Browse
Submit Data
Databases
API
Help

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using generalized linear models to implement g-estimation for survival data with time-varying confounding.

ABSTRACT: Using data from observational studies to estimate the causal effect of a time-varying exposure, repeatedly measured over time, on an outcome of interest requires careful adjustment for confounding. Standard regression adjustment for observed time-varying confounders is unsuitable, as it can eliminate part of the causal effect and induce bias. Inverse probability weighting, g-computation, and g-estimation have been proposed as being more suitable methods. G-estimation has some advantages over the other two methods, but until recently there has been a lack of flexible g-estimation methods for a survival time outcome. The recently proposed Structural Nested Cumulative Survival Time Model (SNCSTM) is such a method. Efficient estimation of the parameters of this model required bespoke software. In this article we show how the SNCSTM can be fitted efficiently via g-estimation using standard software for fitting generalised linear models. The ability to implement g-estimation for a survival outcome using standard statistical software greatly increases the potential uptake of this method. We illustrate the use of this method of fitting the SNCSTM by reanalyzing data from the UK Cystic Fibrosis Registry, and provide example R code to facilitate the use of this approach by other researchers.

SUBMITTER: Seaman SR

PROVIDER: S-EPMC7612171 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Semiparametric Analysis of Heterogeneous Data Using Varying-Scale Generalized Linear Models.

Project description:This article describes a class of heteroscedastic generalized linear regression models in which a subset of the regression parameters are rescaled nonparametrically, and develops efficient semiparametric inferences for the parametric components of the models. Such models provide a means to adapt for heterogeneity in the data due to varying exposures, varying levels of aggregation, and so on. The class of models considered includes generalized partially linear models and nonparametrically scaled link function models as special cases. We present an algorithm to estimate the scale function nonparametrically, and obtain asymptotic distribution theory for regression parameter estimates. In particular, we establish that the asymptotic covariance of the semiparametric estimator for the parametric part of the model achieves the semiparametric lower bound. We also describe bootstrap-based goodness-of-scale test. We illustrate the methodology with simulations, published data, and data from collaborative research on ultrasound safety.

| S-EPMC2681270 | biostudies-literature

Efficient estimation of generalized linear latent variable models.

Project description:Generalized linear latent variable models (GLLVM) are popular tools for modeling multivariate, correlated responses. Such data are often encountered, for instance, in ecological studies, where presence-absences, counts, or biomass of interacting species are collected from a set of sites. Until very recently, the main challenge in fitting GLLVMs has been the lack of computationally efficient estimation methods. For likelihood based estimation, several closed form approximations for the marginal likelihood of GLLVMs have been proposed, but their efficient implementations have been lacking in the literature. To fill this gap, we show in this paper how to obtain computationally convenient estimation algorithms based on a combination of either the Laplace approximation method or variational approximation method, and automatic optimization techniques implemented in R software. An extensive set of simulation studies is used to assess the performances of different methods, from which it is shown that the variational approximation method used in conjunction with automatic optimization offers a powerful tool for estimation.

| S-EPMC6493759 | biostudies-literature

Penalized Quadratic Inference Function-Based Variable Selection for Generalized Partially Linear Varying Coefficient Models with Longitudinal Data.

Project description:Semiparametric generalized varying coefficient partially linear models with longitudinal data arise in contemporary biology, medicine, and life science. In this paper, we consider a variable selection procedure based on the combination of the basis function approximations and quadratic inference functions with SCAD penalty. The proposed procedure simultaneously selects significant variables in the parametric components and the nonparametric components. With appropriate selection of the tuning parameters, we establish the consistency, sparsity, and asymptotic normality of the resulting estimators. The finite sample performance of the proposed methods is evaluated through extensive simulation studies and a real data analysis.

| S-EPMC7556090 | biostudies-literature

Quantifying time-varying cellular secretions with local linear models.

Project description:Extracellular protein concentrations and gradients initiate a wide range of cellular responses, such as cell motility, growth, proliferation and death. Understanding inter-cellular communication requires spatio-temporal knowledge of these secreted factors and their causal relationship with cell phenotype. Techniques which can detect cellular secretions in real time are becoming more common but generalizable data analysis methodologies which can quantify concentration from these measurements are still lacking. Here we introduce a probabilistic approach in which local-linear models and the law of mass action are applied to obtain time-varying secreted concentrations from affinity-based biosensor data. We first highlight the general features of this approach using simulated data which contains both static and time-varying concentration profiles. Next we apply the technique to determine concentration of secreted antibodies from 9E10 hybridoma cells as detected using nanoplasmonic biosensors. A broad range of time-dependent concentrations was observed: from steady-state secretions of 230 pM near the cell surface to large transients which reached as high as 56 nM over several minutes and then dissipated.

| S-EPMC5506887 | biostudies-other

Heritability estimation and differential analysis of count data with generalized linear mixed models in genomic sequencing studies.

Project description:MotivationGenomic sequencing studies, including RNA sequencing and bisulfite sequencing studies, are becoming increasingly common and increasingly large. Large genomic sequencing studies open doors for accurate molecular trait heritability estimation and powerful differential analysis. Heritability estimation and differential analysis in sequencing studies requires the development of statistical methods that can properly account for the count nature of the sequencing data and that are computationally efficient for large datasets.ResultsHere, we develop such a method, PQLseq (Penalized Quasi-Likelihood for sequencing count data), to enable effective and efficient heritability estimation and differential analysis using the generalized linear mixed model framework. With extensive simulations and comparisons to previous methods, we show that PQLseq is the only method currently available that can produce unbiased heritability estimates for sequencing count data. In addition, we show that PQLseq is well suited for differential analysis in large sequencing studies, providing calibrated type I error control and more power compared to the standard linear mixed model methods. Finally, we apply PQLseq to perform gene expression heritability estimation and differential expression analysis in a large RNA sequencing study in the Hutterites.Availability and implementationPQLseq is implemented as an R package with source code freely available at www.xzlab.org/software.html and https://cran.r-project.org/web/packages/PQLseq/index.html.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC6361238 | biostudies-literature

Bayesian imputation of time-varying covariates in linear mixed models.

Project description:Studies involving large observational datasets commonly face the challenge of dealing with multiple missing values. The most popular approach to overcome this challenge, multiple imputation using chained equations, however, has been shown to be sub-optimal in complex settings, specifically in settings with longitudinal outcomes, which cannot be easily and adequately included in the imputation models. Bayesian methods avoid this difficulty by specification of a joint distribution and thus offer an alternative. A popular choice for that joint distribution is the multivariate normal distribution. In more complicated settings, as in our two motivating examples that involve time-varying covariates, additional issues require consideration: the endo- or exogeneity of the covariate and its functional relation with the outcome. In such situations, the implied assumptions of standard methods may be violated, resulting in bias. In this work, we extend and study a more flexible, Bayesian alternative to the multivariate normal approach, to better handle complex incomplete longitudinal data. We discuss and compare assumptions of the two Bayesian approaches about the endo- or exogeneity of the covariates and the functional form of the association with the outcome, and illustrate and evaluate consequences of violations of those assumptions using simulation studies and two real data examples.

| S-EPMC6344996 | biostudies-literature

To transform or not to transform: using generalized linear mixed models to analyse reaction time data.

Project description:Linear mixed-effect models (LMMs) are being increasingly widely used in psychology to analyse multi-level research designs. This feature allows LMMs to address some of the problems identified by Speelman and McGann (2013) about the use of mean data, because they do not average across individual responses. However, recent guidelines for using LMM to analyse skewed reaction time (RT) data collected in many cognitive psychological studies recommend the application of non-linear transformations to satisfy assumptions of normality. Uncritical adoption of this recommendation has important theoretical implications which can yield misleading conclusions. For example, Balota et al. (2013) showed that analyses of raw RT produced additive effects of word frequency and stimulus quality on word identification, which conflicted with the interactive effects observed in analyses of transformed RT. Generalized linear mixed-effect models (GLMM) provide a solution to this problem by satisfying normality assumptions without the need for transformation. This allows differences between individuals to be properly assessed, using the metric most appropriate to the researcher's theoretical context. We outline the major theoretical decisions involved in specifying a GLMM, and illustrate them by reanalysing Balota et al.'s datasets. We then consider the broader benefits of using GLMM to investigate individual differences.

| S-EPMC4528092 | biostudies-literature

Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data.

Project description:The generalized semiparametric mixed varying-coefficient effects model for longitudinal data can accommodate a variety of link functions and flexibly model different types of covariate effects, including time-constant, time-varying, and covariate-varying effects. The time-varying effects are unspecified functions of time and the covariate-varying effects are nonparametric functions of a possibly time-dependent exposure variable. A semiparametric estimation procedure is developed that uses local linear smoothing and profile weighted least squares, which requires smoothing in the two different and yet connected domains of time and the time-dependent exposure variable. The asymptotic properties of the estimators of both nonparametric and parametric effects are investigated. In addition, hypothesis testing procedures are developed to examine the covariate effects. The finite-sample properties of the proposed estimators and testing procedures are examined through simulations, indicating satisfactory performances. The proposed methods are applied to analyze the ACTG 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV-infected patients before and after developing the T215Y antiretroviral drug resistance mutation.

| S-EPMC6905629 | biostudies-literature

An assessment of estimation methods for generalized linear mixed models with binary outcomes.

Project description:Two main classes of methodology have been developed for addressing the analytical intractability of generalized linear mixed models: likelihood-based methods and Bayesian methods. Likelihood-based methods such as the penalized quasi-likelihood approach have been shown to produce biased estimates especially for binary clustered data with small clusters sizes. More recent methods using adaptive Gaussian quadrature perform well but can be overwhelmed by problems with large numbers of random effects, and efficient algorithms to better handle these situations have not yet been integrated in standard statistical packages. Bayesian methods, although they have good frequentist properties when the model is correct, are known to be computationally intensive and also require specialized code, limiting their use in practice. In this article, we introduce a modification of the hybrid approach of Capanu and Begg, 2011, Biometrics 67, 371-380, as a bridge between the likelihood-based and Bayesian approaches by employing Bayesian estimation for the variance components followed by Laplacian estimation for the regression coefficients. We investigate its performance as well as that of several likelihood-based methods in the setting of generalized linear mixed models with binary outcomes. We apply the methods to three datasets and conduct simulations to illustrate their properties. Simulation results indicate that for moderate to large numbers of observations per random effect, adaptive Gaussian quadrature and the Laplacian approximation are very accurate, with adaptive Gaussian quadrature preferable as the number of observations per random effect increases. The hybrid approach is overall similar to the Laplace method, and it can be superior for data with very sparse random effects.

| S-EPMC3866838 | biostudies-literature

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

Project description: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.

| S-EPMC8442657 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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