Smooth random effects distribution in a linear mixed model

A linear mixed model with a smooth random effects density is proposed. A similar approach to P-spline smoothing of Eilers and Marx (1996, Statistical Science 11, 89-121) is applied to yield a more flexible estimate of the random effects density. Our approach differs from theirs in that the B-spline basis functions are replaced by approximating Gaussian densities. Fitting the model involves maximizing a penalized marginal likelihood. The best penalty parameters minimize Akaike's Information Criterion employing Gray's (1992, Journal of the American Statistical Association 87, 942-951) results. Although our method is applicable to any dimensions of the random effects structure, in this article the two-dimensional case is explored. Our methodology is conceptually simple, and it is relatively easy to fit in practice and is applied to the cholesterol data first analyzed by Zhang and Davidian (2001, Biometrics 57, 795-802). A simulation study shows that our approach yields almost unbiased estimates of the regression and the smoothing parameters in small sample settings. Consistency of the estimates is shown in a particular case.     

Fragment length distributions and collision probabilities for AFLP markers

AFLP is a DNA fingerprinting technique frequently used in plant and animal sciences. A drawback of the technique is the occurrence of multiple DNA fragments of the same length in a single AFLP lane, which we name a collision. In this article we quantify the problem. The well-known birthday problem plays a role. Calculation of collision probabilities requires a fragment length distribution (fld). We discuss three ways to estimate the fld: based on theoretical considerations, on in-silico determination using DNA sequence data from Arabidopsis thaliana, or on direct estimation from AFLP data. In the latter case we use a generalized linear model with monotone smoothing of the fragment length probabilities. Collision probabilities are calculated from two perspectives, assuming known fragment counts and assuming known band counts. We compare results for a number of fld's, ranging from uniform to highly skewed. The conclusion is that collisions occur often, with higher probabilities for higher numbers of bands, for more skewed distributions, and, to a lesser extent, for smaller scoring ranges. For a typical plant genome an AFLP with 19 bands is likely to contain the first collision. Practical implications of collisions are discussed. AFLP examples from lettuce and chicory are used for illustration.     

Structured additive regression for categorical space-time data: a mixed model approach

Motivated by a space-time study on forest health with damage state of trees as the response, we propose a general class of structured additive regression models for categorical responses, allowing for a flexible semiparametric predictor. Nonlinear effects of continuous covariates, time trends, and interactions between continuous covariates are modeled by penalized splines. Spatial effects can be estimated based on Markov random fields, Gaussian random fields, or two-dimensional penalized splines. We present our approach from a Bayesian perspective, with inference based on a categorical linear mixed model representation. The resulting empirical Bayes method is closely related to penalized likelihood estimation in a frequentist setting. Variance components, corresponding to inverse smoothing parameters, are estimated using (approximate) restricted maximum likelihood. In simulation studies we investigate the performance of different choices for the spatial effect, compare the empirical Bayes approach to competing methodology, and study the bias of mixed model estimates. As an application we analyze data from the forest health survey.     

An approximate Bayesian approach for estimation of the instantaneous reproduction number under misreported epidemic data

In epidemic models, the effective reproduction number is of central importance to assess the transmission dynamics of an infectious disease and to orient health intervention strategies. Publicly shared data during an outbreak often suffers from two sources of misreporting (underreporting and delay in reporting) that should not be overlooked when estimating epidemiological parameters. The main statistical challenge in models that intrinsically account for a misreporting process lies in the joint estimation of the time-varying reproduction number and the delay/underreporting parameters. Existing Bayesian approaches typically rely on Markov chain Monte Carlo algorithms that are extremely costly from a computational perspective. We propose a much faster alternative based on Laplacian-P-splines (LPS) that combines Bayesian penalized B-splines for flexible and smooth estimation of the instantaneous reproduction number and Laplace approximations to selected posterior distributions for fast computation. Assuming a known generation interval distribution, the incidence at a given calendar time is governed by the epidemic renewal equation and the delay structure is specified through a composite link framework. Laplace approximations to the conditional posterior of the spline vector are obtained from analytical versions of the gradient and Hessian of the log-likelihood, implying a drastic speed-up in the computation of posterior estimates. Furthermore, the proposed LPS approach can be used to obtain point estimates and approximate credible intervals for the delay and reporting probabilities. Simulation of epidemics with different combinations for the underreporting rate and delay structure (one-day, two-day, and weekend delays) show that the proposed LPS methodology delivers fast and accurate estimates outperforming existing methods that do not take into account underreporting and delay patterns. Finally, LPS is illustrated in two real case studies of epidemic outbreaks.     

A Bayesian Nonparametric Approach for Mapping Dynamic Quantitative Traits

In biology, many quantitative traits are dynamic in nature. They can often be described by some smooth functions or curves. A joint analysis of all the repeated measurements of the dynamic traits by functional quantitative trait loci (QTL) mapping methods has the benefits to (1) understand the genetic control of the whole dynamic process of the quantitative traits and (2) improve the statistical power to detect QTL. One crucial issue in functional QTL mapping is how to correctly describe the smoothness of trajectories of functional valued traits. We develop an efficient Bayesian nonparametric multiple-loci procedure for mapping dynamic traits. The method uses the Bayesian P-splines with (nonparametric) B-spline bases to specify the functional form of a QTL trajectory and a random walk prior to automatically determine its degree of smoothness. An efficient deterministic variational Bayes algorithm is used to implement both (1) the search of an optimal subset of QTL among large marker panels and (2) estimation of the genetic effects of the selected QTL changing over time. Our method can be fast even on some large-scale data sets. The advantages of our method are illustrated on both simulated and real data sets.     

Variable selection with P-splines in functional linear regression: Application in graft-versus-host disease

This paper focuses on the problems of estimation and variable selection in the functional linear regression model (FLM) with functional response and scalar covariates. To this end, two different types of regularization (L₁ and L₂) are considered in this paper. On the one hand, a sample approach for functional LASSO in terms of basis representation of the sample values of the response variable is proposed. On the other hand, we propose a penalized version of the FLM by introducing a P-spline penalty in the least squares fitting criterion. But our aim is to propose P-splines as a powerful tool simultaneously for variable selection and functional parameters estimation. In that sense, the importance of smoothing the response variable before fitting the model is also studied. In summary, penalized (L₁ and L₂) and nonpenalized regression are combined with a presmoothing of the response variable sample curves, based on regression splines or P-splines, providing a total of six approaches to be compared in two simulation schemes. Finally, the most competitive approach is applied to a real data set based on the graft-versus-host disease, which is one of the most frequent complications (30% –50%) in allogeneic hematopoietic stem-cell transplantation.