Tutorial in Biostatistics: The use of generalized additive models to evaluate alcohol consumption as an exposure variable.
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ABSTRACT:
SUBMITTER: White LF
PROVIDER: S-EPMC7171980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.
| S-EPMC3982924 | biostudies-literature
Project description:ChIP-seq experiment (IP and input control) for the general transcription factor TFIIB in S. cerevisiae
2016-12-22 | E-MTAB-4175 | biostudies-arrayexpress
Project description:PurposeTo describe and demonstrate methods for analyzing longitudinal correlated eye data with a continuous outcome measure.MethodsWe described fixed effects, mixed effects and generalized estimating equations (GEE) models, applied them to data from the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) and the Age-Related Eye Disease Study (AREDS). In CAPT (N = 1052), we assessed the effect of eye-specific laser treatment on change in visual acuity (VA). In the AREDS study, we evaluated effects of systemic supplement treatment among 1463 participants with AMD category 3.ResultsIn CAPT, the inter-eye correlations (0.33 to 0.53) and longitudinal correlations (0.31 to 0.88) varied. There was a small treatment effect on VA change (approximately one letter) at 24 months for all three models (p = .009 to 0.02). Model fit was better with the mixed effects model than the fixed effects model (p < .001). In AREDS, there was no significant treatment effect in all models (p > .55). Current smokers had a significantly greater VA decline than non-current smokers in the fixed effects model (p = .04) and the mixed effects model with random intercept (p = .0003), but marginally significant in the mixed effects model with random intercept and slope (p = .08), and GEE models (p = .054 to 0.07). The model fit was better with the fixed effects model than the mixed effects model (p < .0001).ConclusionLongitudinal models using the eye as the unit of analysis can be implemented using available statistical software to account for both inter-eye and longitudinal correlations. Goodness-of-fit statistics may guide the selection of the most appropriate model.
| S-EPMC8150110 | biostudies-literature
Project description:Modern research data, where a large number of functional predictors is collected on few subjects are becoming increasingly common. In this paper we propose a variable selection technique, when the predictors are functional and the response is scalar. Our approach is based on adopting a generalized functional linear model framework and using a penalized likelihood method that simultaneously controls the sparsity of the model and the smoothness of the corresponding coefficient functions by adequate penalization. The methodology is characterized by high predictive accuracy, and yields interpretable models, while retaining computational efficiency. The proposed method is investigated numerically in finite samples, and applied to a diffusion tensor imaging tractography data set and a chemometric data set.
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Project description:We present fast classification techniques for sparse generalized linear and additive models. These techniques can handle thousands of features and thousands of observations in minutes, even in the presence of many highly correlated features. For fast sparse logistic regression, our computational speed-up over other best-subset search techniques owes to linear and quadratic surrogate cuts for the logistic loss that allow us to efficiently screen features for elimination, as well as use of a priority queue that favors a more uniform exploration of features. As an alternative to the logistic loss, we propose the exponential loss, which permits an analytical solution to the line search at each iteration. Our algorithms are generally 2 to 5 times faster than previous approaches. They produce interpretable models that have accuracy comparable to black box models on challenging datasets.
| S-EPMC9122737 | biostudies-literature
Project description:Third-variable effect refers to the effect transmitted by third-variables that intervene in the relationship between an exposure and a response variable. Third-variable effect analysis has been broadly studied in many fields. However, it remains a challenge for researchers to differentiate indirect effect of individual factor from multiple third-variables, especially when the involving variables are of hierarchical structure. Yu et al. (2014) defined third-variable effects that were consistent for all different types of response (categorical or continuous), exposure, or third-variables. With these definitions, multiple third-variables can be considered simultaneously, and the indirect effects carried by individual third-variables can be separated from the total effect. In this paper, we extend the definitions of third-variable effects to multilevel data structures, where multilevel additive models are adapted to model the variable relationships. And then third-variable effects can be estimated at different levels. Moreover, transformations on variables are allowed to present nonlinear relationships among variables. We compile an R package mlma, to carry out the proposed multilevel third-variable analysis. Simulations show that the proposed method can effectively differentiate and estimate third-variable effects from different levels. Further, we implement the method to explore the racial disparity in body mass index accounting for both environmental and individual level risk factors.
| S-EPMC7584256 | biostudies-literature
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
Project description:The use of propensity scores to control for pretreatment imbalances on observed variables in non-randomized or observational studies examining the causal effects of treatments or interventions has become widespread over the past decade. For settings with two conditions of interest such as a treatment and a control, inverse probability of treatment weighted estimation with propensity scores estimated via boosted models has been shown in simulation studies to yield causal effect estimates with desirable properties. There are tools (e.g., the twang package in R) and guidance for implementing this method with two treatments. However, there is not such guidance for analyses of three or more treatments. The goals of this paper are twofold: (1) to provide step-by-step guidance for researchers who want to implement propensity score weighting for multiple treatments and (2) to propose the use of generalized boosted models (GBM) for estimation of the necessary propensity score weights. We define the causal quantities that may be of interest to studies of multiple treatments and derive weighted estimators of those quantities. We present a detailed plan for using GBM to estimate propensity scores and using those scores to estimate weights and causal effects. We also provide tools for assessing balance and overlap of pretreatment variables among treatment groups in the context of multiple treatments. A case study examining the effects of three treatment programs for adolescent substance abuse demonstrates the methods.
| S-EPMC3710547 | biostudies-literature
Project description:BackgroundHuman immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.MethodsIn this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.ResultsWe provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.ConclusionsThe use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.
| S-EPMC3359263 | biostudies-literature
Project description:In this paper, we discuss an extension to two popular approaches to modeling complex structures in ecological data: the generalized additive model (GAM) and the hierarchical model (HGLM). The hierarchical GAM (HGAM), allows modeling of nonlinear functional relationships between covariates and outcomes where the shape of the function itself varies between different grouping levels. We describe the theoretical connection between HGAMs, HGLMs, and GAMs, explain how to model different assumptions about the degree of intergroup variability in functional response, and show how HGAMs can be readily fitted using existing GAM software, the mgcv package in R. We also discuss computational and statistical issues with fitting these models, and demonstrate how to fit HGAMs on example data. All code and data used to generate this paper are available at: github.com/eric-pedersen/mixed-effect-gams.
| S-EPMC6542350 | biostudies-literature