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.

Value at Risk (VaR) is a fundamental tool for managing market risks. It measures the worst loss to be expected of a portfolio over a given time horizon under normal market conditions at a given confidence level. Calculation of VaR frequently involves estimating the volatility of return processes and quantiles of standardized returns. In this paper, several semiparametric techniques are introduced to estimate the volatilities of the market prices of a portfolio. In addition, both parametric and nonparametric techniques are proposed to estimate the quantiles of standardized return processes. The newly proposed techniques also have the flexibility to adapt automatically to the changes in the dynamics of market prices over time. Their statistical efficiencies are studied both theoretically and empirically. The combination of newly proposed techniques for estimating volatility and standardized quantiles yields several new

Folded concave penalization methods have been shown to enjoy the strong oracle property for high-dimensional sparse estimation. However, a folded concave penalization problem usually has multiple local solutions and the oracle property is established only for one of the unknown local solutions. A challenging fundamental issue still remains that it is not clear whether the local optimum computed by a given optimization algorithm possesses those nice theoretical properties. To close this important theoretical gap in over a decade, we provide a unified theory to show explicitly how to obtain the oracle solution via the local linear approximation algorithm. For a folded concave penalized estimation problem, we show that as long as the problem is localizable and the oracle estimator is well behaved, we can obtain the oracle estimator by using the one-step local linear approximation. In addition, once the oracle estimator is obtained, the local linear approximation algorithm converges, namely, it produces the same estimator in the next iteration. The general theory is demonstrated by using four classical sparse estimation problems, that is, sparse linear regression, sparse logistic regression, sparse precision matrix estimation, and sparse quantile regression.

This paper studies a weighted local linear regression smoother for longitudinal/clustered data, which takes a form similar to the classical weighted least squares estimate. As a hybrid of the methods of Chen and Jin (2005) and Wang (2003), the proposed local linear smoother maintains the advantages of both methods in computational and theoretical simplicity, variance minimization and bias reduction. Moreover, the proposed smoother is optimal in the sense that it attains linear minimax efficiency when the within-cluster correlation is correctly specified. In the special case that the joint density of covariates in a cluster exists and is continuous, any working within-cluster correlation would lead to linear minimax efficiency for the proposed method.

Measuring conditional dependence is an important topic in statistics with broad applications including graphical models. Under a factor model setting, a new conditional dependence measure based on projection is proposed. The corresponding conditional independence test is developed with the asymptotic null distribution unveiled where the number of factors could be high-dimensional. It is also shown that the new test has control over the asymptotic significance level and can be calculated efficiently. A generic method for building dependency graphs without Gaussian assumption using the new test is elaborated. Numerical results and real data analysis show the superiority of the new method.