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Phylogenetic association analysis plays a crucial role in investigating the correlation between microbial compositions and specific outcomes of interest in microbiome studies. However, existing methods for testing such associations have limitations related to the assumption of a linear association in high-dimensional settings and the handling of confounding effects. Hence, there is a need for methods capable of characterizing complex associations, including nonmonotonic relationships. This article introduces a novel phylogenetic association analysis framework and associated tests to address these challenges by employing conditional rank correlation as a measure of association. The proposed tests account for confounders in a fully nonparametric manner, ensuring robustness against outliers and the ability to detect diverse dependencies. The proposed framework aggregates conditional rank correlations for subtrees using weighted sum and maximum approaches to capture both dense and sparse signals. The significance level of the test statistics is determined by calibration through a nearest-neighbour bootstrapping method, which is straightforward to implement and can accommodate additional datasets when these are available. The practical advantages of the proposed framework are demonstrated through numerical experiments using both simulated and real microbiome datasets. [ABSTRACT FROM AUTHOR]

Generalized linear models often have high-dimensional nuisance parameters, as seen in applications such as testing gene-environment interactions or gene-gene interactions. In these scenarios, it is essential to test the significance of a high-dimensional subvector of the model's coefficients. Although some existing methods can tackle this problem, they often rely on the bootstrap to approximate the asymptotic distribution of the test statistic, and are thus computationally expensive. Here, we propose a computationally efficient test with a closed-form limiting distribution, which allows the parameter being tested to be either sparse or dense. We show that, under certain regularity conditions, the Type-I error of the proposed method is asymptotically correct, and we establish its power under high-dimensional alternatives. Extensive simulations demonstrate the good performance of the proposed test and its robustness when certain sparsity assumptions are violated. We also apply the proposed method to Chinese famine sample data in order to show its performance when testing the significance of gene-environment interactions. [ABSTRACT FROM AUTHOR]

We consider the problem of testing for the presence of linear relationships between large sets of random variables based on a postselection inference approach to canonical correlation analysis. The challenge is to adjust for the selection of subsets of variables having linear combinations with maximal sample correlation. To this end, we construct a stabilized one-step estimator of the Euclidean norm of the canonical correlations maximized over subsets of variables of prespecified cardinality. This estimator is shown to be consistent for its target parameter and asymptotically normal, provided the dimensions of the variables do not grow too quickly with sample size. We also develop a greedy search algorithm to accurately compute the estimator, leading to a computationally tractable omnibus test for the global null hypothesis that there are no linear relationships between any subsets of variables having the prespecified cardinality. We further develop a confidence interval that takes the variable selection into account. [ABSTRACT FROM AUTHOR]

Identifying dependency in multivariate data is a common inference task that arises in numerous applications. However, existing nonparametric independence tests typically require computation that scales at least quadratically with the sample size, making it difficult to apply them in the presence of massive sample sizes. Moreover, resampling is usually necessary to evaluate the statistical significance of the resulting test statistics at finite sample sizes, further worsening the computational burden. We introduce a scalable, resampling-free approach to testing the independence between two random vectors by breaking down the task into simple univariate tests of independence on a collection of |$2\times 2$| contingency tables constructed through sequential coarse-to-fine discretization of the sample , transforming the inference task into a multiple testing problem that can be completed with almost linear complexity with respect to the sample size. To address increasing dimensionality, we introduce a coarse-to-fine sequential adaptive procedure that exploits the spatial features of dependency structures. We derive a finite-sample theory that guarantees the inferential validity of our adaptive procedure at any given sample size. We show that our approach can achieve strong control of the level of the testing procedure at any sample size without resampling or asymptotic approximation and establish its large-sample consistency. We demonstrate through an extensive simulation study its substantial computational advantage in comparison to existing approaches while achieving robust statistical power under various dependency scenarios, and illustrate how its divide-and-conquer nature can be exploited to not just test independence, but to learn the nature of the underlying dependency. Finally, we demonstrate the use of our method through analysing a dataset from a flow cytometry experiment. [ABSTRACT FROM AUTHOR]

Probability forecasts for binary events play a central role in many applications. Their quality is commonly assessed with proper scoring rules, which assign forecasts numerical scores such that a correct forecast achieves a minimal expected score. In this paper, we construct e-values for testing the statistical significance of score differences of competing forecasts in sequential settings. E-values have been proposed as an alternative to |$p$| -values for hypothesis testing, and they can easily be transformed into conservative |$p$| -values by taking the multiplicative inverse. The e-values proposed in this article are valid in finite samples without any assumptions on the data-generating processes. They also allow optional stopping, so a forecast user may decide to interrupt evaluation, taking into account the available data at any time, and still draw statistically valid inference, which is generally not true for classical |$p$| -value-based tests. In a case study on post-processing of precipitation forecasts, state-of-the-art forecast dominance tests and e-values lead to the same conclusions. [ABSTRACT FROM AUTHOR]

An important and often discussed research problem in statistics is how to compare several populations; examples arise in medical science, engineering, finance and other fields. Often population means or medians are compared. However, one population may have a higher mean income, for example, because of a small number of super-rich individuals; the mean therefore may not reflect the wealth of the general population. Instead, an index of the degree of stochastic dominance of one population over another would better reflect their relative wealth. Currently, we can estimate such an index under restrictive conditions, but there is no generic estimator with a known asymptotic distribution. In this paper, we suggest linking the populations via the density ratio model. Under this model, we develop an empirical likelihood estimator and establish its asymptotic normality. In addition, we improve the estimation efficiency by examining the similarities between the populations. Furthermore, we provide a valid bootstrap method for hypothesis testing and the construction of confidence intervals. Simulation experiments show that the proposed estimator substantially improves the estimation efficiency and power of the test, and leads to confidence intervals with satisfactorily precise coverage probabilities. It is also robust with respect to mild model misspecification. Two examples are given to demonstrate the usefulness of both the method and the concept. [ABSTRACT FROM AUTHOR]

Replicability analysis aims to identify the overlapping signals across independent studies that examine the same features. For this purpose we develop hypothesis testing procedures that first select the promising features from each of two studies separately. Only those features selected in both studies are then tested. The proposed procedures have theoretical guarantees regarding their control of the familywise error rate or false discovery rate on the replicability claims. They can also be used for signal discovery in each study separately, with the desired error control. Their power for detecting truly replicable findings is compared to alternatives. We illustrate the procedures on behavioural genetics data. [ABSTRACT FROM AUTHOR]

Combining p-values from independent statistical tests is a popular approach to meta-analysis, particularly when the data underlying the tests are either no longer available or are difficult to combine. Numerous p-value combination methods appear in the literature, each with different statistical properties, yet often the final choice used in a meta-analysis can seem arbitrary, as if all effort has been expended in building the models that gave rise to the p-values. Birnbaum (1954) showed that any reasonable p-value combiner must be optimal against some alternative hypothesis. Starting from this perspective and recasting each method of combining p-values as a likelihood ratio test, we present theoretical results for some standard combiners that provide guidance on how a powerful combiner might be chosen in practice. [ABSTRACT FROM AUTHOR]

Fisher randomization tests for Neyman's null hypothesis of no average treatment effect are considered in a finite-population setting associated with completely randomized experiments involving more than two treatments. The consequences of using the F statistic to conduct such a test are examined, and we argue that under treatment effect heterogeneity, use of the F statistic in the Fisher randomization test can severely inflate theType I error under Neyman's null hypothesis. We propose to use an alternative test statistic, derive its asymptotic distributions under Fisher's and Neyman's null hypotheses, and demonstrate its advantages through simulations. [ABSTRACT FROM AUTHOR]

Separability is a common simplifying assumption on the covariance structure of spatiotemporal functional data. We present three tests of separability, one a functional extension of the Monte Carlo likelihood method of Mitchell et al. (2006) and two based on quadratic forms. Our tests are based on asymptotic distributions of maximum likelihood estimators and do not require Monte Carlo simulation. The main theoretical contribution of this paper is the specification of the joint asymptotic distribution of these estimators, which can be used to derive many other tests. The main methodological finding is that one of the quadratic form methods, which we call a norm approach, emerges as a clear winner in terms of finite-sample performance in nearly every setting we considered. This approach focuses directly on the Frobenius distance between the spatiotemporal covariance function and its separable approximation. We demonstrate the efficacy of our methods via simulations and application to Irish wind data. [ABSTRACT FROM AUTHOR]

Several two-sample tests for high-dimensional data have been proposed recently, but they are powerful only against certain alternative hypotheses. In practice, since the true alternative hypothesis is unknown, it is unclear how to choose a powerful test. We propose an adaptive test that maintains high power across a wide range of situations and study its asymptotic properties. Its finite-sample performance is compared with that of existing tests. We apply it and other tests to detect possible associations between bipolar disease and a large number of single nucleotide polymorphisms on each chromosome based on data from a genome-wide association study. Numerical studies demonstrate the superior performance and high power of the proposed test across a wide spectrum of applications. [ABSTRACT FROM AUTHOR]

We address the problem of testing for a parametric function of fixed effects in mixed models. We propose a test based on the distance between two empirical error distribution functions, which are constructed from residuals calculated under the opposing hypotheses. The proposed test statistic has power against all alternatives, and its asymptotic distribution is derived. A simulation study shows that the test outperforms others in the literature. The test is applied to longitudinal data from an AIDS clinical trial and a growth study. [ABSTRACT FROM AUTHOR]

We consider large scale multiple testing for data that have locally clustered signals. With this structure, we apply techniques from changepoint analysis and propose a boundary detection algorithm so that the clustering information can be utilized. Consequently the precision of the multiple testing procedure is substantially improved. We study tests with independent as well as dependent p-values. Monte Carlo simulations suggest that the methods perform well with realistic sample sizes and show improved detection ability compared with competing methods. Our procedure is applied to a genome-wide association dataset of blood lipids. [ABSTRACT FROM AUTHOR]

A framework for classification is developed with a notion of confidence. In this framework, a classifier consists of two tolerance regions in the predictor space, with a specified coverage level for each class. The classifier also produces an ambiguous region where the classification needs further investigation. Theoretical analysis reveals interesting structures of the confidence-ambiguity trade-off, and the optimal solution is characterized by extending the Neyman–Pearson lemma. We provide general estimating procedures, along with rates of convergence, based on estimates of the conditional probabilities. The method can be easily implemented with good robustness, as illustrated through theory, simulation and a data example. [ABSTRACT FROM PUBLISHER]

In this paper we derive a new p-value based multiple testing procedure that improves upon the Hommel procedure by gaining power as well as having a simpler step-up structure similar to the Hochberg procedure. The key to this improvement is that the Hommel procedure can be improved by a consonant procedure. Exact critical constants of this new procedure can be numerically determined. The zeroth-order approximations to the exact critical constants, albeit slightly conservative, are simple to use and need no tabling, and hence are recommended in practice. The proposed procedure is shown to control the familywise error rate under independence among the p-values. Simulations empirically demonstrate familywise error rate control under positive and negative dependence. Power superiority of the proposed procedure over competing ones is also empirically demonstrated. Illustrative examples are given. [ABSTRACT FROM PUBLISHER]

The higher criticism test is effective for testing a joint null hypothesis against a sparse alternative, e.g., for testing the effect of a gene or genetic pathway that consists of d genetic markers. Accurate p-value calculations for the higher criticism test based on the asymptotic distribution require a very large d, which is not the case for the number of genetic variants in a gene or a pathway. In this paper we propose an analytical method for accurately computing the p-value of the higher criticism test for finite-d problems. Unlike previous treatments, this method does not rely on asymptotics in d or on simulation, and is exact for arbitrary d when the test statistics are normally distributed. The method is particularly computationally advantageous when d is not large. We illustrate the proposed method with a case-control genome-wide association study of lung cancer and compare its power with competing methods through simulations. [ABSTRACT FROM PUBLISHER]

When the multiple correlation coefficient is used to measure how strongly a given variable can be linearly associated with a set of covariates, it suffers from an upward bias that cannot be ignored in the presence of a moderately high dimensional covariate. Under an independent component model, we derive an asymptotic approximation to the distribution of the squared multiple correlation coefficient that depends on a simple correction factor. We show that this approximation enables us to construct reliable confidence intervals on the population coefficient even when the ratio of the dimension to the sample size is close to unity and the variables are non-Gaussian. [ABSTRACT FROM PUBLISHER]

The table of contents for Volume 101 of "Biometrika" is presented.