Modeling non-linear temporal trajectories is of fundamental interest in many application areas, such as in longitudinal microbiome analysis. Many existing methods focus on estimating mean trajectories, but it is also often of value to assess temporal patterns of individual subjects. Sparse principal components analysis (SFPCA) serves as a useful tool for assessing individual variation in non-linear trajectories; however its application to real data often requires careful model selection criteria and diagnostic tools. Here, we propose a Bayesian approach to SFPCA, which allows users to use the efficient leave-one-out cross-validation (LOO) with Pareto-smoothed importance sampling (PSIS) for model selection, and to utilize the estimated shape parameter from PSIS-LOO and also the posterior predictive checks for graphical model diagnostics. This Bayesian implementation thus enables careful application of SFPCA to a wide range of longitudinal data applications.
This paper takes a quick look at Bayesian joint models (BJM) for longitudinal and survival data. A general formulation for BJM is examined in terms of the sampling distribution of the longitudinal and survival processes, the conditional distribution of the random effects and the prior distribution. Next a basic BJM defined in terms of a mixed linear model and a Cox survival regression models is discussed and some extensions and other Bayesian topics are briefly outlined.
Understanding how adult humans learn non-native speech categories such as tone information has shed novel insights into the mechanisms underlying experience-dependent brain plasticity. Scientists have traditionally examined these questions using longitudinal learning experiments under a multi-category decision making paradigm. Drift-diffusion processes are popular in such contexts for their ability to mimic underlying neural mechanisms. Motivated by these problems, we develop a novel Bayesian semiparametric inverse Gaussian drift-diffusion mixed model for multi-alternative decision making in l…
Principal component regression uses principal components as regressors. It is particularly useful in prediction settings with high-dimensional covariates. The existing literature treating of Bayesian approaches is relatively sparse. We introduce a Bayesian approach that is robust to outliers in both the dependent variable and the covariates. Outliers can be thought of as observations that are not in line with the general trend. The proposed approach automatically penalises these observations so that their impact on the posterior gradually vanishes as they move further and further away from the…
We propose a Bayesian inference approach for a class of latent Markov models. These models are widely used for the analysis of longitudinal categorical data, when the interest is in studying the evolution of an individual unobservable characteristic. We consider, in particular, the basic latent Markov, which does not account for individual covariates, and its version that includes such covariates in the measurement model. The proposed inferential approach is based on a system of priors formulated on a transformation of the initial and transition probabilities of the latent Markov chain. This s…
Trial-based economic evaluations are typically performed on cross-sectional variables, derived from the responses for only the completers in the study, using methods that ignore the complexities of utility and cost data (e.g. skewness and spikes). We present an alternative and more efficient Bayesian parametric approach to handle missing longitudinal outcomes in economic evaluations, while accounting for the complexities of the data. We specify a flexible parametric model for the observed data and partially identify the distribution of the missing data with partial identifying restrictions and…
The article develops marginal models for multivariate longitudinal responses. Overall, the model consists of five regression submodels, one for the mean and four for the covariance matrix, with the latter resulting by considering various matrix decompositions. The decompositions that we employ are intuitive, easy to understand, and they do not rely on any assumptions such as the presence of an ordering among the multivariate responses. The regression submodels are semiparametric, with unknown functions represented by basis function expansions. We use spike-slap priors for the regression coeffi…
Functional principal components analysis is a popular tool for inference on functional data. Standard approaches rely on an eigendecomposition of a smoothed covariance surface in order to extract the orthonormal functions representing the major modes of variation. This approach can be a computationally intensive procedure, especially in the presence of large datasets with irregular observations. In this article, we develop a Bayesian approach, which aims to determine the Karhunen-Loève decomposition directly without the need to smooth and estimate a covariance surface. More specifically, we de…
Preclinical Alzheimer's disease (AD), the earliest stage in the AD continuum, can last fifteen to twenty years, with cognitive decline trajectories nonlinear and heterogeneous between subjects. Characterizing cognitive decline in the preclinical phase of AD is critical for the development of early intervention strategies when disease-modifying therapies may be most effective. In the last decade, there has been an increased interest in the application of change point (CP) models to longitudinal cognitive outcomes. Because patients' change points can vary greatly, it is essential to model this v…
Microbiome researchers often need to model the temporal dynamics of multiple complex, nonlinear outcome trajectories simultaneously. This motivates our development of multivariate Sparse Functional Principal Components Analysis (mSFPCA), extending existing SFPCA methods to simultaneously characterize multiple temporal trajectories and their inter-relationships. As with existing SFPCA methods, the mSFPCA algorithm characterizes each trajectory as a smooth mean plus a weighted combination of the smooth major modes of variation about the mean, where the weights are given by the component scores f…
Joint models for a wide class of response variables and longitudinal measurements consist on a mixed-effects model to fit longitudinal trajectories whose random effects enter as covariates in a generalized linear model for the primary response. They provide a useful way to asses association between these two kinds of data, which in clinical studies are often collected jointly on a series of individuals and may help understanding, for instance, the mechanisms of recovery of a certain disease or the efficacy of a given therapy. The most common joint model in this framework is based on a linear m…
In many longitudinal studies, the covariate and response are often intermittently observed at irregular, mismatched and subject-specific times. How to deal with such data when covariate and response are observed asynchronously is an often raised problem. Bayesian Additive Regression Trees(BART) is a Bayesian non-Parametric approach which has been shown to be competitive with the best modern predictive methods such as random forest and boosted decision trees. The sum of trees structure combined with a Bayesian inferential framework provide a accurate and robust statistic method. BART variant so…
Bayesian joint modelling using semiparametric accelerated failure time approaches
The University of Queensland’s Clinical Trials Capability (ULTRA)（昆士兰大学临床试验能力中心（ULTRA））；NHMRC Clinical Trial Centre, University of Sydney（悉尼大学国家健康与医学研究委员会临床试验中心）；Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group（澳大利亚和新西兰泌尿生殖和前列腺癌症试验组）
Studies of memory trajectories using longitudinal data often result in highly non-representative samples due to selective study enrollment and attrition. An additional bias comes from practice effects that result in improved or maintained performance due to familiarity with test content or context. These challenges may bias study findings and severely distort the ability to generalize to the target population. In this study we propose an approach for estimating the finite population mean of a longitudinal outcome conditioning on being alive at a specific time point. We develop a flexible Bayes…
Joint models of longitudinal and survival data have become an important tool for modeling associations between longitudinal biomarkers and event processes. The association between marker and log-hazard is assumed to be linear in existing shared random effects models, with this assumption usually remaining unchecked. We present an extended framework of flexible additive joint models that allows the estimation of nonlinear, covariate specific associations by making use of Bayesian P-splines. Our joint models are estimated in a Bayesian framework using structured additive predictors for all model…
Access and adherence to antiretroviral therapy (ART) has transformed the face of HIV infection from a fatal to a chronic disease. However, ART is also known for its side effects. Studies have reported that ART is associated with depressive symptomatology. Large-scale HIV clinical databases with individuals' longitudinal depression records, ART medications, and clinical characteristics offer researchers unprecedented opportunities to study the effects of ART drugs on depression over time. We develop BAGEL, a Bayesian graphical model to investigate longitudinal effects of ART drugs on a range of…
Characterization of long-term disease dynamics, from disease-free to end-stage, is integral to understanding the course of neurodegenerative diseases such as Parkinson's and Alzheimer's; and ultimately, how best to intervene. Natural history studies typically recruit multiple cohorts at different stages of disease and follow them longitudinally for a relatively short period of time. We propose a latent time joint mixed effects model to characterize long-term disease dynamics using this short-term data. Markov chain Monte Carlo methods are proposed for estimation, model selection, and inference…
Longitudinal Outcomes Truncated by Death: Causal Estimands and Bayesian Estimators
Amsterdam UMC（阿姆斯特丹大学医学中心）；Singapore University of Technology and Design（新加坡科技设计大学）；Massachusetts General Hospital（麻省总医院）；Harvard Medical School（哈佛医学院）
The extraordinary advancements in neuroscientific technology for brain recordings over the last decades have led to increasingly complex spatio-temporal datasets. To reduce oversimplifications, new models have been developed to be able to identify meaningful patterns and new insights within a highly demanding data environment. To this extent, we propose a new model called parameter clustering functional Principal Component Analysis (PCl-fPCA) that merges ideas from Functional Data Analysis and Bayesian nonparametrics to obtain a flexible and computationally feasible signal reconstruction and e…
The identification of sets of co-regulated genes that share a common function is a key question of modern genomics. Bayesian profile regression is a semi-supervised mixture modelling approach that makes use of a response to guide inference toward relevant clusterings. Previous applications of profile regression have considered univariate continuous, categorical, and count outcomes. In this work, we extend Bayesian profile regression to cases where the outcome is longitudinal (or multivariate continuous) and provide PReMiuMlongi, an updated version of PReMiuM, the R package for profile regressi…
Multi-dimensional functional data arises in numerous modern scientific experimental and observational studies. In this paper we focus on longitudinal functional data, a structured form of multidimensional functional data. Operating within a longitudinal functional framework we aim to capture low dimensional interpretable features. We propose a computationally efficient nonparametric Bayesian method to simultaneously smooth observed data, estimate conditional functional means and functional covariance surfaces. Statistical inference is based on Monte Carlo samples from the posterior measure thr…
In high-dimensional prediction problems, where the number of features may greatly exceed the number of training instances, fully Bayesian approach with a sparsifying prior is known to produce good results but is computationally challenging. To alleviate this computational burden, we propose to use a preprocessing step where we first apply a dimension reduction to the original data to reduce the number of features to something that is computationally conveniently handled by Bayesian methods. To do this, we propose a new dimension reduction technique, called iterative supervised principal compon…
This introduction to Bayesian statistics presents the main concepts as well as the principal reasons advocated in favour of a Bayesian modelling. We cover the various approaches to prior determination as well as the basis asymptotic arguments in favour of using Bayes estimators. The testing aspects of Bayesian inference are also examined in details.
Bayesian joint modelling of longitudinal biomarkers to enable extrapolation of overall survival: an application using larotrectinib trial clinical data
Regression-based optimal fingerprinting techniques for climate change detection and attribution require the estimation of the forced signal as well as the internal variability covariance matrix in order to distinguish between their influences in the observational record. While previously developed approaches have taken into account the uncertainty linked to the estimation of the forced signal, there has been less focus on uncertainty in the covariance matrix describing natural variability, despite the fact that the specification of this covariance matrix is known to meaningfully impact the res…
We discuss the problem of estimating the number of principal components in Principal Com- ponents Analysis (PCA). Despite of the importance of the problem and the multitude of solutions proposed in the literature, it comes as a surprise that there does not exist a coherent asymptotic framework which would justify different approaches depending on the actual size of the data set. In this paper we address this issue by presenting an approximate Bayesian approach based on Laplace approximation and introducing a general method for building the model selection criteria, called PEnalized SEmi-integr…
Two-part joint models for a longitudinal semicontinuous biomarker and a terminal event have been recently introduced based on frequentist estimation. The biomarker distribution is decomposed into a probability of positive value and the expected value among positive values. Shared random effects can represent the association structure between the biomarker and the terminal event. The computational burden increases compared to standard joint models with a single regression model for the biomarker. In this context, the frequentist estimation implemented in the R package frailtypack can be challen…
Motivated by genetic association studies of pleiotropy, we propose here a Bayesian latent variable approach to jointly study multiple outcomes or phenotypes. The proposed method models both continuous and binary phenotypes, and it accounts for serial and familial correlations when longitudinal and pedigree data have been collected. We present a Bayesian estimation method for the model parameters, and we develop a novel MCMC algorithm that builds upon hierarchical centering and parameter expansion techniques to efficiently sample the posterior distribution. We discuss phenotype and model select…
We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modelled using generalised linear mixed models, while the survival process is modelled using a parametric general hazard structure. The two processes are linked by sharing fixed and random effects, separating the effects that play a role at the time scale from those that affect the hazard scale. This strategy allows for the inclusion of non-linear and time-dependent effects while avoiding the need for numerical integration, which facilitates the implementati…
