The purpose of this paper is to propose methodologies for statistical inference of low dimensional parameters with high dimensional data.We focus on constructing confidence intervals for individual coefficients and linear combinations of several of them in a linear regression model, although our ideas are applicable in a much broader context.The theoretical results that are presented provide sufficient conditions for the asymptotic normality of the proposed estimators along with a consistent estimator for their finite dimensional covariance matrices. These sufficient conditions allow the number of variables to exceed the sample size and the presence of many small non-zero coefficients. Our methods and theory apply to interval estimation of a preconceived regression coefficient or contrast as well as simultaneous interval estimation of many regression coefficients. Moreover, the method proposed turns the regression data into an approximate Gaussian sequence of point estimators of individual regression coefficients, which can be used to select variables after proper thresholding. The simulation results that are presented demonstrate the accuracy of the coverage probability of the confidence intervals proposed as well as other desirable properties, strongly supporting the theoretical results.

We demonstrate how path integrals often used in problems of theoretical physics can be adapted to provide a machinery for performing Bayesian inference in function spaces. Such inference comes about naturally in the study of inverse problems of recovering continuous (infinite dimensional) coefficient functions from ordinary or partial differential equations, a problem which is typically ill-posed. Regularization of these problems using L2 function spaces (Tikhonov regularization) is equivalent to Bayesian probabilistic inference, using a Gaussian prior. The Bayesian interpretation of inverse problem regularization is useful since it allows one to quantify and characterize error and degree of precision in the solution of inverse problems, as well as examine assumptions made in solving the problem—namely whether the subjective choice of regularization is compatible with prior knowledge. Using path-integral formalism, Bayesian inference can be explored through various perturbative techniques, such as the semiclassical approximation, which we use in this manuscript. Perturbative path-integral approaches, while offering alternatives to computational approaches like Markov-Chain-Monte-Carlo (MCMC), also provide natural starting points for MCMC methods that can be used to refine approximations. In this manuscript, we illustrate a path-integral formulation for inverse problems and demonstrate it on an inverse problem in membrane biophysics as well as inverse problems in potential theories involving the Poisson equation.

We provide here a framework to analyze the phase transition phenomenon of slice inverse regression (SIR), a supervised dimension reduction technique introduced by \cite{Li:1991}. Under mild conditions, the asymptotic ratio ρ=limp/n is the phase transition parameter and the SIR estimator is consistent if and only if ρ=0. When dimension p is greater than n, we propose a diagonal thresholding screening SIR (DT-SIR) algorithm. This method provides us with an estimate of the eigen-space of the covariance matrix of the conditional expectation var(E[x|y]). The desired dimension reduction space is then obtained by multiplying the inverse of the covariance matrix on the eigen-space. Under certain sparsity assumptions on both the covariance matrix of predictors and the loadings of the directions, we prove the consistency of DT-SIR in estimating the dimension reduction space in high dimensional data analysis. Extensive numerical experiments demonstrate superior performances of the proposed method in comparison to its competitors.

Due to vast sequence divergence among different viral groups, sequence alignment is not directly applicable to genome-wide comparative analysis of viruses. More and more attention has been paid to alignment-free methods for whole genome comparison and phylogenetic tree reconstruction. Among alignment-free methods, the recently proposed ‘‘Natural Vector (NV) representation” has successfully been used to study the phylogeny of multi-segmented viruses based on a 12-dimensional genome space derived from the nucleotide sequence structure. But the preference of proteomes over genomes for the determination of viral phylogeny was not deeply investigated. As the translated products of genes, proteins directly form the shape of viral structure and are vital for all metabolic pathways. In this study, using the NV representation of a protein sequence along with the Hausdorff distance suitable to compare point sets, we construct a 60-dimensional protein space to analyze the evolutionary relationships of 4021 viruses by whole-proteomes in the current NCBI Reference Sequence Database (RefSeq). We also take advantage of the previously developed natural graphical representation to recover viral phylogeny. Our results demonstrate that the proposed method is efficient and accurate for classifying viruses. The accuracy rates of our predictions such as for Baltimore II viruses are as high as 95.9% for family labels, 95.7% for subfamily labels and 96.5% for genus labels. Finally, we discover that proteomes lead to better viral classification when reliable protein sequences are abundant. In other cases, the accuracy rates using proteomes are still comparable to that of genomes.

In this paper we introduce a smooth version of local linear regression estimators and address their advantages. The MSE and MISE of the estimators are computed explicitly. It turns out that the local linear regression smoothers have nice sampling properties and high minimax efficiency-they are not only efficient in rates but also nearly efficient in constant factors. In the nonparametric regression context, the asymptotic minimax lower bound is developed via the heuristic of the" hardest onedimensional subproblem" of Donoho and Liu. Connections of the minimax risk with the modulus of continuity are made. The lower bound is also applicable for estimating conditional mean (regression) and conditional quantiles for both fixed and random design regression problems.

Frequentists' inference often delivers point estimators associated with condence intervals or sets for parameters of interest. Constructing the condence intervals or sets requires understanding the sampling distributions of the point estimators, which, in many but not all cases, are related to asymptotic Normal distributions ensured by central limit theorems. Although previous literature has established various forms of central limit theorems for statistical inference in super population models, we still need general and convenient forms of central limit theorems for some randomization-based causal analysis of experimental data, where the parameters of interests are functions of a nite population and randomness comes solely from the treatment assignment. We use central limit theorems for sample surveys and rank statistics to establish general forms of the nite population central limit theorems that are particularly useful for proving asymptotic distributions of randomization tests under the sharp null hypothesis of zero individual causal eects, and for obtaining the asymptotic repeated sampling distributions of the causal eect estimators. The new central limit theorems hold for general experimental designs with multiple treatment levels, multiple treatment factors and vector outcomes, and are immediately applicable for studying the asymptotic properties of many methods in causal inference, including instrumental variable, regression adjustment, rerandomization, clustered randomized experiments, and so on. Previously, the asymptotic properties of these problems are often based on heuristic arguments, which in fact rely on general forms of nite population central limit theorems that have not been established before. Our new theorems ll in this gap by providing more solid theoretical foundation for asymptotic randomization-based causal inference.

For multiple index models, it has recently been shown that the sliced inverse regression (SIR) is consistent for estimating the sufficient dimension reduction (SDR) subspace if and only if the dimension p and sample size n satisfies that ρ=limp/n=0. Thus, when p is of the same or a higher order of n, additional assumptions such as sparsity have to be imposed in order to ensure consistency for SIR. By constructing artificial response variables made up from top eigenvectors of the estimated conditional covariance matrix, \widehat{var(𝔼[x|y])}, we introduce a simple Lasso regression method to obtain an estimate of the SDR subspace. The resulting algorithm, Lasso-SIR, is shown to be consistent and achieve the optimal convergence rate under certain sparsity conditions when p is of order o(n^2λ^2) where λ is the generalized signal noise ratio. We also demonstrate the superior performance of Lasso-SIR compared with existing approaches via extensive numerical studies and several real data examples.

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Comparing DNA or protein sequences plays an important role in the functional analysis of genomes. Despite many methods available for sequences comparison, few methods retain the information content of sequences. We propose a new approach, the Yau-Hausdorff method, which considers all translations and rotations when seeking the best match of graphical curves of DNA or protein sequences. The complexity of this method is lower than that of any other two dimensional minimum Hausdorff algorithm. The Yau-Hausdorff method can be used for measuring the similarity of DNA sequences based on two important tools: the Yau-Hausdorff distance and graphical representation of DNA sequences. The graphical representations of DNA sequences conserve all sequence information and the Yau-Hausdorff distance is mathematically proved as a true metric. Therefore, the proposed distance can preciously measure the similarity of DNA sequences. The phylogenetic analyses of DNA sequences by the Yau-Hausdorff distance show the accuracy and stability of our approach in similarity comparison of DNA or protein sequences. This study demonstrates that Yau-Hausdorff distance is a natural metric for DNA and protein sequences with high level of stability. The approach can be also applied to similarity analysis of protein sequences by graphic representations, as well as general two dimensional shape matching.

A decisive question in nonparametric smoothing techniques is the choice of the bandwidth or smoothing parameter. The present paper addresses this question when using local polynomial approximations for estimating the regression function and its derivatives. A fully-automatic bandwidth selection procedure has been proposed by Fan and Gijbels (1995a), and the empirical performance of it was tested in detail via a variety of examples. Those experiences supported the methodology towards a great extend. In this paper we establish asymptotic results for the proposed variable bandwidth selector. We provide the rate of convergence of the bandwidth estimate, and obtain the asymptotic distribution of its error relative to the theoretical optimal variable bandwidth. These asymptotic properties give extra support to the proposed bandwidth selection procedure. It is also demonstrated how the proposed selection