<b></b> Estimation of the covariance structure of longitudinal processes is a fundamental prerequisite for the practical deployment of functional mapping designed to study the genetic regulation and network of quantitative variation in dynamic complex traits. We present a nonparametric approach for estimating the covariance structure of a quantitative trait measured repeatedly at a series of time points. Specifically, we adopt Huang et al.'s (2006,<i>Biometrika</i><b>93</b>, 8598) approach of invoking the modified Cholesky decomposition and converting the problem into modeling a sequence of regressions of responses. A regularized covariance estimator is obtained using a normal penalized likelihood with an<i>L</i>₂ penalty. This approach, embedded within a mixture likelihood framework, leads to enhanced accuracy, precision, and flexibility of functional mapping while preserving its biological relevance. Simulation studies are

This paper discusses statistical methods for estimating complex correlation structure from large pharmacogenomic datasets. We selectively review several prominent statistical methods for estimating large covariance matrix for understanding correlation structure, inverse covariance matrix for network modeling, large-scale simultaneous tests for selecting significantly differently expressed genes and proteins and genetic markers for complex diseases, and high dimensional variable selection for identifying important molecules for understanding molecule mechanisms in pharmacogenomics. Their applications to gene network estimation and biomarker selection are used to illustrate the methodological power. Several new challenges of Big data analysis, including complex data distribution, missing data, measurement error, spurious correlation, endogeneity, and the need for robust statistical methods, are also discussed.

For the data based choice of the bandwidth of a kernel density estimator, several methods have recently been proposed which have a very fast asymptotic rate of convergence to the optimal bandwidth. In particular the relative rate of convergence is the square root of the sample size, which is known to be the best possible. The point of this paper is to show how semiparametric arguments can be employed to calculate the best possible constant coefficient, that is, an analog of the usual Fisher information, in this convergence. This establishes an important benchmark as to how well bandwidth selection methods can ever hope to perform. It is seen that some existing methods attain the bound, others do not.

Motivated by recent work on studying massive imaging data in various neuroimaging studies, we propose a novel spatially varying coefficient model (SVCM) to capture the varying association between imaging measures in a three-dimensional volume (or two-dimensional surface) with a set of covariates. Two stylized features of neuorimaging data are the presence of multiple piecewise smooth regions with unknown edges and jumps and substantial spatial correlations. To specifically account for these two features, SVCM includes a measurement model with multiple varying coefficient functions, a jumping surface model for each varying coefficient function, and a functional principal component model. We develop a three-stage estimation procedure to simultaneously estimate the varying coefficient functions and the spatial correlations. The estimation procedure includes a fast multiscale adaptive estimation and

We derive the asymptotic distributions of the spiked eigenvalues and eigenvectors under a generalized and unified asymptotic regime, which takes into account the magnitude of spiked eigenvalues, sample size, and dimensionality. This regime allows high dimensionality and diverging eigenvalues and provides new insights into the roles that the leading eigenvalues, sample size, and dimensionality play in principal component analysis. Our results are a natural extension of those in Paul (2007) to a more general setting and solve the rates of convergence problems in Shen et al.(2013). They also reveal the biases of estimating leading eigenvalues and eigenvectors by using principal component analysis, and lead to a new covariance estimator for the approximate factor model, called shrinkage principal orthogonal complement thresholding (S-POET), that corrects the biases. Our results are successfully applied to