimator of the proportion of true null hypotheses and demonstrate that it is less upwardly biased than Storey's estimator and two other estimators. The new estimator induces two adaptive procedures, i.e., an adaptive Benjamini-Hochberg (BH) procedure and an adaptive Benjamini-Hochberg-Heyse (BHH) procedure. We prove that the the adaptive BH procedure is conservative non-asymptotically. Through simulation studies, we show that these procedures…
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 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…
Weighting the p-values is a well-established strategy that improves the power of multiple testing procedures while dealing with heterogeneous data. However, how to achieve this task in an optimal way is rarely considered in the literature. This paper contributes to fill the gap in the case of group-structured null hypotheses, by introducing a new class of procedures named ADDOW (for Adaptive Data Driven Optimal Weighting) that adapts both to the alternative distribution and to the proportion of true null hypotheses. We prove the asymptotical FDR control and power optimality among all weighted …
Some crucial issues about a recently proposed estimator for the proportion of true null hypotheses ($π_0$) under discrete setup are discussed. An estimator for $π_0$ is introduced under the same setup. The estimator may be seen as a modification of a very popular estimator for $π_0$, originally proposed under the assumption of continuous test statistics. It is shown that adaptive Benjamini-Hochberg procedure remains conservative with the new estimator for $π_0$ being plugged in.
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…
We propose a permutation-based method for testing a large collection of hypotheses simultaneously. Our method provides lower bounds for the number of true discoveries in any selected subset of hypotheses. These bounds are simultaneously valid with high confidence. The methodology is particularly useful in functional Magnetic Resonance Imaging cluster analysis, where it provides a confidence statement on the percentage of truly activated voxels within clusters of voxels, avoiding the well-known spatial specificity paradox. We offer a user-friendly tool to estimate the percentage of true discove…
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…
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 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.…
In the context of multiple hypotheses testing, the proportion $π_0$ of true null hypotheses in the pool of hypotheses to test often plays a crucial role, although it is generally unknown a priori. A testing procedure using an implicit or explicit estimate of this quantity in order to improve its efficency is called adaptive. In this paper, we focus on the issue of False Discovery Rate (FDR) control and we present new adaptive multiple testing procedures with control of the FDR. First, in the context of assuming independent $p$-values, we present two new procedures and give a unified review of …
Positive--unlabeled (PU) learning considers two samples, a positive set P with observations from only one class and an unlabeled set U with observations from two classes. The goal is to classify observations in U. Class mixture proportion estimation (MPE) in U is a key step in PU learning. Blanchard et al. [2010] showed that MPE in PU learning is a generalization of the problem of estimating the proportion of true null hypotheses in multiple testing problems. Motivated by this idea, we propose reducing the problem to one dimension via construction of a probabilistic classifier trained on the P…
A new formulation for the proportion of true null hypotheses $(π_0)$, based on the sum of all $p$-values and the average of expected $p$-value under the false null hypotheses has been proposed in the current work. This formulation of the parameter of interest $π_0$ has also been used to construct a new estimator for the same. The proposed estimator removes the problem of choosing tuning parameters in the existing estimators. Though the formulation is quite general, computation of the new estimator demands use of an initial estimate of $π_0$. The issue of choosing an appropriate initial estimat…
We are concerned with testing replicability hypotheses for many endpoints simultaneously. This constitutes a multiple test problem with composite null hypotheses. Traditional $p$-values, which are computed under least favourable parameter configurations, are over-conservative in the case of composite null hypotheses. As demonstrated in prior work, this poses severe challenges in the multiple testing context, especially when one goal of the statistical analysis is to estimate the proportion $π_0$ of true null hypotheses. Randomized $p$-values have been proposed to remedy this issue. In the pres…
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…
We consider the decentralized binary hypothesis testing problem on trees of bounded degree and increasing depth. For a regular tree of depth t and branching factor k>=2, we assume that the leaves have access to independent and identically distributed noisy observations of the 'state of the world' s. Starting with the leaves, each node makes a decision in a finite alphabet M, that it sends to its parent in the tree. Finally, the root decides between the two possible states of the world based on the information it receives. We prove that the error probability vanishes only subexponentially in th…
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 …
We consider the problem of inference on a regression function at a point when the entire function satisfies a sign or shape restriction under the null. We propose a test that achieves the optimal minimax rate adaptively over a range of Hölder classes, up to a $\log\log n$ term, which we show to be necessary for adaptation. We apply the results to adaptive one-sided tests for the regression discontinuity parameter under a monotonicity restriction, the value of a monotone regression function at the boundary and the proportion of true null hypotheses in a multiple testing problem.
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）
This paper studies the high-dimensional mixed linear regression (MLR) where the output variable comes from one of the two linear regression models with an unknown mixing proportion and an unknown covariance structure of the random covariates. Building upon a high-dimensional EM algorithm, we propose an iterative procedure for estimating the two regression vectors and establish their rates of convergence. Based on the iterative estimators, we further construct debiased estimators and establish their asymptotic normality. For individual coordinates, confidence intervals centered at the debiased …
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 …
Nowadays, beta and Kumaraswamy distributions are the most popular models to fit continuous bounded data. These models present some characteristics in common and to select one of them in a practical situation can be of great interest. With this in mind, in this paper we propose a method of selection between the beta and Kumaraswamy distributions. We use the logarithm of the likelihood ratio statistic (denoted by $T_n$, where $n$ is the sample size) and obtain its asymptotic distribution under the hypotheses $H_{\mathcal B}$ and $H_{\mathcal K}$, where $H_{\mathcal B}$ ($H_{\mathcal K}$) denotes…
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…
When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate (FDR) assume that all p-values are available at the time point of test decision. In platform trials, however, treatment arms enter and leave the trial at any time during its conduct. Therefore, the number of treatments and hypothesis tests is not fixed in advance and hypotheses are not tested at once, but sequentially. Recently, for such a setting the concept of online control of the FDR was introduced. We investigate the LOND procedu…
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…
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…
The Benjamini-Hochberg (BH) procedure is a celebrated method for multiple testing with false discovery rate (FDR) control. In this paper, we consider large-scale distributed networks where each node possesses a large number of p-values and the goal is to achieve the global BH performance in a communication-efficient manner. We propose that every node performs a local test with an adjusted test size according to the (estimated) global proportion of true null hypotheses. With suitable assumptions, our method is asymptotically equivalent to the global BH procedure. Motivated by this, we develop a…
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.
The proportional hazards assumption in the commonly used Cox model for censored failure time data is often violated in scientific studies. Yang and Prentice (2005) proposed a novel semiparametric two-sample model that includes the proportional hazards model and the proportional odds model as sub-models, and accommodates crossing survival curves. The model leaves the baseline hazard unspecified and the two model parameters can be interpreted as the short-term and long-term hazard ratios. Inference procedures were developed based on a pseudo score approach. Although extension to accommodate cova…
Motivation: Combining the results of different experiments to exhibit complex patterns or to improve statistical power is a typical aim of data integration. The starting point of the statistical analysis often comes as sets of p-values resulting from previous analyses, that need to be combined in a flexible way to explore complex hypotheses, while guaranteeing a low proportion of false discoveries. Results: We introduce the generic concept of composed hypothesis, which corresponds to an arbitrary complex combination of simple hypotheses. We rephrase the problem of testing a composed hypothesis…
By restricting the possible values of the proportion of null hypotheses that are true, the local false discovery rate (LFDR) can be estimated using as few as one comparison. The proportion of proteins with equivalent abundance was estimated to be about 20% for patient group I and about 90% for group II. The simultaneously-estimated LFDRs give approximately the same inferences as individual-protein confidence levels for group I but are much closer to individual-protein LFDR estimates for group II. Simulations confirm that confidence-based inference or LFDR-based inference performs markedly bett…
The Weather Risk Attribution Forecast (WRAF) is a forecasting tool that uses output from global climate models to make simultaneous attribution statements about whether and how greenhouse gas emissions have contributed to extreme weather across the globe. However, in conducting a large number of simultaneous hypothesis tests, the WRAF is prone to identifying false "discoveries." A common technique for addressing this multiple testing problem is to adjust the procedure in a way that controls the proportion of true null hypotheses that are incorrectly rejected, or the false discovery rate (FDR).…
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 …
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…
Correlated proportions arise in longitudinal (panel) studies. A typical example is the ``opinion swing'' problem: ``Has the proportion of people favoring a politician changed after his recent speech to the nation on TV?''. Since the same group of individuals is interviewed before and after the speech, the two proportions are correlated. A natural null hypothesis to be tested is whether the corresponding population proportions are equal. A standard Bayesian approach to this problem has already been considered in the literature, based on a Dirichlet prior for the cell-probabilities of the underl…
