In an empirical Bayesian setting, we provide a new multiple testing method, useful when an additional covariate is available, that influences the probability of each null hypothesis being true. We measure the posterior significance of each test conditionally on the covariate and the data, leading to greater power. Using covariate-based prior information in an unsupervised fashion, we produce a list of significant hypotheses which differs in length and order from the list obtained by methods not taking covariate-information into account. Covariate-modulated posterior probabilities of each null hypothesis are estimated using a fast approximate algorithm. The new method is applied to expression quantitative trait loci (eQTL) data.
An important feature of linear mixed models and generalized linear mixed models is that the conditional mean of the response given the random effects, after transformed by a link function, is linearly related to the fixed covariate effects and random effects. Therefore, it is of practical importance to test the adequacy of this assumption, particularly the assumption of linear covariate effects. In this paper, we review procedures that can be used for testing polynomial covariate effects in these popular models. Specifically, four types of hypothesis testing approaches are reviewed, i.e. R tes…
Matrix-covariate is now frequently encountered in many biomedical researches. It is common to fit conventional statistical models by vectorizing matrix-covariate. This strategy, however, results in a large number of parameters, while the available sample size is relatively too small to have reliable analysis results. To overcome the problem of high-dimensionality in hypothesis testing, variance component test has been proposed with promise detection power, but is not straightforward to provide estimates of effect size. In this work, we overcome the problem of high-dimensionality by utilizing t…
In this paper, we study a generalization of the two-groups model in the presence of covariates --- a problem that has recently received much attention in the statistical literature due to its applicability in multiple hypotheses testing problems. The model we consider allows for infinite dimensional parameters and offers flexibility in modeling the dependence of the response on the covariates. We discuss the identifiability issues arising in this model and systematically study several estimation strategies. We propose a tuning parameter-free nonparametric maximum likelihood method, implementab…
Sepsis is a major cause of mortality in the intensive care units (ICUs). Early intervention of sepsis can improve clinical outcomes for sepsis patients. Machine learning models have been developed for clinical recognition of sepsis. A common assumption of supervised machine learning models is that the covariates in the testing data follow the same distributions as those in the training data. When this assumption is violated (e.g., there is covariate shift), models that performed well for training data could perform badly for testing data. Covariate shift happens when the relationships between …
Although there is a rapidly growing literature on dynamic connectivity methods, the primary focus has been on separate network estimation for each individual, which fails to leverage common patterns of information. We propose novel graph-theoretic approaches for estimating a population of dynamic networks that are able to borrow information across multiple heterogeneous samples in an unsupervised manner and guided by covariate information. Specifically, we develop a Bayesian product mixture model that imposes independent mixture priors at each time scan and uses covariates to model the mixture…
The analysis of high dimensional survival data is challenging, primarily due to the problem of overfitting which occurs when spurious relationships are inferred from data that subsequently fail to exist in test data. Here we propose a novel method of extracting a low dimensional representation of covariates in survival data by combining the popular Gaussian Process Latent Variable Model (GPLVM) with a Weibull Proportional Hazards Model (WPHM). The combined model offers a flexible non-linear probabilistic method of detecting and extracting any intrinsic low dimensional structure from high dimen…
This paper aims to improve the explainability of Autoencoder's (AE) predictions by proposing two explanation methods based on the mean and epistemic uncertainty of log-likelihood estimate, which naturally arise from the probabilistic formulation of the AE called Bayesian Autoencoders (BAE). To quantitatively evaluate the performance of explanation methods, we test them in sensor network applications, and propose three metrics based on covariate shift of sensors : (1) G-mean of Spearman drift coefficients, (2) G-mean of sensitivity-specificity of explanation ranking and (3) sensor explanation q…
Modelling the first-order intensity function is one of the main aims in point process theory, and it has been approached so far from different perspectives. One appealing model describes the intensity as a function of a spatial covariate. In the recent literature, estimation theory and several applications have been developed assuming this model, but without formally checking this assumption. In this paper we address this problem for a non-homogeneous Poisson point process, by proposing a new test based on an $L^2$-distance. We also prove the asymptotic normality of the statistic and we sugges…
As a crucial problem in statistics is to decide whether additional variables are needed in a regression model. We propose a new multivariate test to investigate the conditional mean independence of Y given X conditioning on some known effect Z, i.e., E(Y|X, Z) = E(Y|Z). Assuming that E(Y|Z) and Z are linearly related, we reformulate an equivalent notion of conditional mean independence through transformation, which is approximated in practice. We apply the martingale difference divergence (Shao and Zhang, 2014) to measure conditional mean dependence, and show that the estimation error from app…
Hierarchical inference in (generalized) regression problems is powerful for finding significant groups or even single covariates, especially in high-dimensional settings where identifiability of the entire regression parameter vector may be ill-posed. The general method proceeds in a fully data-driven and adaptive way from large to small groups or singletons of covariates, depending on the signal strength and the correlation structure of the design matrix. We propose a novel hierarchical multiple testing adjustment that can be used in combination with any significance test for a group of covar…
We propose a novel method for testing the null hypothesis of no effect of a covariate on the response in the context of functional linear concurrent regression. We establish an equivalent random effects formulation of our functional regression model under which our testing problem reduces to testing for zero variance component for random effects. For this purpose, we use a one-sided score test approach, which is an extension of the classical score test. We provide theoretical justification as to why our testing procedure has the right levels (asymptotically) under null using standard assumptio…
Recently Khmaladze has shown how to `rotate' one empirical process to another. This paper is the first to apply this transform when successive data points are generated by a single distributional family, but with covariates varying over the sample. The application is to Bernoulli trials, and new results show how group sizes rotated are related to the number of parameters, and explore the impact of different types of data generating processes. The utility of the rotation is clear: goodness of fit tests after rotation to a distribution free process are easily computed, show excellent convergence…
With the development of next generation sequencing technology, researchers have now been able to study the microbiome composition using direct sequencing, whose output are bacterial taxa counts for each microbiome sample. One goal of microbiome study is to associate the microbiome composition with environmental covariates. We propose to model the taxa counts using a Dirichlet-multinomial (DM) regression model in order to account for overdispersion of observed counts. The DM regression model can be used for testing the association between taxa composition and covariates using the likelihood rat…
University of Southern California（南加州大学）；Princeton University（普林斯顿大学）
Hypothesis testing in the linear regression model is a fundamental statistical problem. We consider linear regression in the high-dimensional regime where the number of parameters exceeds the number of samples ($p> n$). In order to make informative inference, we assume that the model is approximately sparse, that is the effect of covariates on the response can be well approximated by conditioning on a relatively small number of covariates whose identities are unknown. We develop a framework for testing very general hypotheses regarding the model parameters. Our framework encompasses testing wh…
Identifying disease-associated changes in DNA methylation can help to gain a better understanding of disease etiology. Bisulfite sequencing technology allows the generation of methylation profiles at single base of DNA. We previously developed a method for estimating smooth covariate effects and identifying differentially methylated regions (DMRs) from bisulfite sequencing data, which copes with experimental errors and variable read depths; this method utilizes the binomial distribution to characterize the variability in the methylated counts. However, bisulfite sequencing data frequently incl…
Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of common statistical approaches to detect treatment differences, potentially hampering the regulatory approval of safe and efficacious therapies. A novel solution to this problem is proposed. A list of baseline covariates that have the potential to be prognostic for survival under either treatment is pre-specified in the analysis plan. At the analysis stage, u…
The R package CVEK introduces a suite of flexible machine learning models and robust hypothesis tests for learning the joint nonlinear effects of multiple covariates in limited samples. It implements the Cross-validated Ensemble of Kernels (CVEK)(Liu and Coull 2017), an ensemble-based kernel machine learning method that adaptively learns the joint nonlinear effect of multiple covariates from data, and provides powerful hypothesis tests for both main effects of features and interactions among features. The R Package CVEK provides a flexible, easy-to-use implementation of CVEK, and offers a wide…
Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial patients given access to novel treatments. However, due to lack of randomization, RCT patients and external controls may differ with respect to covariates that may or may not have been measured. Hence, after controlling for measured covariates, for instance by matching, testing for treatment effect using external controls may still be subject to unmeasured bi…
