In this paper, we propose a shrinkage framework for jointly estimating multiple covariance matrices by shrinking the sample covariance matrices towards the pooled sample covariance matrix. This framework allows us to borrow information across different groups. We derive the optimal shrinkage parameters under the Stein and quadratic loss functions, and prove that our derived estimators are asymptotically optimal when the sample size or the number of groups tends to infinity. Simulation studies demonstrate that our proposed shrinkage method performs favorably compared to the existing methods.

The determinant of the covariance matrix for high-dimensional data plays an important role in statistical inference and decision. It has many real applications including statistical tests and information theory. Due to the statistical and computational challenges with high dimensionality, little work has been proposed in the literature for estimating the determinant of high-dimensional covariance matrix. In this paper, we estimate the determinant of the covariance matrix using some recent proposals for estimating high-dimensional covariance matrix. Specifically, we consider a total of eight covariance matrix estimation methods for comparison. Through extensive simulation studies, we explore and summarize some interesting comparison results among all compared methods. We also provide practical guidelines based on the sample size, the dimension, and the correlation of the data set for estimating the determinant of high-dimensional covariance matrix. Finally, from a perspective of the loss function, the comparison study in this paper may also serve as a proxy to assess the performance of the covariance matrix estimation.

RNA-sequencing (RNA-Seq) has become a powerful technology to characterize gene expression profiles because it is more accurate and comprehensive than microarrays. Although statistical methods that have been developed for microarray data can be applied to RNA-Seq data, they are not ideal due to the discrete nature of RNA-Seq data. The Poisson distribution and negative binomial distribution are commonly used to model count data. Recently, Witten (2011) proposed a Poisson linear discriminant analysis for RNA-Seq data. The Poisson assumption may not be as appropriate as negative binomial distribution when biological replicates are available and in the presence of overdispersion (i.e., when the variance is larger than the mean). However, it is more complicated to model negative binomial variables because they involve a dispersion parameter that needs to be estimated. In this paper, we propose a negative binomial linear discriminant analysis for RNA-Seq data. By Bayes' rule, we construct the classifier by fitting a negative binomial model, and propose some plug-in rules to estimate the unknown parameters in the classifier. The relationship between the negative binomial classifier and the Poisson classifier is explored, with a numerical investigation of the impact of dispersion on the discriminant score. Simulation results show the superiority of our proposed method. We also analyze four real RNA-Seq data sets to demonstrate the advantage of our method in real-world applications.

High-throughput expression profiling techniques bring novel tools and also statistical challenges to genetic research. In addition to detecting differentially expressed genes, testing the significance of gene sets or pathway analysis has been recognized as an equally important problem. Owing to the "large p small n" paradigm, the traditional Hotelling's T2 test suffers from the singularity problem and therefore is not valid in this setting. In this paper, we propose a shrinkage-based diagonal Hotelling's test for both one-sample and two-sample cases. We also suggest several different ways to derive the approximate null distribution under different scenarios of p and n for our proposed shrinkage-based test. Simulation studies show that the proposed method performs comparably to existing competitors when n is moderate or large, but it is better when n is small. In addition, we analyze four gene expression data sets and they demonstrate the advantage of our proposed shrinkage-based diagonal Hotelling's test.

In this paper, we propose simultaneous confidence bands for the nonparametric link function in single-index models in the presence of a nuisance index parameter. We establish the asymptotic properties for the link function and its derivative that allow simultaneous confidence bands for various inference tasks. In addition, we propose an adaptive Neyman test statistic for testing the linearity of the link function. We then conduct simulation studies to evaluate the performance of the proposed method, and apply them to two data sets for illustration.