Learning from a lot: Empirical Bayes for high‐dimensional model‐based prediction

Empirical Bayes is a versatile approach to “learn from a lot” in two ways: first, from a large number of variables and, second, from a potentially large amount of prior information, for example, stored in public repositories. We review applications of a variety of empirical Bayes methods to several well‐known model‐based prediction methods, including penalized regression, linear discriminant analysis, and Bayesian models with sparse or dense priors. We discuss “formal” empirical Bayes methods that maximize the marginal likelihood but also more informal approaches based on other data summaries. We contrast empirical Bayes to cross‐validation and full Bayes and discuss hybrid approaches. To study the relation between the quality of an empirical Bayes estimator and p, the number of variables, we consider a simple empirical Bayes estimator in a linear model setting. We argue that empirical Bayes is particularly useful when the prior contains multiple parameters, which model a priori information on variables termed “co‐data”. In particular, we present two novel examples that allow for co‐data: first, a Bayesian spike‐and‐slab setting that facilitates inclusion of multiple co‐data sources and types and, second, a hybrid empirical Bayes–full Bayes ridge regression approach for estimation of the posterior predictive interval.     

Bayesian analysis of multivariate mortality data with large families

This paper presents a Bayesian method for the analysis of toxicological multivariate mortality data when the discrete mortality rate for each family of subjects at a given time depends on familial random effects and the toxicity level experienced by the family. Our aim is to model and analyse one set of such multivariate mortality data with large family sizes: the potassium thiocyanate (KSCN) tainted fish tank data of O'Hara Hines. The model used is based on a discretized hazard with additional time-varying familial random effects. A similar previous study (using sodium thiocyanate (NaSCN)) is used to construct a prior for the parameters in the current study. A simulation-based approach is used to compute posterior estimates of the model parameters and mortality rates and several other quantities of interest. Recent tools in Bayesian model diagnostics and variable subset selection have been incorporated to verify important modelling assumptions regarding the effects of time and heterogeneity among the families on the mortality rate. Further, Bayesian methods using predictive distributions are used for comparing several plausible models.     

Bayesian incidence analysis of animal tumorigenicity data

Statistical inference about tumorigenesis should focus on the tumour incidence rate. Unfortunately, in most animal carcinogenicity experiments, tumours are not observable in live animals and censoring of the tumour onset times is informative. In this paper, we propose a Bayesian method for analysing data from such studies. Our approach focuses on the incidence of tumours and accommodates occult tumours and censored onset times without restricting tumour lethality, relying on cause-of-death data, or requiring interim sacrifices. We represent the underlying state of nature by a multistate stochastic process and assume general probit models for the time-specific transition rates. These models allow the incorporation of covariates, historical control data and subjective prior information. The inherent flexibility of this approach facilitates the interpretation of results, particularly when the sample size is small or the data are sparse. We use a Gibbs sampler to estimate the relevant posterior distributions. The methods proposed are applied to data from a US National Toxicology Program carcinogenicity study.     

A Potts‐mixture spatiotemporal joint model for combined magnetoencephalography and electroencephalography data

We develop a new methodology for determining the location and dynamics of brain activity from combined magnetoencephalography (MEG) and electroencephalography (EEG) data. The resulting inverse problem is ill‐posed and is one of the most difficult problems in neuroimaging data analysis. In our development we propose a solution that combines the data from three different modalities, magnetic resonance imaging (MRI), MEG and EEG, together. We propose a new Bayesian spatial finite mixture model that builds on the mesostate‐space model developed by Daunizeau & Friston [Daunizeau and Friston, NeuroImage 2007; 38, 67–81]. Our new model incorporates two major extensions: (i) We combine EEG and MEG data together and formulate a joint model for dealing with the two modalities simultaneously; (ii) we incorporate the Potts model to represent the spatial dependence in an allocation process that partitions the cortical surface into a small number of latent states termed mesostates. The cortical surface is obtained from MRI. We formulate the new spatiotemporal model and derive an efficient procedure for simultaneous point estimation and model selection based on the iterated conditional modes algorithm combined with local polynomial smoothing. The proposed method results in a novel estimator for the number of mixture components and is able to select active brain regions, which correspond to active variables in a high‐dimensional dynamic linear model. The methodology is investigated using synthetic data and simulation studies and then demonstrated on an application examining the neural response to the perception of scrambled faces. R software implementing the methodology along with several sample datasets are available at the following GitHub repository https://github.com/v2south/PottsMix . The Canadian Journal of Statistics 47: 688–711; 2019 © 2019 Statistical Society of Canada     

Conjugate analysis of multivariate normal data with incomplete observations

The authors discuss prior distributions that are conjugate to the multivariate normal likelihood when some of the observations are incomplete. They present a general class of priors for incorporating information about unidentified parameters in the covariance matrix. They analyze the special case of monotone patterns of missing data, providing an explicit recursive form for the posterior distribution resulting from a conjugate prior distribution. They develop an importance sampling and a Gibbs sampling approach to sample from a general posterior distribution and compare the two methods.     

Bayesian analysis of generalized odds-rate hazards models for survival data

In the analysis of censored survival data Cox proportional hazards model (1972) is extremely popular among the practitioners. However, in many real-life situations the proportionality of the hazard ratios does not seem to be an appropriate assumption. To overcome such a problem, we consider a class of nonproportional hazards models known as generalized odds-rate class of regression models. The class is general enough to include several commonly used models, such as proportional hazards model, proportional odds model, and accelerated life time model. The theoretical and computational properties of these models have been re-examined. The propriety of the posterior has been established under some mild conditions. A simulation study is conducted and a detailed analysis of the data from a prostate cancer study is presented to further illustrate the proposed methodology.     

Bayesian analysis of mark‐recapture data with travel time‐dependent survival probabilities

The authors extend the classical Cormack‐Jolly‐Seber mark‐recapture model to account for both temporal and spatial movement through a series of markers (e.g., dams). Survival rates are modeled as a function of (possibly) unobserved travel times. Because of the complex nature of the likelihood, they use a Bayesian approach based on the complete data likelihood, and integrate the posterior through Markov chain Monte Carlo methods. They test the model through simulations and apply it also to actual salmon data arising from the Columbia river system. The methodology was developed for use by the Pacific Ocean Shelf Tracking (POST) project.     

Bayesian analysis of longitudinal ordered data with flexible random effects using McMC: application to diabetic macular Edema data

In the analysis of correlated ordered data, mixed-effect models are frequently used to control the subject heterogeneity effects. A common assumption in fitting these models is the normality of random effects. In many cases, this is unrealistic, making the estimation results unreliable. This paper considers several flexible models for random effects and investigates their properties in the model fitting. We adopt a proportional odds logistic regression model and incorporate the skewed version of the normal, Student's t and slash distributions for the effects. Stochastic representations for various flexible distributions are proposed afterwards based on the mixing strategy approach. This reduces the computational burden being performed by the McMC technique. Furthermore, this paper addresses the identifiability restrictions and suggests a procedure to handle this issue. We analyze a real data set taken from an ophthalmic clinical trial. Model selection is performed by suitable Bayesian model selection criteria.     

Regression analysis of longitudinal data with outcome‐dependent sampling and informative censoring

We consider a regression analysis of longitudinal data in the presence of outcome‐dependent observation times and informative censoring. Existing approaches commonly require a correct specification of the joint distribution of longitudinal measurements, the observation time process, and informative censoring time under the joint modeling framework and can be computationally cumbersome due to the complex form of the likelihood function. In view of these issues, we propose a semiparametric joint regression model and construct a composite likelihood function based on a conditional order statistics argument. As a major feature of our proposed methods, the aforementioned joint distribution is not required to be specified, and the random effect in the proposed joint model is treated as a nuisance parameter. Consequently, the derived composite likelihood bypasses the need to integrate over the random effect and offers the advantage of easy computation. We show that the resulting estimators are consistent and asymptotically normal. We use simulation studies to evaluate the finite‐sample performance of the proposed method and apply it to a study of weight loss data that motivated our investigation.     

Objective Bayesian Analysis of Skew‐t Distributions

Abstract. We study the Jeffreys prior and its properties for the shape parameter of univariate skew‐t distributions with linear and nonlinear Student's t skewing functions. In both cases, we show that the resulting priors for the shape parameter are symmetric around zero and proper. Moreover, we propose a Student's t approximation of the Jeffreys prior that makes an objective Bayesian analysis easy to perform. We carry out a Monte Carlo simulation study that demonstrates an overall better behaviour of the maximum a posteriori estimator compared with the maximum likelihood estimator. We also compare the frequentist coverage of the credible intervals based on the Jeffreys prior and its approximation and show that they are similar. We further discuss location‐scale models under scale mixtures of skew‐normal distributions and show some conditions for the existence of the posterior distribution and its moments. Finally, we present three numerical examples to illustrate the implications of our results on inference for skew‐t distributions.     

Evaluations of Bayesian and maximum likelihood methods in PK models with below‐quantification‐limit data

Pharmacokinetic (PK) data often contain concentration measurements below the quantification limit (BQL). While specific values cannot be assigned to these observations, nevertheless these observed BQL data are informative and generally known to be lower than the lower limit of quantification (LLQ). Setting BQLs as missing data violates the usual missing at random (MAR) assumption applied to the statistical methods, and therefore leads to biased or less precise parameter estimation. By definition, these data lie within the interval [0, LLQ], and can be considered as censored observations. Statistical methods that handle censored data, such as maximum likelihood and Bayesian methods, are thus useful in the modelling of such data sets. The main aim of this work was to investigate the impact of the amount of BQL observations on the bias and precision of parameter estimates in population PK models (non‐linear mixed effects models in general) under maximum likelihood method as implemented in SAS and NONMEM, and a Bayesian approach using Markov chain Monte Carlo (MCMC) as applied in WinBUGS. A second aim was to compare these different methods in dealing with BQL or censored data in a practical situation. The evaluation was illustrated by simulation based on a simple PK model, where a number of data sets were simulated from a one‐compartment first‐order elimination PK model. Several quantification limits were applied to each of the simulated data to generate data sets with certain amounts of BQL data. The average percentage of BQL ranged from 25% to 75%. Their influence on the bias and precision of all population PK model parameters such as clearance and volume distribution under each estimation approach was explored and compared. Copyright © 2009 John Wiley & Sons, Ltd.     

Regression analysis for a summed missing data problem under an outcome‐dependent sampling scheme

In this paper, we consider a regression analysis for a missing data problem in which the variables of primary interest are unobserved under a general biased sampling scheme, an outcome‐dependent sampling (ODS) design. We propose a semiparametric empirical likelihood method for accessing the association between a continuous outcome response and unobservable interesting factors. Simulation study results show that ODS design can produce more efficient estimators than the simple random design of the same sample size. We demonstrate the proposed approach with a data set from an environmental study for the genetic effects on human lung function in COPD smokers. The Canadian Journal of Statistics 40: 282–303; 2012 © 2012 Statistical Society of Canada     

General mixed‐data model: Extension of general location and grouped continuous models

The authors propose a general model for the joint distribution of nominal, ordinal and continuous variables. Their work is motivated by the treatment of various types of data. They show how to construct parameter estimates for their model, based on the maximization of the full likelihood. They provide algorithms to implement it, and present an alternative estimation method based on the pairwise likelihood approach. They also touch upon the issue of statistical inference. They illustrate their methodology using data from a foreign language achievement study.