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 deconvolution in R^d, d≥1, with mixing density p(∈\mathscr{P}) and kernel h, the mixture density f_p(∈\mathscr{F}_p) is estimated with MDE f_{\hat{p}n}, having upper L1-error rate, an, in probability or in risk; \hat{p}_n∈\mathscr{P}. In one application, \mathscr{P} consists of L1-separable densities in R with differences changing sign at most J times and h(x−y) Totally Positive. When h is known and p is \tilde{q}-smooth, vanishing outside a compact in R^d, plug-in upper bounds are provided for the L2-error rate of \hat{p}_n and its [s]-th mixed partial derivative \hat{p}^{(s)}_n, via ∥f_{\hat{p}_n}−f_p∥_1, with rates (log a^{−1}_n)^{−N_1} and a^{N_2}_n, respectively, for h super-smooth and smooth; \tilde{q}∈R^+, [s] ≤ \tilde{q}, d≥1, N_1>0, N_2>0. For a_n ∼ (logn)^ζ⋅(n^{−δ}), the former rate is optimal for any δ>0 and the latter misses the optimal by the factor (logn)^ξ when δ=.5; ζ>0, ξ>0. N_1 and N_2 appear in optimal rates and lower error and risk bounds in the deconvolution literature.

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.

Many statistical models seek relationship between variables via subspaces of reduced dimensions. For instance, in factor models, variables are roughly distributed around a low dimensional subspace determined by the loading matrix; in mixed linear regression models, the coefficient vectors for different mixtures form a subspace that captures all regression functions; in multiple index models, the effect of covariates is summarized by the effective dimension reduction space.

Double-blind randomized controlled trials are traditionally seen as the gold standard for causal inferences as the difference-in-means estimator is an unbiased estimator of the average treatment effect in the experiment. The fact that this estimator is unbiased over all possible randomizations does not, however, mean that any given estimate is close to the true treatment effect. Similarly, while predetermined covariates will be balanced between treatment and control groups on average, large imbalances may be observed in a given experiment and the researcher may therefore want to condition on such covariates using linear regression. This article studies the theoretical properties of both the difference-in-means and OLS estimators conditional on observed differences in covariates. By deriving the statistical properties of the conditional estimators, we can establish guidance for how to deal with covariate imbalances.