Model‐based clustering of longitudinal data

A new family of mixture models for the model‐based clustering of longitudinal data is introduced. The covariance structures of eight members of this new family of models are given and the associated maximum likelihood estimates for the parameters are derived via expectation–maximization (EM) algorithms. The Bayesian information criterion is used for model selection and a convergence criterion based on the Aitken acceleration is used to determine the convergence of these EM algorithms. This new family of models is applied to yeast sporulation time course data, where the models give good clustering performance. Further constraints are then imposed on the decomposition to allow a deeper investigation of the correlation structure of the yeast data. These constraints greatly extend this new family of models, with the addition of many parsimonious models. The Canadian Journal of Statistics 38:153–168; 2010 © 2010 Statistical Society of Canada     

Functional approach of flexibly modelling generalized longitudinal data and survival time

We propose a flexible functional approach for modelling generalized longitudinal data and survival time using principal components. In the proposed model the longitudinal observations can be continuous or categorical data, such as Gaussian, binomial or Poisson outcomes. We generalize the traditional joint models that treat categorical data as continuous data by using some transformations, such as CD4 counts. The proposed model is data-adaptive, which does not require pre-specified functional forms for longitudinal trajectories and automatically detects characteristic patterns. The longitudinal trajectories observed with measurement error or random error are represented by flexible basis functions through a possibly nonlinear link function, combining dimension reduction techniques resulting from functional principal component (FPC) analysis. The relationship between the longitudinal process and event history is assessed using a Cox regression model. Although the proposed model inherits the flexibility of non-parametric methods, the estimation procedure based on the EM algorithm is still parametric in computation, and thus simple and easy to implement. The computation is simplified by dimension reduction for random coefficients or FPC scores. An iterative selection procedure based on Akaike information criterion (AIC) is proposed to choose the tuning parameters, such as the knots of spline basis and the number of FPCs, so that appropriate degree of smoothness and fluctuation can be addressed. The effectiveness of the proposed approach is illustrated through a simulation study, followed by an application to longitudinal CD4 counts and survival data which were collected in a recent clinical trial to compare the efficiency and safety of two antiretroviral drugs.     

Likelihood-Based Inference for Multivariate Skew-Normal Regression Models

In this article, we present EM algorithms for performing maximum likelihood estimation for three multivariate skew-normal regression models of considerable practical interest. We also consider the restricted estimation of the parameters of certain important special cases of two models. The methodology developed is applied in the analysis of longitudinal data on dental plaque and cholesterol levels.     

A multivariate finite mixture latent trajectory model with application to dementia studies

Dementia patients exhibit considerable heterogeneity in individual trajectories of cognitive decline, with some patients showing rapid decline following diagnoses while others exhibiting slower decline or remaining stable for several years. Dementia studies often collect longitudinal measures of multiple neuropsychological tests aimed to measure patients’ decline across a number of cognitive domains. We propose a multivariate finite mixture latent trajectory model to identify distinct longitudinal patterns of cognitive decline simultaneously in multiple cognitive domains, each of which is measured by multiple neuropsychological tests. EM algorithm is used for parameter estimation and posterior probabilities are used to predict latent class membership. We present results of a simulation study demonstrating adequate performance of our proposed approach and apply our model to the Uniform Data Set from the National Alzheimer's Coordinating Center to identify cognitive decline patterns among dementia patients.     

Inference methods for saturated models in longitudinal clinical trials with incomplete binary data

In the longitudinal studies with binary response, it is often of interest to estimate the percentage of positive responses at each time point and the percentage of having at least one positive response by each time point. When missing data exist, the conventional method based on observed percentages could result in erroneous estimates. This study demonstrates two methods of using expectation-maximization (EM) and data augmentation (DA) algorithms in the estimation of the marginal and cumulative probabilities for incomplete longitudinal binary response data. Both methods provide unbiased estimates when the missingness mechanism is missing at random (MAR) assumption. Sensitivity analyses have been performed for cases when the MAR assumption is in question.     

Mini-batch learning of exponential family finite mixture models

Mini-batch algorithms have become increasingly popular due to the requirement for solving optimization problems, based on large-scale data sets. Using an existing online expectation–maximization (EM) algorithm framework, we demonstrate how mini-batch (MB) algorithms may be constructed, and propose a scheme for the stochastic stabilization of the constructed mini-batch algorithms. Theoretical results regarding the convergence of the mini-batch EM algorithms are presented. We then demonstrate how the mini-batch framework may be applied to conduct maximum likelihood (ML) estimation of mixtures of exponential family distributions, with emphasis on ML estimation for mixtures of normal distributions. Via a simulation study, we demonstrate that the mini-batch algorithm for mixtures of normal distributions can outperform the standard EM algorithm. Further evidence of the performance of the mini-batch framework is provided via an application to the famous MNIST data set.     

Acceleration of Expectation-Maximization algorithm for length-biased right-censored data

Vardi’s Expectation-Maximization (EM) algorithm is frequently used for computing the nonparametric maximum likelihood estimator of length-biased right-censored data, which does not admit a closed-form representation. The EM algorithm may converge slowly, particularly for heavily censored data. We studied two algorithms for accelerating the convergence of the EM algorithm, based on iterative convex minorant and Aitken’s delta squared process. Numerical simulations demonstrate that the acceleration algorithms converge more rapidly than the EM algorithm in terms of number of iterations and actual timing. The acceleration method based on a modification of Aitken’s delta squared performed the best under a variety of settings.     

A new REML (parameter expanded) EM algorithm for linear mixed models

Linear mixed models are regularly applied to animal and plant breeding data to evaluate genetic potential. Residual maximum likelihood (REML) is the preferred method for estimating variance parameters associated with this type of model. Typically an iterative algorithm is required for the estimation of variance parameters. Two algorithms which can be used for this purpose are the expectation‐maximisation (EM) algorithm and the parameter expanded EM (PX‐EM) algorithm. Both, particularly the EM algorithm, can be slow to converge when compared to a Newton‐Raphson type scheme such as the average information (AI) algorithm. The EM and PX‐EM algorithms require specification of the complete data, including the incomplete and missing data. We consider a new incomplete data specification based on a conditional derivation of REML. We illustrate the use of the resulting new algorithm through two examples: a sire model for lamb weight data and a balanced incomplete block soybean variety trial. In the cases where the AI algorithm failed, a REML PX‐EM based on the new incomplete data specification converged in 28% to 30% fewer iterations than the alternative REML PX‐EM specification. For the soybean example a REML EM algorithm using the new specification converged in fewer iterations than the current standard specification of a REML PX‐EM algorithm. The new specification integrates linear mixed models, Henderson's mixed model equations, REML and the REML EM algorithm into a cohesive framework.     

Fitting mixtures of linear regressions

In most applications, the parameters of a mixture of linear regression models are estimated by maximum likelihood using the expectation maximization (EM) algorithm. In this article, we propose the comparison of three algorithms to compute maximum likelihood estimates of the parameters of these models: the EM algorithm, the classification EM algorithm and the stochastic EM algorithm. The comparison of the three procedures was done through a simulation study of the performance (computational effort, statistical properties of estimators and goodness of fit) of these approaches on simulated data sets.

Simulation results show that the choice of the approach depends essentially on the configuration of the true regression lines and the initialization of the algorithms.     

The EM algorithm with gradient function update for discrete mixtures with known (fixed) number of components

The paper is focussing on some recent developments in nonparametric mixture distributions. It discusses nonparametric maximum likelihood estimation of the mixing distribution and will emphasize gradient type results, especially in terms of global results and global convergence of algorithms such as vertex direction or vertex exchange method. However, the NPMLE (or the algorithms constructing it) provides also an estimate of the number of components of the mixing distribution which might be not desirable for theoretical reasons or might be not allowed from the physical interpretation of the mixture model. When the number of components is fixed in advance, the before mentioned algorithms can not be used and globally convergent algorithms do not exist up to now. Instead, the EM algorithm is often used to find maximum likelihood estimates. However, in this case multiple maxima are often occuring. An example from a meta-analyis of vitamin A and childhood mortality is used to illustrate the considerable, inferential importance of identifying the correct global likelihood. To improve the behavior of the EM algorithm we suggest a combination of gradient function steps and EM steps to achieve global convergence leading to the EM algorithm with gradient function update (EMGFU). This algorithms retains the number of components to be exactly k and typically converges to the global maximum. The behavior of the algorithm is highlighted at hand of several examples.     

Combinatorial EM algorithms

The complete-data model that underlies an Expectation-Maximization (EM) algorithm must have a parameter space that coincides with the parameter space of the observed-data model. Otherwise, maximization of the observed-data log-likelihood will be carried out over a space that does not coincide with the desired parameter space. In some contexts, however, a natural complete-data model may be defined only for parameter values within a subset of the observed-data parameter space. In this paper we discuss situations where this can still be useful if the complete-data model can be viewed as a member of a finite family of complete-data models that have parameter spaces which collectively cover the observed-data parameter space. Such a family of complete-data models defines a family of EM algorithms which together lead to a finite collection of constrained maxima of the observed-data log-likelihood. Maximization of the log-likelihood function over the full parameter space then involves identifying the constrained maximum that achieves the greatest log-likelihood value. Since optimization over a finite collection of candidates is referred to as combinatorial optimization, we refer to such a family of EM algorithms as a combinatorial EM (CEM) algorithm. As well as discussing the theoretical concepts behind CEM algorithms, we discuss strategies for improving the computational efficiency when the number of complete-data models is large. Various applications of CEM algorithms are also discussed, ranging from simple examples that illustrate the concepts, to more substantive examples that demonstrate the usefulness of CEM algorithms in practice.     

Initializing EM using the properties of its trajectories in Gaussian mixtures

A strategy is proposed to initialize the EM algorithm in the multivariate Gaussian mixture context. It consists in randomly drawing, with a low computational cost in many situations, initial mixture parameters in an appropriate space including all possible EM trajectories. This space is simply defined by two relations between the two first empirical moments and the mixture parameters satisfied by any EM iteration. An experimental study on simulated and real data sets clearly shows that this strategy outperforms classical methods, since it has the nice property to widely explore local maxima of the likelihood function.     

Bayesian clustering for continuous-time hidden Markov models

We develop clustering procedures for longitudinal trajectories based on a continuous-time hidden Markov model (CTHMM) and a generalized linear observation model. Specifically, in this article we carry out finite and infinite mixture model-based clustering for a CTHMM and achieve inference using Markov chain Monte Carlo (MCMC). For a finite mixture model with a prior on the number of components, we implement reversible-jump MCMC to facilitate the trans-dimensional move between models with different numbers of clusters. For a Dirichlet process mixture model, we utilize restricted Gibbs sampling split–merge proposals to improve the performance of the MCMC algorithm. We apply our proposed algorithms to simulated data as well as a real-data example, and the results demonstrate the desired performance of the new sampler.     

Standard errors for EM estimation

The EM algorithm is a popular method for computing maximum likelihood estimates. One of its drawbacks is that it does not produce standard errors as a by-product. We consider obtaining standard errors by numerical differentiation. Two approaches are considered. The first differentiates the Fisher score vector to yield the Hessian of the log-likelihood. The second differentiates the EM operator and uses an identity that relates its derivative to the Hessian of the log-likelihood. The well-known SEM algorithm uses the second approach. We consider three additional algorithms: one that uses the first approach and two that use the second. We evaluate the complexity and precision of these three and the SEM in algorithm seven examples. The first is a single-parameter example used to give insight. The others are three examples in each of two areas of EM application: Poisson mixture models and the estimation of covariance from incomplete data. The examples show that there are algorithms that are much simpler and more accurate than the SEM algorithm. Hopefully their simplicity will increase the availability of standard error estimates in EM applications. It is shown that, as previously conjectured, a symmetry diagnostic can accurately estimate errors arising from numerical differentiation. Some issues related to the speed of the EM algorithm and algorithms that differentiate the EM operator are identified.     

The performance of standard and hybrid em algorithms for ml estimates of the normal mixture model with censoring

Many studies have been made of the performance of standard algorithms used to estimate the parameters of a mixture density, where data arise from two or more underlying populations. While these studies examine uncensored data, many mixture processes are right-censored. Therefore, this paper addresses the accuracy and efficiency of standard and hybrid algorithms under different degrees of right-censored data. While a common belief is that the EM algorithm is slow and inaccurate, we find that the EM generally exhibits excellent efficiency and accuracy. While extreme right censoring causes the EM to frequently fail to converge, a hybrid-EM algorithm is found to be superior at all levels of right-censoring.s     

Stochastic approximation Monte Carlo EM for change-point analysis

In the expectation–maximization (EM) algorithm for maximum likelihood estimation from incomplete data, Markov chain Monte Carlo (MCMC) methods have been used in change-point inference for a long time when the expectation step is intractable. However, the conventional MCMC algorithms tend to get trapped in local mode in simulating from the posterior distribution of change points. To overcome this problem, in this paper we propose a stochastic approximation Monte Carlo version of EM (SAMCEM), which is a combination of adaptive Markov chain Monte Carlo and EM utilizing a maximum likelihood method. SAMCEM is compared with the stochastic approximation version of EM and reversible jump Markov chain Monte Carlo version of EM on simulated and real datasets. The numerical results indicate that SAMCEM can outperform among the three methods by producing much more accurate parameter estimates and the ability to achieve change-point positions and estimates simultaneously.     

Efficient estimation for incomplete multivariate data

We review the Fisher scoring and EM algorithms for incomplete multivariate data from an estimating function point of view, and examine the corresponding quasi-score functions under second-moment assumptions. A bias-corrected REML-type estimator for the covariance matrix is derived, and the Fisher, Godambe and empirical sandwich information matrices are compared. We make a numerical investigation of the two algorithms, and compare with a hybrid algorithm, where Fisher scoring is used for the mean vector and the EM algorithm for the covariance matrix.     

Likelihood-Based Inference in Autoregressive Models with Scaled t-Distributed Innovations by Means of EM-Based Algorithms

This article applies the EM-based (ECM and ECME) algorithms to find the maximum likelihood estimates of model parameters in general AR models with independent scaled t-distributed innovations whenever the degrees of freedom are unknown. The ECME, sharing advantages with both EM and Newton–Raphson algorithms, is an extension of ECM, which itself is an extension of the EM algorithm. The ECM and ECME algorithms, which are analytically quite simple to use, are then compared based on the computational running time and the accuracy of estimation via a simulation study. The results demonstrate that the ECME is efficient and usable in practice. We also show how our method can be applied to the Wolfer's sunspot data.     

Quantile Regression via the EM Algorithm

The three-parameter asymmetric Laplace distribution (ALD) has received increasing attention in the field of quantile regression due to an important feature between its location and asymmetric parameters. On the basis of the representation of the ALD as a normal-variance–mean mixture with an exponential mixing distribution, this article develops EM and generalized EM algorithms, respectively, for computing regression quantiles of linear and nonlinear regression models. It is interesting to show that the proposed EM algorithm and the MM (Majorization–Minimization) algorithm for quantile regressions are really the same in terms of computation, since the updating formula of them are the same. This provides a good example that connects the EM and MM algorithms. Simulation studies show that the EM algorithm can successfully recover the true parameters in quantile regressions.     

Least absolute deviations estimation via the EM algorithm

This paper derives EM and generalized EM (GEM) algorithms for calculating least absolute deviations (LAD) estimates of the parameters of linear and nonlinear regression models. It shows that Schlossmacher's iterative reweighted least squares algorithm for calculating LAD estimates (E.J. Schlossmacher, Journal of the American Statistical Association 68: 857–859, 1973) is an EM algorithm. A GEM algorithm for computing LAD estimates of the parameters of nonlinear regression models is also provided and is applied in some examples.