No Arabic abstract
When testing for replication of results from a primary study with two-sided hypotheses in a follow-up study, we are usually interested in discovering the features with discoveries in the same direction in the two studies. The direction of testing in the follow-up study for each feature can therefore be decided by the primary study. We prove that in this case the methods suggested in Heller, Bogomolov, and Benjamini (2014) for control over false replicability claims are valid. Specifically, we prove that if we input into the procedures in Heller, Bogomolov, and Benjamini (2014) the one-sided p-values in the directions favoured by the primary study, then we achieve directional control over the desired error measure (family-wise error rate or false discovery rate).
For a multivariate linear model, Wilks likelihood ratio test (LRT) constitutes one of the cornerstone tools. However, the computation of its quantiles under the null or the alternative requires complex analytic approximations and more importantly, these distributional approximations are feasible only for moderate dimension of the dependent variable, say $ple 20$. On the other hand, assuming that the data dimension $p$ as well as the number $q$ of regression variables are fixed while the sample size $n$ grows, several asymptotic approximations are proposed in the literature for Wilks $bLa$ including the widely used chi-square approximation. In this paper, we consider necessary modifications to Wilks test in a high-dimensional context, specifically assuming a high data dimension $p$ and a large sample size $n$. Based on recent random matrix theory, the correction we propose to Wilks test is asymptotically Gaussian under the null and simulations demonstrate that the corrected LRT has very satisfactory size and power, surely in the large $p$ and large $n$ context, but also for moderately large data dimensions like $p=30$ or $p=50$. As a byproduct, we give a reason explaining why the standard chi-square approximation fails for high-dimensional data. We also introduce a new procedure for the classical multiple sample significance test in MANOVA which is valid for high-dimensional data.
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 $pi_0$ of true null hypotheses. Randomized $p$-values have been proposed to remedy this issue. In the present work, we discuss the application of randomized $p$-values in replicability analysis. In particular, we introduce a general class of statistical models for which valid, randomized $p$-values can be calculated easily. By means of computer simulations, we demonstrate that their usage typically leads to a much more accurate estimation of $pi_0$. Finally, we apply our proposed methodology to a real data example from genomics.
Small study effects occur when smaller studies show different, often larger, treatment effects than large ones, which may threaten the validity of systematic reviews and meta-analyses. The most well-known reasons for small study effects include publication bias, outcome reporting bias and clinical heterogeneity. Methods to account for small study effects in univariate meta-analysis have been extensively studied. However, detecting small study effects in a multivariate meta-analysis setting remains an untouched research area. One of the complications is that different types of selection processes can be involved in the reporting of multivariate outcomes. For example, some studies may be completely unpublished while others may selectively report multiple outcomes. In this paper, we propose a score test as an overall test of small study effects in multivariate meta-analysis. Two detailed case studies are given to demonstrate the advantage of the proposed test over various naive applications of univariate tests in practice. Through simulation studies, the proposed test is found to retain nominal Type I error with considerable power in moderate sample size settings. Finally, we also evaluate the concordance between the proposed test with the naive application of univariate tests by evaluating 44 systematic reviews with multiple outcomes from the Cochrane Database.
Given a family of null hypotheses $H_{1},ldots,H_{s}$, we are interested in the hypothesis $H_{s}^{gamma}$ that at most $gamma-1$ of these null hypotheses are false. Assuming that the corresponding $p$-values are independent, we are investigating combined $p$-values that are valid for testing $H_{s}^{gamma}$. In various settings in which $H_{s}^{gamma}$ is false, we determine which combined $p$-value works well in which setting. Via simulations, we find that the Stouffer method works well if the null $p$-values are uniformly distributed and the signal strength is low, and the Fisher method works better if the null $p$-values are conservative, i.e. stochastically larger than the uniform distribution. The minimum method works well if the evidence for the rejection of $H_{s}^{gamma}$ is focused on only a few non-null $p$-values, especially if the null $p$-values are conservative. Methods that incorporate the combination of $e$-values work well if the null hypotheses $H_{1},ldots,H_{s}$ are simple.
HIV-1C is the most prevalent subtype of HIV-1 and accounts for over half of HIV-1 infections worldwide. Host genetic influence of HIV infection has been previously studied in HIV-1B, but little attention has been paid to the more prevalent subtype C. To understand the role of host genetics in HIV-1C disease progression, we perform a study to assess the association between longitudinally collected measures of disease and more than 100,000 genetic markers located on chromosome 6. The most common approach to analyzing longitudinal data in this context is linear mixed effects models, which may be overly simplistic in this case. On the other hand, existing non-parametric methods may suffer from low power due to high degrees of freedom (DF) and may be computationally infeasible at the large scale. We propose a functional principal variance component (FPVC) testing framework which captures the nonlinearity in the CD4 and viral load with potentially low DF and is fast enough to carry out thousands or millions of times. The FPVC testing unfolds in two stages. In the first stage, we summarize the markers of disease progression according to their major patterns of variation via functional principal components analysis (FPCA). In the second stage, we employ a simple working model and variance component testing to examine the association between the summaries of disease progression and a set of single nucleotide polymorphisms. We supplement this analysis with simulation results which indicate that FPVC testing can offer large power gains over the standard linear mixed effects model.