Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Estimation and Inference for High Dimensional Generalized Linear Models: A Splitting and Smoothing Approach.

ABSTRACT: The focus of modern biomedical studies has gradually shifted to explanation and estimation of joint effects of high dimensional predictors on disease risks. Quantifying uncertainty in these estimates may provide valuable insight into prevention strategies or treatment decisions for both patients and physicians. High dimensional inference, including confidence intervals and hypothesis testing, has sparked much interest. While much work has been done in the linear regression setting, there is lack of literature on inference for high dimensional generalized linear models. We propose a novel and computationally feasible method, which accommodates a variety of outcome types, including normal, binomial, and Poisson data. We use a "splitting and smoothing" approach, which splits samples into two parts, performs variable selection using one part and conducts partial regression with the other part. Averaging the estimates over multiple random splits, we obtain the smoothed estimates, which are numerically stable. We show that the estimates are consistent, asymptotically normal, and construct confidence intervals with proper coverage probabilities for all predictors. We examine the finite sample performance of our method by comparing it with the existing methods and applying it to analyze a lung cancer cohort study.

SUBMITTER: Fei Z

PROVIDER: S-EPMC8442657 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Statistical Inference for High-Dimensional Generalized Linear Models with Binary Outcomes.

Project description:This paper develops a unified statistical inference framework for high-dimensional binary generalized linear models (GLMs) with general link functions. Both unknown and known design distribution settings are considered. A two-step weighted bias-correction method is proposed for constructing confidence intervals and simultaneous hypothesis tests for individual components of the regression vector. Minimax lower bound for the expected length is established and the proposed confidence intervals are shown to be rate-optimal up to a logarithmic factor. The numerical performance of the proposed procedure is demonstrated through simulation studies and an analysis of a single cell RNA-seq data set, which yields interesting biological insights that integrate well into the current literature on the cellular immune response mechanisms as characterized by single-cell transcriptomics. The theoretical analysis provides important insights on the adaptivity of optimal confidence intervals with respect to the sparsity of the regression vector. New lower bound techniques are introduced and they can be of independent interest to solve other inference problems in high-dimensional binary GLMs.

| S-EPMC10292730 | biostudies-literature

Markov neighborhood regression for statistical inference of high-dimensional generalized linear models.

Project description:High-dimensional inference is one of fundamental problems in modern biomedical studies. However, the existing methods do not perform satisfactorily. Based on the Markov property of graphical models and the likelihood ratio test, this article provides a simple justification for the Markov neighborhood regression method such that it can be applied to statistical inference for high-dimensional generalized linear models with mixed features. The Markov neighborhood regression method is highly attractive in that it breaks the high-dimensional inference problems into a series of low-dimensional inference problems. The proposed method is applied to the cancer cell line encyclopedia data for identification of the genes and mutations that are sensitive to the response of anti-cancer drugs. The numerical results favor the Markov neighborhood regression method to the existing ones.

| S-EPMC9427730 | biostudies-literature

Estimation and inference for the indirect effect in high-dimensional linear mediation models.

Project description:Mediation analysis is difficult when the number of potential mediators is larger than the sample size. In this paper we propose new inference procedures for the indirect effect in the presence of high-dimensional mediators for linear mediation models. We develop methods for both incomplete mediation, where a direct effect may exist, and complete mediation, where the direct effect is known to be absent. We prove consistency and asymptotic normality of our indirect effect estimators. Under complete mediation, where the indirect effect is equivalent to the total effect, we further prove that our approach gives a more powerful test compared to directly testing for the total effect. We confirm our theoretical results in simulations, as well as in an integrative analysis of gene expression and genotype data from a pharmacogenomic study of drug response. We present a novel analysis of gene sets to understand the molecular mechanisms of drug response, and also identify a genome-wide significant noncoding genetic variant that cannot be detected using standard analysis methods.

| S-EPMC7430942 | biostudies-literature

LINEAR HYPOTHESIS TESTING FOR HIGH DIMENSIONAL GENERALIZED LINEAR MODELS.

Project description:This paper is concerned with testing linear hypotheses in high-dimensional generalized linear models. To deal with linear hypotheses, we first propose constrained partial regularization method and study its statistical properties. We further introduce an algorithm for solving regularization problems with folded-concave penalty functions and linear constraints. To test linear hypotheses, we propose a partial penalized likelihood ratio test, a partial penalized score test and a partial penalized Wald test. We show that the limiting null distributions of these three test statistics are ?2 distribution with the same degrees of freedom, and under local alternatives, they asymptotically follow non-central ?2 distributions with the same degrees of freedom and noncentral parameter, provided the number of parameters involved in the test hypothesis grows to ? at a certain rate. Simulation studies are conducted to examine the finite sample performance of the proposed tests. Empirical analysis of a real data example is used to illustrate the proposed testing procedures.

| S-EPMC6750760 | biostudies-literature

Drawing inferences for high-dimensional linear models: A selection-assisted partial regression and smoothing approach.

Project description:Drawing inferences for high-dimensional models is challenging as regular asymptotic theories are not applicable. This article proposes a new framework of simultaneous estimation and inferences for high-dimensional linear models. By smoothing over partial regression estimates based on a given variable selection scheme, we reduce the problem to low-dimensional least squares estimations. The procedure, termed as Selection-assisted Partial Regression and Smoothing (SPARES), utilizes data splitting along with variable selection and partial regression. We show that the SPARES estimator is asymptotically unbiased and normal, and derive its variance via a nonparametric delta method. The utility of the procedure is evaluated under various simulation scenarios and via comparisons with the de-biased LASSO estimators, a major competitor. We apply the method to analyze two genomic datasets and obtain biologically meaningful results.

| S-EPMC6570588 | biostudies-literature

Inference for high-dimensional linear mixed-effects models: A quasi-likelihood approach.

Project description:Linear mixed-effects models are widely used in analyzing clustered or repeated measures data. We propose a quasi-likelihood approach for estimation and inference of the unknown parameters in linear mixed-effects models with high-dimensional fixed effects. The proposed method is applicable to general settings where the dimension of the random effects and the cluster sizes are possibly large. Regarding the fixed effects, we provide rate optimal estimators and valid inference procedures that do not rely on the structural information of the variance components. We also study the estimation of variance components with high-dimensional fixed effects in general settings. The algorithms are easy to implement and computationally fast. The proposed methods are assessed in various simulation settings and are applied to a real study regarding the associations between body mass index and genetic polymorphic markers in a heterogeneous stock mice population.

| S-EPMC9928173 | biostudies-literature

Estimation and Inference in Generalized Additive Coefficient Models for Nonlinear Interactions with High-Dimensional Covariates.

Project description:In the low-dimensional case, the generalized additive coefficient model (GACM) proposed by Xue and Yang [Statist. Sinica16 (2006) 1423-1446] has been demonstrated to be a powerful tool for studying nonlinear interaction effects of variables. In this paper, we propose estimation and inference procedures for the GACM when the dimension of the variables is high. Specifically, we propose a groupwise penalization based procedure to distinguish significant covariates for the "large p small n" setting. The procedure is shown to be consistent for model structure identification. Further, we construct simultaneous confidence bands for the coefficient functions in the selected model based on a refined two-step spline estimator. We also discuss how to choose the tuning parameters. To estimate the standard deviation of the functional estimator, we adopt the smoothed bootstrap method. We conduct simulation experiments to evaluate the numerical performance of the proposed methods and analyze an obesity data set from a genome-wide association study as an illustration.

| S-EPMC4578655 | biostudies-literature

Testing generalized linear models with high-dimensional nuisance parameter.

Project description:Generalized linear models often have a high-dimensional nuisance parameters, as seen in applications such as testing gene-environment interactions or gene-gene interactions. In these scenarios, it is essential to test the significance of a high-dimensional sub-vector of the model's coefficients. Although some existing methods can tackle this problem, they often rely on the bootstrap to approximate the asymptotic distribution of the test statistic, and thus are computationally expensive. Here, we propose a computationally efficient test with a closed-form limiting distribution, which allows the parameter being tested to be either sparse or dense. We show that under certain regularity conditions, the type I error of the proposed method is asymptotically correct, and we establish its power under high-dimensional alternatives. Extensive simulations demonstrate the good performance of the proposed test and its robustness when certain sparsity assumptions are violated. We also apply the proposed method to Chinese famine sample data in order to show its performance when testing the significance of gene-environment interactions.

| S-EPMC9933885 | biostudies-literature

Weight Smoothing for Generalized Linear Models Using a Laplace Prior.

Project description:When analyzing data sampled with unequal inclusion probabilities, correlations between the probability of selection and the sampled data can induce bias if the inclusion probabilities are ignored in the analysis. Weights equal to the inverse of the probability of inclusion are commonly used to correct possible bias. When weights are uncorrelated with the descriptive or model estimators of interest, highly disproportional sample designs resulting in large weights can introduce unnecessary variability, leading to an overall larger mean square error compared to unweighted methods. We describe an approach we term 'weight smoothing' that models the interactions between the weights and the estimators as random effects, reducing the root mean square error (RMSE) by shrinking interactions toward zero when such shrinkage is allowed by the data. This article adapts a flexible Laplace prior distribution for the hierarchical Bayesian model to gain a more robust bias-variance tradeoff than previous approaches using normal priors. Simulation and application suggest that under a linear model setting, weight-smoothing models with Laplace priors yield robust results when weighting is necessary, and provide considerable reduction in RMSE otherwise. In logistic regression models, estimates using weight-smoothing models with Laplace priors are robust, but with less gain in efficiency than in linear regression settings.

| S-EPMC5719898 | biostudies-literature

Bayesian inference for generalized linear mixed models.

Project description:Generalized linear mixed models (GLMMs) continue to grow in popularity due to their ability to directly acknowledge multiple levels of dependency and model different data types. For small sample sizes especially, likelihood-based inference can be unreliable with variance components being particularly difficult to estimate. A Bayesian approach is appealing but has been hampered by the lack of a fast implementation, and the difficulty in specifying prior distributions with variance components again being particularly problematic. Here, we briefly review previous approaches to computation in Bayesian implementations of GLMMs and illustrate in detail, the use of integrated nested Laplace approximations in this context. We consider a number of examples, carefully specifying prior distributions on meaningful quantities in each case. The examples cover a wide range of data types including those requiring smoothing over time and a relatively complicated spline model for which we examine our prior specification in terms of the implied degrees of freedom. We conclude that Bayesian inference is now practically feasible for GLMMs and provides an attractive alternative to likelihood-based approaches such as penalized quasi-likelihood. As with likelihood-based approaches, great care is required in the analysis of clustered binary data since approximation strategies may be less accurate for such data.

| S-EPMC2883299 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data