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Matrix models for childhood infections: a Bayesian approach with applications to rubella and mumps.

Mathematical modelling is an established tool for planning and monitoring vaccination programmes. However, the matrices describing contact rates are based on subjective choices, which have a large impact on results. This paper reviews published models and obtains prior model probabilities based on publication frequency and expert opinion. Using serological survey data on rubella and mumps, Bayesian methods of model choice are applied to select the most plausible models. Estimates of the basic reproduction number R0 are derived, taking into account model uncertainty and individual heterogeneity in contact rates. Twenty-two models are documented, for which publication frequency and expert opinion are negatively correlated. Using the expert prior with individual heterogeneity, R0=6.1 [95% credible region (CR) 4.3-9.2] for rubella and R0=19.3 (95% CR 4.0-31.5) for mumps. The posterior modes are insensitive to the prior for rubella but not for mumps. Overall, assortative models with individual heterogeneity are recommended.

Bayes Theorem↗

Bayesian population dynamics of interacting species: great gerbils and fleas in Kazakhstan.

We propose a discrete-time Bayesian hierarchical model for the population dynamics of the great gerbil-flea ecological system. The model accounts for the sampling variability arising from data originally collected for other purposes. The prior for the unknown population densities incorporates specific biological hypotheses regarding the interacting dynamics of the two species, as well as their life cycles, where density-dependent effects are included. Posterior estimates are obtained via Markov chain Monte Carlo. The variance of the observed density estimates is a quadratic function of the unknown density. Our study indicates the presence of a density-dependent growth rate for the gerbil population. For the flea population there is clear evidence of density-dependent over-summer net growth, which is dependent on the flea-to-gerbil ratio at the beginning of the reproductive summer. Over-winter net growth is favored by high density. We estimate that on average 35% of the gerbil population survives the winter. Our study shows that hierarchical Bayesian models can be useful in extracting ecobiological information from observational data.

Animals↗

Bayesian methods for quantitative trait loci mapping based on model selection: approximate analysis using the Bayesian information criterion.

We describe an approximate method for the analysis of quantitative trait loci (QTL) based on model selection from multiple regression models with trait values regressed on marker genotypes, using a modification of the easily calculated Bayesian information criterion to estimate the posterior probability of models with various subsets of markers as variables. The BIC-delta criterion, with the parameter delta increasing the penalty for additional variables in a model, is further modified to incorporate prior information, and missing values are handled by multiple imputation. Marginal probabilities for model sizes are calculated, and the posterior probability of nonzero model size is interpreted as the posterior probability of existence of a QTL linked to one or more markers. The method is demonstrated on analysis of associations between wood density and markers on two linkage groups in Pinus radiata. Selection bias, which is the bias that results from using the same data to both select the variables in a model and estimate the coefficients, is shown to be a problem for commonly used non-Bayesian methods for QTL mapping, which do not average over alternative possible models that are consistent with the data.

Alleles↗

Bayesian identification of a population compartmental model of C-peptide kinetics.

When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368-377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment.

Adult↗

A Bayesian network driven approach to model the transcriptional response to nitric oxide in Saccharomyces cerevisiae.

The transcriptional response to exogenously supplied nitric oxide in Saccharomyces cerevisiae was modeled using an integrated framework of Bayesian network learning and experimental feedback. A Bayesian network learning algorithm was used to generate network models of transcriptional output, followed by model verification and revision through experimentation. Using this framework, we generated a network model of the yeast transcriptional response to nitric oxide and a panel of other environmental signals. We discovered two environmental triggers, the diauxic shift and glucose repression, that affected the observed transcriptional profile. The computational method predicted the transcriptional control of yeast flavohemoglobin YHB1 by glucose repression, which was subsequently experimentally verified. A freely available software application, ExpressionNet, was developed to derive Bayesian network models from a combination of gene expression profile clusters, genetic information and experimental conditions.

Algorithms↗

Genome-wide association studies for feed efficiency, production and feeding behavior traits in Canadian purebred Duroc pigs.

This study aimed to identify potential genetic variants and candidate genes associated with feed efficiency (FE), production, and feeding behavior traits in Canadian purebred Duroc pigs. Genome-wide association studies (GWAS) were conducted using 8,861 individuals and an imputed Affymetrix PigGen Canada 50K panel v2.0 using a linear mixed model (LMM) and a Bayesian B model. This analysis used an adjusted P-value threshold (ranging from 6.6 × 10-5 to 1.3 × 10-4) using a false-discovery rate to determine significance. The number of significant SNPs identified for each trait was as follows: average daily gain (ADG, 48), daily feed intake (DFI, 85), feed conversion ratio (FCR, 101), residual feed intake (RFI, 37), residual gain (RG, 64), residual intake and gain (RIG, 55), backfat thickness (BF, 100), loin depth (LD, 6), Kleiber's ratio (KR, 0), total time spent eating per day (TPD, 7), and number of visits to the feeder per day (NVD, 6). Several traits (BF, DFI, FCR, RFI, RG, and RIG) showed strong overlapping signals on chromosomes 7 and 10 with 24 shared significant SNPs, indicating potential shared genetic mechanisms. These traits also had 71 overlapping candidate genes, such as PACSIN1, PTCH1, ADIPOR1, and ITPR3, associated with glucose, lipid, and cholesterol metabolism. Well-known candidate genes in literature associated with growth and fatness such as MC4R and CDH20 were also identified to be associated with ADG, BF, FCR, and DFI in this study. Gene ontology enrichment analysis revealed that a set of the candidate genes were involved in the gonadotropin-releasing hormone (GnRH) and the platelet-derived growth factor (PDGF) signaling pathways. Overall, this study contributed to understanding the genetic architecture and provided a biological foundation for improving FE, production, and feeding behavior traits in Canadian Duroc pigs, facilitating the selection of more efficient pigs.

Sus scrofa↗

Linear Bayesian inference for accelerated Weibull model.

In this paper, we present a Bayesian approach for inference from accelerated life tests when the underlying life model is Weibull. Our approach is based on the General Linear Models framework of West, Harrison and Migon (1985). We discuss inference for the model and show that computable results can be obtained using linear Bayesian methods. We illustrate the usefulness of our approach by applying it to some actual data from accelerated life tests.

Bayes Theorem↗

BYY harmony learning, structural RPCL, and topological self-organizing on mixture models.

The Bayesian Ying-Yang (BYY) harmony learning acts as a general statistical learning framework, featured by not only new regularization techniques for parameter learning but also a new mechanism that implements model selection either automatically during parameter learning or via a new class of model selection criteria used after parameter learning. In this paper, further advances on BYY harmony learning by considering modular inner representations are presented in three parts. One consists of results on unsupervisedmixture models, ranging from Gaussian mixture based Mean Square Error (MSE) clustering, elliptic clustering, subspace clustering to NonGaussian mixture based clustering not only with each cluster represented via either Bernoulli-Gaussian mixtures or independent real factor models, but also with independent component analysis implicitly made on each cluster. The second consists of results on supervised mixture-of-experts (ME) models, including Gaussian ME, Radial Basis Function nets, and Kernel regressions. The third consists of two strategies for extending the above structural mixtures into self-organized topological maps. All these advances are introduced with details on three issues, namely, (a) adaptive learning algorithms, especially elliptic, subspace, and structural rival penalized competitive learning algorithms, with model selection made automatically during learning; (b) model selection criteria for being used after parameter learning, and (c) how these learning algorithms and criteria are obtained from typical special cases of BYY harmony learning.

Bayes Theorem↗

A semiparametric Bayesian approach to the random effects model.

In longitudinal random effects models, the random effects are typically assumed to have a normal distribution in both Bayesian and classical models. We provide a Bayesian model that allows the random effects to have a nonparametric prior distribution. We propose a Dirichlet process prior for the distribution of the random effects; computation is made possible by the Gibbs sampler. An example using marker data from an AIDS study is given to illustrate the methodology.

Acquired Immunodeficiency Syndrome↗

Multiple imputation under Bayesianly smoothed pattern-mixture models for non-ignorable drop-out.

Conventional pattern-mixture models can be highly sensitive to model misspecification. In many longitudinal studies, where the nature of the drop-out and the form of the population model are unknown, interval estimates from any single pattern-mixture model may suffer from undercoverage, because uncertainty about model misspecification is not taken into account. In this article, a new class of Bayesian random coefficient pattern-mixture models is developed to address potentially non-ignorable drop-out. Instead of imposing hard equality constraints to overcome inherent inestimability problems in pattern-mixture models, we propose to smooth the polynomial coefficient estimates across patterns using a hierarchical Bayesian model that allows random variation across groups. Using real and simulated data, we show that multiple imputation under a three-level linear mixed-effects model which accommodates a random level due to drop-out groups can be an effective method to deal with non-ignorable drop-out by allowing model uncertainty to be incorporated into the imputation process.

Antipsychotic Agents↗

Bayesian analysis for generalized linear models with nonignorably missing covariates.

We propose Bayesian methods for estimating parameters in generalized linear models (GLMs) with nonignorably missing covariate data. We show that when improper uniform priors are used for the regression coefficients, phi, of the multinomial selection model for the missing data mechanism, the resulting joint posterior will always be improper if (i) all missing covariates are discrete and an intercept is included in the selection model for the missing data mechanism, or (ii) at least one of the covariates is continuous and unbounded. This impropriety will result regardless of whether proper or improper priors are specified for the regression parameters, beta, of the GLM or the parameters, alpha, of the covariate distribution. To overcome this problem, we propose a novel class of proper priors for the regression coefficients, phi, in the selection model for the missing data mechanism. These priors are robust and computationally attractive in the sense that inferences about beta are not sensitive to the choice of the hyperparameters of the prior for phi and they facilitate a Gibbs sampling scheme that leads to accelerated convergence. In addition, we extend the model assessment criterion of Chen, Dey, and Ibrahim (2004a, Biometrika 91, 45-63), called the weighted L measure, to GLMs and missing data problems as well as extend the deviance information criterion (DIC) of Spiegelhalter et al. (2002, Journal of the Royal Statistical Society B 64, 583-639) for assessing whether the missing data mechanism is ignorable or nonignorable. A novel Markov chain Monte Carlo sampling algorithm is also developed for carrying out posterior computation. Several simulations are given to investigate the performance of the proposed Bayesian criteria as well as the sensitivity of the prior specification. Real datasets from a melanoma cancer clinical trial and a liver cancer study are presented to further illustrate the proposed methods.

Bayes Theorem↗

Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response modeling in mice.

The current USEPA cancer risk assessment for dichloromethane (DCM) is based on deterministic physiologically based pharmacokinetic (PBPK) modeling involving comparative metabolism of DCM by the GST pathway in the lung and liver of humans and mice. Recent advances in PBPK modeling include probabilistic methods and, in particular, Bayesian inference to quantitatively address variability and uncertainty separately. Although Bayesian analysis of human PBPK models has been published, no such efforts have been reported specifically addressing the mouse, apart from results included in the OSHA final rule on DCM. Certain aspects of the OSHA model, however, are not consistent with current approaches or with the USEPA's current DCM cancer risk assessment. Therefore, Bayesian analysis of the mouse PBPK model and dose-response modeling was undertaken to support development of an improved cancer risk assessment for DCM. A hierarchical population model was developed and prior parameter distributions were selected to reflect parameter values that were considered the most appropriate and best available. Bayesian modeling was conducted using MCSim, a publicly available software program for Markov Chain Monte Carlo analysis. Mean posterior values from the calibrated model were used to develop internal dose metrics, i.e., mg DCM metabolized by the GST pathway/L tissue/day in the lung and liver using exposure concentrations and results from the NTP mouse bioassay, consistent with the approach used by the USEPA for its current DCM cancer risk assessment. Internal dose metrics were 3- to 4-fold higher than those that support the current USEPA IRIS assessment. A decrease of similar magnitude was also noted in dose-response modeling results. These results show that the Bayesian PBPK model in the mouse provides an improved basis for a cancer risk assessment of DCM.

Animals↗

Bayesian comparison of spatially regularised general linear models.

In previous work (Penny et al., [2005]: Neuroimage 24:350-362) we have developed a spatially regularised General Linear Model for the analysis of functional magnetic resonance imaging data that allows for the characterisation of regionally specific effects using Posterior Probability Maps (PPMs). In this paper we show how it also provides an approximation to the model evidence. This is important as it is the basis of Bayesian model comparison and provides a unified framework for Bayesian Analysis of Variance, Cluster of Interest analyses and the principled selection of signal and noise models. We also provide extensions that implement spatial and anatomical regularisation of noise process parameters.

Artifacts↗

A Bayesian analysis of regression models with continuous errors with application to longitudinal studies.

We employ a regression model with errors that follow a continuous autoregressive process to analyse longitudinal studies. In this way, unequally spaced observations do not present a problem in the analysis. We employ a Bayesian approach, where our inferences are based on a direct resampling process that generates values from the posterior distribution of the parameters of the model. We illustrate these Bayesian inferences with an analysis of a longitudinal study that involves the regression of foetal head circumference on menstrual age. Using these same data, we contrast the Bayesian approach with a maximum likelihood technique.

Bayes Theorem↗

VOMBAT: prediction of transcription factor binding sites using variable order Bayesian trees.

Variable order Markov models and variable order Bayesian trees have been proposed for the recognition of transcription factor binding sites, and it could be demonstrated that they outperform traditional models, such as position weight matrices, Markov models and Bayesian trees. We develop a web server for the recognition of DNA binding sites based on variable order Markov models and variable order Bayesian trees offering the following functionality: (i) given datasets with annotated binding sites and genomic background sequences, variable order Markov models and variable order Bayesian trees can be trained; (ii) given a set of trained models, putative DNA binding sites can be predicted in a given set of genomic sequences and (iii) given a dataset with annotated binding sites and a dataset with genomic background sequences, cross-validation experiments for different model combinations with different parameter settings can be performed. Several of the offered services are computationally demanding, such as genome-wide predictions of DNA binding sites in mammalian genomes or sets of 10(4)-fold cross-validation experiments for different model combinations based on problem-specific data sets. In order to execute these jobs, and in order to serve multiple users at the same time, the web server is attached to a Linux cluster with 150 processors. VOMBAT is available at http://pdw-24.ipk-gatersleben.de:8080/VOMBAT/.

Algorithms↗

A Bayesian approach to jointly modeling toxicity and biomarker expression in a phase I/II dose-finding trial.

In this article, we propose a Bayesian approach to phase I/II dose-finding oncology trials by jointly modeling a binary toxicity outcome and a continuous biomarker expression outcome. We apply our method to a clinical trial of a new gene therapy for bladder cancer patients. In this trial, the biomarker expression indicates biological activity of the new therapy. For ethical reasons, the trial is conducted sequentially, with the dose for each successive patient chosen using both toxicity and activity data from patients previously treated in the trial. The modeling framework that we use naturally incorporates correlation between the binary toxicity and continuous activity outcome via a latent Gaussian variable. The dose-escalation/de-escalation decision rules are based on the posterior distributions of both toxicity and activity. A flexible state-space model is used to relate the activity outcome and dose. Extensive simulation studies show that the design reliably chooses the preferred dose using both toxicity and expression outcomes under various clinical scenarios.

Algorithms↗

Bayesian non-response models for categorical data from small areas: an application to BMD and age.

We provide a Bayesian analysis of data categorized into two levels of age (younger than 50 years, at least 50 years) and three levels of bone mineral density (normal, osteopenia, osteoporosis) for white females at least 20 years old in the third National Health and Nutrition Examination Survey. For the sample, the age of each individual is known, but some individuals did not have their BMD measured. We use two types of models: In the ignorable non-response models the propensity to respond does not depend on BMD and age of an individual, while in the non-ignorable non-response models it does. These are the baseline models which are used to derive all models for testing. Our non-ignorable non-response models are 'close' to the ignorable non-response models, thereby reducing the effects of the assumptions about non-respondents that cannot be tested in non-response models. We have data from 35 counties, small areas, and therefore our models are hierarchical, a feature that allows a 'borrowing of strength' across the counties, and they provide a substantial reduction in variation. The non-ignorable non-response models are generalizations of the ignorable non-response models, and therefore, the non-ignorable non-response models allow broader inference. The joint posterior density of the parameters for each model is complex, and therefore, we fit each model using Markov chain Monte Carlo methods to obtain samples which are used to make inference about BMD and age. For each county we can estimate the proportion of individuals in each BMD and age cell of the categorical table, and we can assess the relation between BMD and age using the Bayes factor. A sensitivity analysis shows that there are differences (typically small) in inference that permits different levels of association between BMD and age. A simulation study shows that there is not much difference between the baseline ignorable and non-ignorable non-response models.

Adult↗

A Monte Carlo method for Bayesian inference in frailty models.

Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties." Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods.

Algorithms↗