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 thresholds, for controlling the quantiles of the distribution of the FDP as well as controlling the number of false discoveries. We also investigate methods for estimating the p-value distribution.
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.
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.
How to weigh the Benjamini-Hochberg procedure? In the context of multiple hypothesis testing, we propose a new step-wise procedure that controls the false discovery rate (FDR) and we prove it to be more powerful than any weighted Benjamini-Hochberg procedure. Both finite-sample and asymptotic results are presented. Moreover, we illustrate good performance of our procedure in simulations and a genomics application. This work is particularly useful in the case of heterogeneous $p$-value distributions.
Multiple tests are designed to test a whole collection of null hypotheses simultaneously. Their quality is often judged by the false discovery rate (FDR), i.e. the expectation of the quotient of the number of false rejections divided by the amount of all rejections. The widely cited Benjamini and Hochberg (BH) step up multiple test controls the FDR under various regularity assumptions. In this note we present a rapid approach to the BH step up and step down tests. Also sharp FDR inequalities are discussed for dependent p-values and examples and counter-examples are considered. In particular, t…
The false discovery rate (FDR) and false nondiscovery rate (FNDR) have received considerable attention in the literature on multiple testing. These performance measures are also appropriate for classification, and in this work we develop generalization error analyses for FDR and FNDR when learning a classifier from labeled training data. Unlike more conventional classification performance measures, the empirical FDR and FNDR are not binomial random variables but rather a ratio of binomials, which introduces challenges not addressed in conventional analyses. We develop distribution-free uniform…
Modern scientific technology has provided a new class of large-scale simultaneous inference problems, with thousands of hypothesis tests to consider at the same time. Microarrays epitomize this type of technology, but similar situations arise in proteomics, spectroscopy, imaging, and social science surveys. This paper uses false discovery rate methods to carry out both size and power calculations on large-scale problems. A simple empirical Bayes approach allows the false discovery rate (fdr) analysis to proceed with a minimum of frequentist or Bayesian modeling assumptions. Closed-form accurac…
Two major research tasks lie at the heart of high dimensional data analysis: accurate parameter estimation and correct support recovery. The existing literature mostly aims for either the best parameter estimation or the best model selection result, however little has been done to understand the potential interaction between the estimation precision and the selection behavior. In this work, our minimax result shows that an estimator's performance of type I error control directly links with its $L_2$ estimation error rate, and reveals a trade-off phenomenon between the rate of convergence and t…
Results on the false discovery rate (FDR) and the false nondiscovery rate (FNR) are developed for single-step multiple testing procedures. In addition to verifying desirable properties of FDR and FNR as measures of error rates, these results extend previously known results, providing further insights, particularly under dependence, into the notions of FDR and FNR and related measures. First, considering fixed configurations of true and false null hypotheses, inequalities are obtained to explain how an FDR- or FNR-controlling single-step procedure, such as a Bonferroni or uSidák procedure, can …
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…
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 …
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.…
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…
Some effort has been undertaken over the last decade to provide conditions for the control of the false discovery rate by the linear step-up procedure (LSU) for testing $n$ hypotheses when test statistics are dependent. In this paper we investigate the expected error rate (EER) and the false discovery rate (FDR) in some extreme parameter configurations when $n$ tends to infinity for test statistics being exchangeable under null hypotheses. All results are derived in terms of $p$-values. In a general setup we present a series of results concerning the interrelation of Simes' rejection curve and…
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…
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…
The concept of $k$-FWER has received much attention lately as an appropriate error rate for multiple testing when one seeks to control at least $k$ false rejections, for some fixed $k\ge 1$. A less conservative notion, the $k$-FDR, has been introduced very recently by Sarkar [Ann. Statist. 34 (2006) 394--415], generalizing the false discovery rate of Benjamini and Hochberg [J. Roy. Statist. Soc. Ser. B 57 (1995) 289--300]. In this article, we bring newer insight to the $k$-FDR considering a mixture model involving independent $p$-values before motivating the developments of some new procedures…
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…
Efron et al. (2001) proposed empirical Bayes formulation of the frequentist Benjamini and Hochbergs False Discovery Rate method (Benjamini and Hochberg,1995). This article attempts to unify the `two cultures' using concepts of comparison density and distribution function. We have also shown how almost all of the existing local fdr methods can be viewed as proposing various model specification for comparison density - unifies the vast literature of false discovery methods under one concept and notation.
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…
This paper focuses on the influence of a misspecified covariance structure on false discovery rate for the large scale multiple testing problem. Specifically, we evaluate the influence on the marginal distribution of local fdr statistics, which are used in many multiple testing procedures and related to Bayesian posterior probabilities. Explicit forms of the marginal distributions under both correctly specified and incorrectly specified models are derived. The Kullback-Leibler divergence is used to quantify the influence caused by a misspecification. Several numerical examples are provided to …
E-values have gained attention as potential alternatives to p-values as measures of uncertainty, significance and evidence. In brief, e-values are realized by random variables with expectation at most one under the null; examples include betting scores, (point null) Bayes factors, likelihood ratios and stopped supermartingales. We design a natural analog of the Benjamini-Hochberg (BH) procedure for false discovery rate (FDR) control that utilizes e-values, called the e-BH procedure, and compare it with the standard procedure for p-values. One of our central results is that, unlike the usual BH…
The highly influential two-group model in testing a large number of statistical hypotheses assumes that the test statistics are drawn independently from a mixture of a high probability null distribution and a low probability alternative. Optimal control of the marginal false discovery rate (mFDR), in the sense that it provides maximal power (expected true discoveries) subject to mFDR control, is known to be achieved by thresholding the local false discovery rate (locFDR), i.e., the probability of the hypothesis being null given the set of test statistics, with a fixed threshold. We address the…
Multivariate statistics are often available as well as necessary in hypothesis tests. We study how to use such statistics to control not only false discovery rate (FDR) but also positive FDR (pFDR) with good power. We show that FDR can be controlled through nested regions of multivariate $p$-values of test statistics. If the distributions of the test statistics are known, then the regions can be constructed explicitly to achieve FDR control with maximum power among procedures satisfying certain conditions. On the other hand, our focus is where the distributions are only partially known. Under …
We propose a new method, semi-penalized inference with direct false discovery rate control (SPIDR), for variable selection and confidence interval construction in high-dimensional linear regression. SPIDR first uses a semi-penalized approach to constructing estimators of the regression coefficients. We show that the SPIDR estimator is ideal in the sense that it equals an ideal least squares estimator with high probability under a sparsity and other suitable conditions. Consequently, the SPIDR estimator is asymptotically normal. Based on this distributional result, SPIDR determines the selectio…
We propose a general and flexible procedure for testing multiple hypotheses about sequential (or streaming) data that simultaneously controls both the false discovery rate (FDR) and false nondiscovery rate (FNR) under minimal assumptions about the data streams which may differ in distribution, dimension, and be dependent. All that is needed is a test statistic for each data stream that controls the conventional type I and II error probabilities, and no information or assumptions are required about the joint distribution of the statistics or data streams. The procedure can be used with sequenti…
We introduce a new class of methods for finite-sample false discovery rate (FDR) control in multiple testing problems with dependent test statistics where the dependence is fully or partially known. Our approach separately calibrates a data-dependent p-value rejection threshold for each hypothesis, relaxing or tightening the threshold as appropriate to target exact FDR control. In addition to our general framework we propose a concrete algorithm, the dependence-adjusted Benjamini-Hochberg (dBH) procedure, which adaptively thresholds the q-value for each hypothesis. Under positive regression de…
We consider a multiple hypothesis testing setting where the hypotheses are ordered and one is only permitted to reject an initial contiguous block, H_1,\dots,H_k, of hypotheses. A rejection rule in this setting amounts to a procedure for choosing the stopping point k. This setting is inspired by the sequential nature of many model selection problems, where choosing a stopping point or a model is equivalent to rejecting all hypotheses up to that point and none thereafter. We propose two new testing procedures, and prove that they control the false discovery rate in the ordered testing setting. …
The traditional approaches to false discovery rate (FDR) control in multiple hypothesis testing are usually based on the null distribution of a test statistic. However, all types of null distributions, including the theoretical, permutation-based and empirical ones, have some inherent drawbacks. For example, the theoretical null might fail because of improper assumptions on the sample distribution. Here, we propose a null distribution-free approach to FDR control for multiple hypothesis testing. This approach, named target-decoy procedure, simply builds on the ordering of tests by some statist…
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…
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…
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…
Harvard University（哈佛大学）；University of Pennsylvania（宾夕法尼亚大学）；Google Research（谷歌研究院）
Differential privacy provides a rigorous framework for privacy-preserving data analysis. This paper proposes the first differentially private procedure for controlling the false discovery rate (FDR) in multiple hypothesis testing. Inspired by the Benjamini-Hochberg procedure (BHq), our approach is to first repeatedly add noise to the logarithms of the $p$-values to ensure differential privacy and to select an approximately smallest $p$-value serving as a promising candidate at each iteration; the selected $p$-values are further supplied to the BHq and our private procedure releases only the re…
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…
False Discovery Controlled Regions for Excursion Sets
University of California, San Diego（加州大学圣地亚哥分校）；Big Data Institute, Nuffield Department of Population Health, University of Oxford（牛津大学纳菲尔德人口健康学院大数据研究所）；School of Mathematics, University of Bristol（布里斯托尔大学数学学院）；Halıcıoğlu Data Science Institute, University of California, San Diego（加州大学圣地亚哥分校哈奇奥格鲁数据科学研究所）
Motivation: Target-decoy search (TDS) is currently the most popular strategy for estimating and controlling the false discovery rate (FDR) of peptide identifications in mass spectrometry-based shotgun proteomics. While this strategy is very useful in practice and has been intensively studied empirically, its theoretical foundation has not yet been well established. Result: In this work, we systematically analyze the TDS strategy in a rigorous statistical sense. We prove that the commonly used concatenated TDS provides a conservative estimate of the FDR for any given score threshold, but it can…
Georgia Institute of Technology（佐治亚理工学院）；University of Waterloo（滑铁卢大学）
In hypothesis testing, a false discovery occurs when a hypothesis is incorrectly rejected due to noise in the sample. When adaptively testing multiple hypotheses, the probability of a false discovery increases as more tests are performed. Thus the problem of False Discovery Rate (FDR) control is to find a procedure for testing multiple hypotheses that accounts for this effect in determining the set of hypotheses to reject. The goal is to minimize the number (or fraction) of false discoveries, while maintaining a high true positive rate (i.e., correct discoveries). In this work, we study False …
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 article proposes novel rules for false discovery rate control (FDRC) geared towards online anomaly detection in time series. Online FDRC rules allow to control the properties of a sequence of statistical tests. In the context of anomaly detection, the null hypothesis is that an observation is normal and the alternative is that it is anomalous. FDRC rules allow users to target a lower bound on precision in unsupervised settings. The methods proposed in this article overcome short-comings of previous FDRC rules in the context of anomaly detection, in particular ensuring that power remains h…
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…
The positive false discovery rate (pFDR) is a useful overall measure of errors for multiple hypothesis testing, especially when the underlying goal is to attain one or more discoveries. Control of pFDR critically depends on how much evidence is available from data to distinguish between false and true nulls. Oftentimes, as many aspects of the data distributions are unknown, one may not be able to obtain strong enough evidence from the data for pFDR control. This raises the question as to how much data are needed to attain a target pFDR level. We study the asymptotics of the minimum number of o…
Multiple comparison procedures that control a family-wise error rate or false discovery rate provide an achieved error rate as the adjusted p-value for each hypothesis tested. However, since such p-values are not probabilities that the null hypotheses are true, empirical Bayes methods have been devised to estimate such posterior probabilities, called local false discovery rates (LFDRs) to emphasize the frequency interpretation of their priors. The main approaches to LFDR estimation, relying either on numerical algorithms to maximize likelihood or on the selection of smoothing parameters for no…
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…
We provide the first differentially private algorithms for controlling the false discovery rate (FDR) in multiple hypothesis testing, with essentially no loss in power under certain conditions. Our general approach is to adapt a well-known variant of the Benjamini-Hochberg procedure (BHq), making each step differentially private. This destroys the classical proof of FDR control. To prove FDR control of our method, (a) we develop a new proof of the original (non-private) BHq algorithm and its robust variants -- a proof requiring only the assumption that the true null test statistics are indepen…
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…
