We study the problem of estimating the distribution of effect sizes (the mean of the test statistic under the alternate hypothesis) in a multiple testing setting. Knowing this distribution allows us to calculate the power (type II error) of any experimental design. We show that it is possible to estimate this distribution using an inexpensive pilot experiment, which takes significantly fewer samples than would be required by an experiment that identified the discoveries. Our estimator can be used to guarantee the number of discoveries that will be made using a given experimental design in a future experiment. We prove that this simple and computationally efficient estimator enjoys a number of favorable theoretical properties, and demonstrate its effectiveness on data from a gene knockout experiment on influenza inhibition in Drosophila.
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…
Global hypothesis tests are a useful tool in the context of, e.g, clinical trials, genetic studies or meta analyses, when researchers are not interested in testing individual hypotheses, but in testing whether none of the hypotheses is false. There are several possibilities how to test the global null hypothesis when the individual null hypotheses are independent. If it is assumed that many of the individual null hypotheses are false, combinations tests have been recommended to maximise power. If, however, it is assumed that only one or a few null hypotheses are false, global tests based on in…
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…
Fisherian randomization inference is often dismissed as testing an uninteresting and implausible hypothesis: the sharp null of no effects whatsoever. We show that this view is overly narrow. Many randomization tests are also valid under a more general "bounded" null hypothesis under which all effects are weakly negative (or positive), thus accommodating heterogenous effects. By inverting such tests we can form one-sided confidence intervals for the maximum (or minimum) effect. These properties hold for all effect-increasing test statistics, which include both common statistics such as the mean…
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…
False discovery rate (FDR) controlling procedures provide important statistical guarantees for the replicability in signal identification based on multiple hypotheses testing. In many fields of study, FDR controlling procedures are used in high-dimensional (HD) analyses to discover features that are truly associated with the outcome. In some recent applications, data on the same set of candidate features are independently collected in multiple different studies. For example, gene expression data are collected at different facilities and with different cohorts, to identify the genetic biomarker…
When there is a suspicious figure reuse case in science, research integrity investigators often find it difficult to rebut authors claiming that "it happened by chance". In other words, when there is a "collision" of image features, it is difficult to justify whether it appears rarely or not. In this article, we provide a method to predict the rarity of an image feature by statistically estimating the chance of it randomly occurring across all scientific imagery. Our method is based on high-dimensional density estimation of ORB features using 7+ million images in the PubMed Open Access Subset …
We consider statistical hypothesis testing simultaneously over a fairly general, possibly uncountably infinite, set of null hypotheses, under the assumption that a suitable single test (and corresponding $p$-value) is known for each individual hypothesis. We extend to this setting the notion of false discovery rate (FDR) as a measure of type I error. Our main result studies specific procedures based on the observation of the $p$-value process. Control of the FDR at a nominal level is ensured either under arbitrary dependence of $p$-values, or under the assumption that the finite dimensional di…
The goal of mediation analysis is to study the effect of exposure on an outcome interceded by a mediator. Two simple hypotheses are tested: the effect of the exposure on the mediator, and the effect of the mediator on the outcome. When either of these hypotheses is true, a predetermined significance level can be assured. When both nulls are true, the same test becomes conservative. Adaptively finding the correct scenario enables customizing the tests and consequently enlarges their efficiency, which is most important in a multiple testing framework. In this work, we link between adaptive two-s…
In many practical applications of multiple hypothesis testing using the False Discovery Rate (FDR), the given hypotheses can be naturally partitioned into groups, and one may not only want to control the number of false discoveries (wrongly rejected null hypotheses), but also the number of falsely discovered groups of hypotheses (we say a group is falsely discovered if at least one hypothesis within that group is rejected, when in reality the group contains only nulls). In this paper, we introduce the p-filter, a procedure which unifies and generalizes the standard FDR procedure by Benjamini a…
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…
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 $…
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…
$P$-values that are derived from continuously distributed test statistics are typically uniformly distributed on $(0,1)$ under least favorable parameter configurations (LFCs) in the null hypothesis. Conservativeness of a $p$-value $P$ (meaning that $P$ is under the null hypothesis stochastically larger than a random variable which is uniformly distributed on $(0,1)$) can occur if the test statistic from which $P$ is derived is discrete, or if the true parameter value under the null is not an LFC. To deal with both of these sources of conservativeness, we present two approaches utilizing random…
Randomization tests are based on a re-randomization of existing data to gain data-dependent critical values that lead to exact hypothesis tests under special circumstances. However, it is not always possible to re-randomize data in accordance to the physical randomization from which the data has been obained. As a consequence, most statistical tests cannot control the type I error probability. Still, similarly as the bootstrap, data re-randomization can be used to improve the type I error control. However, no general asymptotic theory under weak null hypotheses has been developed for such rand…
In many fields of research null hypothesis significance tests and p values are the accepted way of assessing the degree of certainty with which research results can be extrapolated beyond the sample studied. However, there are very serious concerns about the suitability of p values for this purpose. An alternative approach is to cite confidence intervals for a statistic of interest, but this does not directly tell readers how certain a hypothesis is. Here, I suggest how the framework used for confidence intervals could easily be extended to derive confidence levels, or "tentative probabilities…
IDSIA/SUPSI；Università della Svizzera Italiana（瑞士意大利语区大学）；Vita-Salute San Raffaele University（圣拉斐尔生命健康大学）；Ruhr-Universität Bochum（波鸿鲁尔大学）；Université de Sherbrooke（舍布鲁克大学）
Do two data samples come from different distributions? Recent studies of this fundamental problem focused on embedding probability distributions into sufficiently rich characteristic Reproducing Kernel Hilbert Spaces (RKHSs), to compare distributions by the distance between their embeddings. We show that Regularized Maximum Mean Discrepancy (RMMD), our novel measure for kernel-based hypothesis testing, yields substantial improvements even when sample sizes are small, and excels at hypothesis tests involving multiple comparisons with power control. We derive asymptotic distributions under the n…
The main purpose of this paper is to introduce first a new family of empirical test statistics for testing a simple null hypothesis when the vector of parameters of interest are defined through a specific set of unbiased estimating functions. This family of test statistics is based on a distance between two probability vectors, with the first probability vector obtained by maximizing the empirical likelihood on the vector of parameters, and the second vector defined from the fixed vector of parameters under the simple null hypothesis. The distance considered for this purpose is the phi-diverge…
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…
There is a significant literature on methods for incorporating knowledge into multiple testing procedures so as to improve their power and precision. Some common forms of prior knowledge include (a) beliefs about which hypotheses are null, modeled by non-uniform prior weights; (b) differing importances of hypotheses, modeled by differing penalties for false discoveries; (c) multiple arbitrary partitions of the hypotheses into (possibly overlapping) groups; and (d) knowledge of independence, positive or arbitrary dependence between hypotheses or groups, suggesting the use of more aggressive or …
In a recent paper (Efron (2004)), Efron pointed out that an important issue in large-scale multiple hypothesis testing is that the null distribution may be unknown and need to be estimated. Consider a Gaussian mixture model, where the null distribution is known to be normal but both null parameters--the mean and the variance--are unknown. We address the problem with a method based on Fourier transformation. The Fourier approach was first studied by Jin and Cai (2007), which focuses on the scenario where any non-null effect has either the same or a larger variance than that of the null effects.…
Graphical tests assess whether a function of interest departs from an envelope of functions generated under a simulated null distribution. This approach originated in spatial statistics, but has recently gained some popularity in functional data analysis. Whereas such envelope tests examine deviation from a functional null distribution in an omnibus sense, in some applications we wish to do more: to obtain p-values at each point in the function domain, adjusted to control the familywise error rate. Here we derive pointwise adjusted p-values based on envelope tests, and relate these to previous…
It is well-known that in some situations it is not easy to compute the likelihood function as the datasets might be large or the model is too complex. In that contexts composite likelihood, derived by multiplying the likelihoods of subjects of the variables, may be useful. The extension of the classical likelihood ratio test statistics to the framework of composite likelihoods is used as a procedure to solve the problem of testing in the context of composite likelihood. In this paper we introduce and study a new family of test statistics for composite likelihood: Composite ϕ-divergence test st…
We consider the problem of the construction of the Goodness-of-Fit test in the case of continuous time observations of a diffusion process with small noise. The null hypothesis is parametric and we use a minimum distance estimator of the unknown parameter. We propose an asymptotically distribution free test for this model.
In a novel approach to the multiple testing problem, Efron (2004; 2007) formulated estimators of the distribution of test statistics or nominal p-values under a null distribution suitable for modeling the data of thousands of unaffected genes, non-associated single-nucleotide polymorphisms, or other biological features. Estimators of the null distribution can improve not only the empirical Bayes procedure for which it was originally intended, but also many other multiple comparison procedures. Such estimators serve as the groundwork for the proposed multiple comparison procedure based on a rec…
In a high dimensional multiple testing framework, we present new confidence bounds on the false positives contained in subsets S of selected null hypotheses. The coverage probability holds simultaneously over all subsets S, which means that the obtained confidence bounds are post hoc. Therefore, S can be chosen arbitrarily, possibly by using the data set several times. We focus in this paper specifically on the case where the null hypotheses are spatially structured. Our method is based on recent advances in post hoc inference and particularly on the general methodology of Blanchard et al. (20…
The general philosophy for bootstrap or permutation methods for testing hypotheses is to simulate the variation of the test statistic by generating the sampling distribution which assumes both that the null hypothesis is true, and that the data in the sample is somehow representative of the population. This philosophy is inapplicable for testing hypotheses for a single parameter like the population mean, since the two assumptions are contradictory (e.g., how can we assume both that the mean of the population is $μ_0,$ and that the individuals in the sample with a mean $M \ne μ_0$ are represent…
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…
Null Hypothesis Significance Testing (NHST) has long been of central importance to psychology as a science, guiding theory development and underlying the application of evidence-based intervention and decision-making. Recent years, however, have seen growing awareness of serious problems with NHST as it is typically used; this awareness has led to proposals to limit the use of NHST techniques, to abandon these techniques and move to alternative statistical approaches, or even to ban the use of NHST entirely. These proposals are premature, because the observed problems with NHST arise as a cons…
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 …
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…
Many multiple testing procedures make use of the p-values from the individual pairs of hypothesis tests, and are valid if the p-value statistics are independent and uniformly distributed under the null hypotheses. However, it has recently been shown that these types of multiple testing procedures are inefficient since such p-values do not depend upon all of the available data. This paper provides tools for constructing compound p-value statistics, which are those that depend upon all of the available data, but still satisfy the conditions of independence and uniformity under the null hypothese…
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, …
Null hypothesis significance tests and p values are widely used despite very strong arguments against their use in many contexts. Confidence intervals are often recommended as an alternative, but these do not achieve the objective of assessing the credibility of a hypothesis, and the distinction between confidence and probability is an unnecessary confusion. This paper proposes a more straightforward (probabilistic) definition of confidence, and suggests how the idea can be applied to whatever hypotheses are of interest to researchers. The relative merits of the different approaches are discus…
This paper proposes novel tests for the absence of jumps in a univariate semimartingale and for the absence of common jumps in a bivariate semimartingale. Our methods rely on ratio statistics of power variations based on irregular observations, sampled at different frequencies. We develop central limit theorems for the statistics under the respective null hypotheses and apply bootstrap procedures to assess the limiting distributions. Further we define corrected statistics to improve the finite sample performance. Simulations show that the test based on our corrected statistic yields good resul…
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 …
Scientists often adjust their significance threshold (alpha level) during null hypothesis significance testing in order to take into account multiple testing and multiple comparisons. This alpha adjustment has become particularly relevant in the context of the replication crisis in science. The present article considers the conditions in which this alpha adjustment is appropriate and the conditions in which it is inappropriate. A distinction is drawn between three types of multiple testing: disjunction testing, conjunction testing, and individual testing. It is argued that alpha adjustment is …
In many statistical problems the hypotheses are naturally divided into groups, and the investigators are interested to perform group-level inference, possibly along with inference on individual hypotheses. We consider the goal of discovering groups containing $u$ or more signals with group-level false discovery rate (FDR) control. This goal can be addressed by multiple testing of partial conjunction hypotheses with a parameter $u,$ which reduce to global null hypotheses for $u=1.$ We consider the case where the partial conjunction $p$-values are combinations of within-group $p$-values, and obt…
Current statistical inference problems in areas like astronomy, genomics, and marketing routinely involve the simultaneous testing of thousands -- even millions -- of null hypotheses. For high-dimensional multivariate distributions, these hypotheses may concern a wide range of parameters, with complex and unknown dependence structures among variables. In analyzing such hypothesis testing procedures, gains in efficiency and power can be achieved by performing variable reduction on the set of hypotheses prior to testing. We present in this paper an approach using data-adaptive multiple testing t…
Recently, several authors have re-examined the power of the classical F-test in linear regression in a `large-p, large-n' framework (cf. Zhong and Chen (2011), Wang and Cui (2013)). They highlight the loss of power as the number of regressors p increases relative to sample size n. These papers essentially focus only on the overall test of the null hypothesis that all p slope coefficients are equal to zero. Here, we consider the general case of testing q linear hypotheses on the (p+1)-dimensional regression parameter vector that includes p slope coefficients and an intercept parameter. In the c…
Large-scale multiple testing is a fundamental problem in high dimensional statistical inference. It is increasingly common that various types of auxiliary information, reflecting the structural relationship among the hypotheses, are available. Exploiting such auxiliary information can boost statistical power. To this end, we propose a framework based on a two-group mixture model with varying probabilities of being null for different hypotheses a priori, where a shape-constrained relationship is imposed between the auxiliary information and the prior probabilities of being null. An optimal reje…
