arXiv subjects

Hongzhe Li

Publications and source records attributed to Hongzhe Li.

At least 55 records · Page 3Linked to original sources

arXiv2020

Transfer Learning in Large-scale Gaussian Graphical Models with False Discovery Rate Control

Transfer learning for high-dimensional Gaussian graphical models (GGMs) is studied with the goal of estimating the target GGM by utilizing the data from similar and related auxiliary studies. The similarity between the target graph and each auxiliary graph is characterized by the sparsity of a divergence matrix. An estimation algorithm, Trans-CLIME, is proposed and shown to attain a faster convergence rate than the minimax rate in the single study setting. Furthermore, a debiased Trans-CLIME estimator is introduced and shown to be element-wise asymptotically normal. It is used to construct a multiple testing procedure for edge detection with false discovery rate control. The proposed estimation and multiple testing procedures demonstrate superior numerical performance in simulations and are applied to infer the gene networks in a target brain tissue by leveraging the gene expressions from multiple other brain tissues. A significant decrease in prediction errors and a significant increase in power for link detection are observed.

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arXiv2020

Optimal Estimation of Simultaneous Signals Using Absolute Inner Product with Applications to Integrative Genomics

Integrating the summary statistics from genome-wide association study (\textsc{gwas}) and expression quantitative trait loci (e\textsc{qtl}) data provides a powerful way of identifying the genes whose expression levels are potentially associated with complex diseases. A parameter called $T$-score that quantifies the genetic overlap between a gene and the disease phenotype based on the summary statistics is introduced based on the mean values of two Gaussian sequences. Specifically, given two independent samples $\mathbf{x}_n\sim N(θ, Σ_1)$ and $\mathbf{y}_n\sim N(μ, Σ_2)$, the $T$-score is defined as $\sum_{i=1}^n |θ_iμ_i|$, a non-smooth functional, which characterizes the amount of shared signals between two absolute normal mean vectors $|θ|$ and $|μ|$. Using approximation theory, estimators are constructed and shown to be minimax rate-optimal and adaptive over various parameter spaces. Simulation studies demonstrate the superiority of the proposed estimators over existing methods. The method is applied to an integrative analysis of heart failure genomics datasets and we identify several genes and biological pathways that are potentially causal to human heart failure.

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arXiv2020

Optimal Estimation of Bacterial Growth Rates Based on Permuted Monotone Matrix

Motivated by the problem of estimating the bacterial growth rates for genome assemblies from shotgun metagenomic data, we consider the permuted monotone matrix model $Y=ΘΠ+Z$, where $Y\in \mathbb{R}^{n\times p}$ is observed, $Θ\in \mathbb{R}^{n\times p}$ is an unknown approximately rank-one signal matrix with monotone rows, $Π\in \mathbb{R}^{p\times p}$ is an unknown permutation matrix, and $Z\in \mathbb{R}^{n\times p}$ is the noise matrix. This paper studies the estimation of the extreme values associated to the signal matrix $Θ$, including its first and last columns, as well as their difference. Treating these estimation problems as compound decision problems, minimax rate-optimal estimators are constructed using the spectral column sorting method. Numerical experiments through simulated and synthetic microbiome metagenomic data are presented, showing the superiority of the proposed methods over the alternatives. The methods are illustrated by comparing the growth rates of gut bacteria between inflammatory bowel disease patients and normal controls.

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arXiv2020

Optimal Permutation Recovery in Permuted Monotone Matrix Model

Motivated by recent research on quantifying bacterial growth dynamics based on genome assemblies, we consider a permuted monotone matrix model $Y=ΘΠ+Z$, where the rows represent different samples, the columns represent contigs in genome assemblies and the elements represent log-read counts after preprocessing steps and Guanine-Cytosine (GC) adjustment. In this model, $Θ$ is an unknown mean matrix with monotone entries for each row, $Π$ is a permutation matrix that permutes the columns of $Θ$, and $Z$ is a noise matrix. This paper studies the problem of estimation/recovery of $Π$ given the observed noisy matrix $Y$. We propose an estimator based on the best linear projection, which is shown to be minimax rate-optimal for both exact recovery, as measured by the 0-1 loss, and partial recovery, as quantified by the normalized Kendall's tau distance. Simulation studies demonstrate the superior empirical performance of the proposed estimator over alternative methods. We demonstrate the methods using a synthetic metagenomics dataset of 45 closely related bacterial species and a real metagenomic dataset to compare the bacterial growth dynamics between the responders and the non-responders of the IBD patients after 8 weeks of treatment.

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arXiv2020

Transfer Learning for High-dimensional Linear Regression: Prediction, Estimation, and Minimax Optimality

This paper considers the estimation and prediction of a high-dimensional linear regression in the setting of transfer learning, using samples from the target model as well as auxiliary samples from different but possibly related regression models. When the set of "informative" auxiliary samples is known, an estimator and a predictor are proposed and their optimality is established. The optimal rates of convergence for prediction and estimation are faster than the corresponding rates without using the auxiliary samples. This implies that knowledge from the informative auxiliary samples can be transferred to improve the learning performance of the target problem. In the case that the set of informative auxiliary samples is unknown, we propose a data-driven procedure for transfer learning, called Trans-Lasso, and reveal its robustness to non-informative auxiliary samples and its efficiency in knowledge transfer. The proposed procedures are demonstrated in numerical studies and are applied to a dataset concerning the associations among gene expressions. It is shown that Trans-Lasso leads to improved performance in gene expression prediction in a target tissue by incorporating the data from multiple different tissues as auxiliary samples.

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arXiv2019

High Dimensional M-Estimation with Missing Outcomes: A Semi-Parametric Framework

We consider high dimensional $M$-estimation in settings where the response $Y$ is possibly missing at random and the covariates $\mathbf{X} \in \mathbb{R}^p$ can be high dimensional compared to the sample size $n$. The parameter of interest $\boldsymbolθ_0 \in \mathbb{R}^d$ is defined as the minimizer of the risk of a convex loss, under a fully non-parametric model, and $\boldsymbolθ_0$ itself is high dimensional which is a key distinction from existing works. Standard high dimensional regression and series estimation with possibly misspecified models and missing $Y$ are included as special cases, as well as their counterparts in causal inference using 'potential outcomes'. Assuming $\boldsymbolθ_0$ is $s$-sparse ($s \ll n$), we propose an $L_1$-regularized debiased and doubly robust (DDR) estimator of $\boldsymbolθ_0$ based on a high dimensional adaptation of the traditional double robust (DR) estimator's construction. Under mild tail assumptions and arbitrarily chosen (working) models for the propensity score (PS) and the outcome regression (OR) estimators, satisfying only some high-level conditions, we establish finite sample performance bounds for the DDR estimator showing its (optimal) $L_2$ error rate to be $\sqrt{s (\log d)/ n}$ when both models are correct, and its consistency and DR properties when only one of them is correct. Further, when both the models are correct, we propose a desparsified version of our DDR estimator that satisfies an asymptotic linear expansion and facilitates inference on low dimensional components of $\boldsymbolθ_0$. Finally, we discuss various of choices of high dimensional parametric/semi-parametric working models for the PS and OR estimators. All results are validated via detailed simulations.

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arXiv2019

Hypothesis Testing in High-Dimensional Instrumental Variables Regression with an Application to Genomics Data

Gene expression and phenotype association can be affected by potential unmeasured confounders from multiple sources, leading to biased estimates of the associations. Since genetic variants largely explain gene expression variations, they can be used as instruments in studying the association between gene expressions and phenotype in the framework of high dimensional instrumental variable (IV) regression. However, because the dimensions of both genetic variants and gene expressions are often larger than the sample size, statistical inferences such as hypothesis testing for such high dimensional IV models are not trivial and have not been investigated in literature. The problem is more challenging since the instrumental variables (e.g., genetic variants) have to be selected among a large set of genetic variants. This paper considers the problem of hypothesis testing for sparse IV regression models and presents methods for testing single regression coefficient and multiple testing of multiple coefficients, where the test statistic for each single coefficient is constructed based on an inverse regression. A multiple testing procedure is developed for selecting variables and is shown to control the false discovery rate. Simulations are conducted to evaluate the performance of our proposed methods. These methods are illustrated by an analysis of a yeast dataset in order to identify genes that are associated with growth in the presence of hydrogen peroxide.

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arXiv2019

IFAA: Robust association identification and Inference For Absolute Abundance in microbiome analyses

The target of inference in microbiome analyses is usually relative abundance (RA) because RA in a sample (e.g., stool) can be considered as an approximation of RA in an entire ecosystem (e.g., gut). However, inference on RA suffers from the fact that RA are calculated by dividing absolute abundances (AA) over the common denominator (CD), the summation of all AA (i.e., library size). Because of that, perturbation in one taxon will result in a change in the CD and thus cause false changes in RA of all other taxa, and those false changes could lead to false positive/negative findings. We propose a novel analysis approach (IFAA) to make robust inference on AA of an ecosystem that can circumvent the issues induced by the CD problem and compositional structure of RA. IFAA can also address the confounding effect of library size and handle zero-inflated data structures. IFAA identifies microbial taxa associated with the covariates in Phase one and estimates the association parameters by employing an independent reference taxon in Phase two. Two real data applications are presented and extensive simulations show that IFAA outperforms other established existing approaches by a big margin in the presence of confounding effect of library size.

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arXiv2019

Multi-sample Estimation of Bacterial Composition Matrix in Metagenomics Data

Metagenomics sequencing is routinely applied to quantify bacterial abundances in microbiome studies, where the bacterial composition is estimated based on the sequencing read counts. Due to limited sequencing depth and DNA dropouts, many rare bacterial taxa might not be captured in the final sequencing reads, which results in many zero counts. Naive composition estimation using count normalization leads to many zero proportions, which tend to result in inaccurate estimates of bacterial abundance and diversity. This paper takes a multi-sample approach to the estimation of bacterial abundances in order to borrow information across samples and across species. Empirical results from real data sets suggest that the composition matrix over multiple samples is approximately low rank, which motivates a regularized maximum likelihood estimation with a nuclear norm penalty. An efficient optimization algorithm using the generalized accelerated proximal gradient and Euclidean projection onto simplex space is developed. The theoretical upper bounds and the minimax lower bounds of the estimation errors, measured by the Kullback-Leibler divergence and the Frobenius norm, are established. Simulation studies demonstrate that the proposed estimator outperforms the naive estimators. The method is applied to an analysis of a human gut microbiome dataset.

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arXiv2018

Two-sample Test of Community Memberships of Weighted Stochastic Block Models

Suppose two networks are observed for the same set of nodes, where each network is assumed to be generated from a weighted stochastic block model. This paper considers the problem of testing whether the community memberships of the two networks are the same. A test statistic based on singular subspace distance is developed. Under the weighted stochastic block models with dense graphs, the limiting distribution of the proposed test statistic is developed. Simulation results show that the test has correct empirical type 1 errors under the dense graphs. The test also behaves as expected in empirical power, showing gradual changes when the intra-block and inter-block distributions are close and achieving 1 when the two distributions are not so close, where the closeness of the two distributions is characterized by Renyi divergence of order 1/2. The Enron email networks are used to demonstrate the proposed test.

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arXiv2018

Conditional regression based on a multivariate zero-inflated logistic normal model for microbiome relative abundance data

The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive numbers of zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We propose a multivariate two-part zero-inflated logistic normal (MZILN) model to analyze the association of disease risk factors with individual microbial taxa and overall microbial community composition. This approach can naturally handle excessive numbers of zeros and the compositional data structure with the discrete part and the logistic-normal part of the model. For parameter estimation, an estimating equations approach is employed that enables us to address the complex inter-taxa correlation structure induced by the hierarchical phylogenetic tree structure and the compositional data structure. This model is able to incorporate standard regularization approaches to deal with high dimensionality. Simulation shows that our model outperforms existing methods. Our approach is also compared to others using the analysis of real microbiome data.

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arXiv2018

Generalized Linear Models with Linear Constraints for Microbiome Compositional Data

Motivated by regression analysis for microbiome compositional data, this paper considers generalized linear regression analysis with compositional covariates, where a group of linear constraints on regression coefficients are imposed to account for the compositional nature of the data and to achieve subcompositional coherence. A penalized likelihood estimation procedure using a generalized accelerated proximal gradient method is developed to efficiently estimate the regression coefficients. A de-biased procedure is developed to obtain asymptotically unbiased and normally distributed estimates, which leads to valid confidence intervals of the regression coefficients. Simulations results show the correctness of the coverage probability of the confidence intervals and smaller variances of the estimates when the appropriate linear constraints are imposed. The methods are illustrated by a microbiome study in order to identify bacterial species that are associated with inflammatory bowel disease (IBD) and to predict IBD using fecal microbiome.

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arXiv2017

Optimal detection of weak positive latent dependence between two sequences of multiple tests

It is frequently of interest to jointly analyze two paired sequences of multiple tests. This paper studies the problem of detecting whether there are more pairs of tests that are significant in both sequences than would be expected by chance. The detection boundary is derived in terms of parameters such as the sparsity of the latent significance indicators of the tests in each sequence, the effect sizes of the non-null tests, and the magnitude of the dependence between the two sequences. A new test for detecting weak dependence is also proposed, shown to be asymptotically adaptively optimal, studied in simulations, and applied to study of genetic pleiotropy in 10 pediatric autoimmune diseases.

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arXiv2017

A Model for Paired-Multinomial Data and Its Application to Analysis of Data on a Taxonomic Tree

In human microbiome studies, sequencing reads data are often summarized as counts of bacterial taxa at various taxonomic levels specified by a taxonomic tree. This paper considers the problem of analyzing two repeated measurements of microbiome data from the same subjects. Such data are often collected to assess the change of microbial composition after certain treatment, or the difference in microbial compositions across body sites. Existing models for such count data are limited in modeling the covariance structure of the counts and in handling paired multinomial count data. A new probability distribution is proposed for paired-multinomial count data, which allows flexible covariance structure and can be used to model repeatedly measured multivariate count data. Based on this distribution, a test statistic is developed for testing the difference in compositions based on paired multinomial count data. The proposed test can be applied to the count data observed on a taxonomic tree in order to test difference in microbiome compositions and to identify the subtrees with different subcompositions. Simulation results indicate that proposed test has correct type 1 errors and increased power compared to some commonly used methods. An analysis of an upper respiratory tract microbiome data set is used to illustrate the proposed methods.

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arXiv2016

Optimal Estimation of Co-heritability in High-dimensional Linear Models

Co-heritability is an important concept that characterizes the genetic associations within pairs of quantitative traits. There has been significant recent interest in estimating the co-heritability based on data from the genome-wide association studies (GWAS). This paper introduces two measures of co-heritability in the high-dimensional linear model framework, including the inner product of the two regression vectors and a normalized inner product by their lengths. Functional de-biased estimators (FDEs) are developed to estimate these two co-heritability measures. In addition, estimators of quadratic functionals of the regression vectors are proposed. Both theoretical and numerical properties of the estimators are investigated. In particular, minimax rates of convergence are established and the proposed estimators of the inner product, the quadratic functionals and the normalized inner product are shown to be rate-optimal. Simulation results show that the FDEs significantly outperform the naive plug-in estimates. The FDEs are also applied to analyze a yeast segregant data set with multiple traits to estimate heritability and co-heritability among the traits.

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arXiv2016

Regression Analysis for Microbiome Compositional Data

One important problem in microbiome analysis is to identify the bacterial taxa that are associated with a response, where the microbiome data are summarized as the composition of the bacterial taxa at different taxonomic levels. This paper considers regression analysis with such compositional data as covariates. In order to satisfy the subcompositional coherence of the results, linear models with a set of linear constraints on the regression coefficients are introduced. Such models allow regression analysis for subcompositions and include the log-contrast model for compositional covariates as a special case. A penalized estimation procedure for estimating the regression coefficients and for selecting variables under the linear constraints is developed. A method is also proposed to obtain de-biased estimates of the regression coefficients that are asymptotically unbiased and have a joint asymptotic multivariate normal distribution. This provides valid confidence intervals of the regression coefficients and can be used to obtain the $p$-values. Simulation results show the validity of the confidence intervals and smaller variances of the de-biased estimates when the linear constraints are imposed. The proposed methods are applied to a gut microbiome data set and identify four bacterial genera that are associated with the body mass index after adjusting for the total fat and caloric intakes.

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arXiv2016

Large Covariance Estimation for Compositional Data via Composition-Adjusted Thresholding

High-dimensional compositional data arise naturally in many applications such as metagenomic data analysis. The observed data lie in a high-dimensional simplex, and conventional statistical methods often fail to produce sensible results due to the unit-sum constraint. In this article, we address the problem of covariance estimation for high-dimensional compositional data, and introduce a composition-adjusted thresholding (COAT) method under the assumption that the basis covariance matrix is sparse. Our method is based on a decomposition relating the compositional covariance to the basis covariance, which is approximately identifiable as the dimensionality tends to infinity. The resulting procedure can be viewed as thresholding the sample centered log-ratio covariance matrix and hence is scalable for large covariance matrices. We rigorously characterize the identifiability of the covariance parameters, derive rates of convergence under the spectral norm, and provide theoretical guarantees on support recovery. Simulation studies demonstrate that the COAT estimator outperforms some naive thresholding estimators that ignore the unique features of compositional data. We apply the proposed method to the analysis of a microbiome dataset in order to understand the dependence structure among bacterial taxa in the human gut.

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arXiv2014

Regularization Methods for High-Dimensional Instrumental Variables Regression With an Application to Genetical Genomics

In genetical genomics studies, it is important to jointly analyze gene expression data and genetic variants in exploring their associations with complex traits, where the dimensionality of gene expressions and genetic variants can both be much larger than the sample size. Motivated by such modern applications, we consider the problem of variable selection and estimation in high-dimensional sparse instrumental variables models. To overcome the difficulty of high dimensionality and unknown optimal instruments, we propose a two-stage regularization framework for identifying and estimating important covariate effects while selecting and estimating optimal instruments. The methodology extends the classical two-stage least squares estimator to high dimensions by exploiting sparsity using sparsity-inducing penalty functions in both stages. The resulting procedure is efficiently implemented by coordinate descent optimization. For the representative $L_1$ regularization and a class of concave regularization methods, we establish estimation, prediction, and model selection properties of the two-stage regularized estimators in the high-dimensional setting where the dimensionality of covariates and instruments are both allowed to grow exponentially with the sample size. The practical performance of the proposed method is evaluated by simulation studies and its usefulness is illustrated by an analysis of mouse obesity data. Supplementary materials for this article are available online.

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