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At least 1,279 records · Page 71Linked to original sources
PubMed2006

A framework of integrating gene relations from heterogeneous data sources: an experiment on Arabidopsis thaliana.

One of the most important goals of biological investigation is to uncover gene functional relations. In this study we propose a framework for extraction and integration of gene functional relations from diverse biological data sources, including gene expression data, biological literature and genomic sequence information. We introduce a two-layered Bayesian network approach to integrate relations from multiple sources into a genome-wide functional network. An experimental study was conducted on a test-bed of Arabidopsis thaliana. Evaluation of the integrated network demonstrated that relation integration could improve the reliability of relations by combining evidence from different data sources. Domain expert judgments on the gene functional clusters in the network confirmed the validity of our approach for relation integration and network inference.

Arabidopsis↗
PubMed2006

Ensembles of Bayesian-regularized genetic neural networks for modeling of acetylcholinesterase inhibition by huprines.

Acetylcholinesterase inhibition was modeled for a set of huprines using ensembles of Bayesian-regularized Genetic Neural Networks. In the Bayesian-regularized Genetic Neural Network approach the Bayesian regularization avoids overfitted regressions and the genetic algorithm allows exploring a wide pool of three-dimensional descriptors. The predictive capacity of our selected model was evaluated by averaging multiple validation sets generated as members of neural network ensembles. When 60 members are assembled, the neural network ensemble provides a reliable measure of training and test set R(2)-values of 0.945 and 0.850 respectively. In other respects, the ability of the nonlinear selected genetic algorithm space for differentiate the data were evidenced when total data set was well distributed in a Kohonen self-organizing map. The analysis of the self-organizing map zones allows establishing the main structural features differentiated by our vectorial space.

Acetylcholinesterase↗
PubMed1996

A comparison of a Bayesian population method with two methods as implemented in commercially available software.

In this paper we describe and discuss three specific estimation procedures that are available within commercially available population software packages. The first version of NONMEM (l) was released in 1979 and later versions are the standard analysis tools in both industry and academia. Recently, two commercially available pieces of software have become available. PPHARM was released during 1994 and POPKAN was released in 1995. We provide descriptions and critique the FOCE method within NONMEM, the two-step algorithm within PPHARM and the Markov chain Monte Carlo method that is utilized by POPKAN. We use simulated data generated from a monoexponential model to evaluate the parameter estimation capabilities of these methods within the three software tools. In particular we investigate the effect on parameter estimation of increasing both interindividual and intraindividual variability.

Bayes Theorem↗
PubMed1995

Image quality, the ideal observer, and human performance of radiologic decision tasks.

The quality of medical images must be quantified with reference to specific diagnostic tasks. Image quality is limited by fundamental physics, engineering limitations, radiation safety concerns, and imaging time constraints (among other things). There is now a gold standard for assessing human visual decision performance: the ideal Bayesian observer. Unfortunately, there are no mathematical tools to use this gold standard for realistically complex tasks. As an alternative, one can use the optimum linear discriminator (Fisher-Hotelling) model as a silver standard while en route to clinical realism. The goal of scientists working in the area is to develop mathematical models of human observers that will help equipment designers to optimize design trade-offs for specific diagnostic tasks. The current strategy is to modify the Fisher-Hotelling model to include certain limitations of the human observer visual system. The model must be both robust enough and mathematically tractable enough to be used to predict performance for clinical classification and estimation tasks. Statistical models also must be developed that describe realistic signals (lesions and abnormalities) and the normal patient structure that is the background in which these signals must be detected or identified.

Decision Making↗
PubMed2005

Empirical Bayesian estimation of the disease transmission probability in multiple-vector-transfer designs.

Plant disease is responsible for major losses in agriculture throughout the world. Diseases are often spread by insect organisms that transmit a bacterium, virus, or other pathogen. To assess disease epidemics, plant pathologists often use multiple-vector-transfers. In such contexts, groups of insect vectors are moved from an infected source to each of n test plants that will then be observed for developing symptoms of infection. The purpose of this paper is to present new estimators for p, the probability of pathogen transmission for an individual vector, motivated from an empirical Bayesian approach. We specifically investigate four such estimators, characterize their small-sample properties, and propose new credible intervals for p. These estimators remove the need to specify hyperparameters a priori and are shown to be easier to compute than the classical Bayes estimators proposed by Chaubey and Li (1995, Journal of Official Statistics 11, 1035-1046) and Chick (1996, Biometrics 52, 1055-1062). Furthermore, some of these estimators are shown to have better frequentist properties than the commonly used maximum likelihood estimator and to provide a smaller Bayes risk than the estimator proposed by Burrows (1987, Phytopathology 77, 363-365).

Algorithms↗
PubMed2005

Quantitative magnetic resonance spectroscopy: semi-parametric modeling and determination of uncertainties.

A semi-parametric approach for the quantitative analysis of magnetic resonance (MR) spectra is proposed and an uncertainty analysis is given. Single resonances are described by parametric models or by parametrized in vitro spectra and the baseline is determined nonparametrically by regularization. By viewing baseline estimation in a reproducing kernel Hilbert space, an explicit parametric solution for the baseline is derived. A Bayesian point of view is adopted to derive uncertainties, and the many parameters associated with the baseline solution are treated as nuisance parameters. The derived uncertainties formally reduce to Cramér-Rao lower bounds for the parametric part of the model in the case of a vanishing baseline. The proposed uncertainty calculation was applied to simulated and measured MR spectra and the results were compared to Cramér-Rao lower bounds derived after the nonparametrically estimated baselines were subtracted from the spectra. In particular, for high SNR and strong baseline contributions the proposed procedure yields a more appropriate characterization of the accuracy of parameter estimates than Crémer-Rao lower bounds, which tend to overestimate accuracy.

Bayes Theorem↗
PubMed2004

A comparative evaluation of wavelet-based methods for hypothesis testing of brain activation maps.

Wavelet-based methods for hypothesis testing are described and their potential for activation mapping of human functional magnetic resonance imaging (fMRI) data is investigated. In this approach, we emphasise convergence between methods of wavelet thresholding or shrinkage and the problem of hypothesis testing in both classical and Bayesian contexts. Specifically, our interest will be focused on the trade-off between type I probability error control and power dissipation, estimated by the area under the ROC curve. We describe a technique for controlling the false discovery rate at an arbitrary level of error in testing multiple wavelet coefficients generated by a 2D discrete wavelet transform (DWT) of spatial maps of fMRI time series statistics. We also describe and apply change-point detection with recursive hypothesis testing methods that can be used to define a threshold unique to each level and orientation of the 2D-DWT, and Bayesian methods, incorporating a formal model for the anticipated sparseness of wavelet coefficients representing the signal or true image. The sensitivity and type I error control of these algorithms are comparatively evaluated by analysis of "null" images (acquired with the subject at rest) and an experimental data set acquired from five normal volunteers during an event-related finger movement task. We show that all three wavelet-based algorithms have good type I error control (the FDR method being most conservative) and generate plausible brain activation maps (the Bayesian method being most powerful). We also generalise the formal connection between wavelet-based methods for simultaneous multiresolution denoising/hypothesis testing and methods based on monoresolution Gaussian smoothing followed by statistical testing of brain activation maps.

Algorithms↗
PubMed2006

Inferring global levels of alternative splicing isoforms using a generative model of microarray data.

MOTIVATION: Alternative splicing (AS) is a frequent step in metozoan gene expression whereby the exons of genes are spliced in different combinations to generate multiple isoforms of mature mRNA. AS functions to enrich an organism's proteomic complexity and regulates gene expression. Despite its importance, the mechanisms underlying AS and its regulation are not well understood, especially in the context of global gene expression patterns. We present here an algorithm referred to as the Generative model for the Alternative Splicing Array Platform (GenASAP) that can predict the levels of AS for thousands of exon skipping events using data generated from custom microarrays. GenASAP uses Bayesian learning in an unsupervised probability model to accurately predict AS levels from the microarray data. GenASAP is capable of learning the hybridization profiles of microarray data, while modeling noise processes and missing or aberrant data. GenASAP has been successfully applied to the global discovery and analysis of AS in mammalian cells and tissues. RESULTS: GenASAP was applied to data obtained from a custom microarray designed for the monitoring of 3126 AS events in mouse cells and tissues. The microarray design included probes specific for exon body and junction sequences formed by the splicing of exons. Our results show that GenASAP provides accurate predictions for over one-third of the total events, as verified by independent RT-PCR assays. SUPPLEMENTARY INFORMATION: http://www.psi.toronto.edu/GenASAP.

Algorithms↗
PubMed2003

Bayesian model choice and search strategies for mapping interacting quantitative trait Loci.

Most complex traits of animals, plants, and humans are influenced by multiple genetic and environmental factors. Interactions among multiple genes play fundamental roles in the genetic control and evolution of complex traits. Statistical modeling of interaction effects in quantitative trait loci (QTL) analysis must accommodate a very large number of potential genetic effects, which presents a major challenge to determining the genetic model with respect to the number of QTL, their positions, and their genetic effects. In this study, we use the methodology of Bayesian model and variable selection to develop strategies for identifying multiple QTL with complex epistatic patterns in experimental designs with two segregating genotypes. Specifically, we develop a reversible jump Markov chain Monte Carlo algorithm to determine the number of QTL and to select main and epistatic effects. With the proposed method, we can jointly infer the genetic model of a complex trait and the associated genetic parameters, including the number, positions, and main and epistatic effects of the identified QTL. Our method can map a large number of QTL with any combination of main and epistatic effects. Utility and flexibility of the method are demonstrated using both simulated data and a real data set. Sensitivity of posterior inference to prior specifications of the number and genetic effects of QTL is investigated.

Bayes Theorem↗
PubMed2006

Stochastic methods for joint registration, restoration, and interpolation of multiple undersampled images.

Using a stochastic framework, we propose two algorithms for the problem of obtaining a single high-resolution image from multiple noisy, blurred, and undersampled images. The first is based on a Bayesian formulation that is implemented via the expectation maximization algorithm. The second is based on a maximum a posteriori formulation. In both of our formulations, the registration, noise, and image statistics are treated as unknown parameters. These unknown parameters and the high-resolution image are estimated jointly based on the available observations. We present an efficient implementation of these algorithms in the frequency domain that allows their application to large images. Simulations are presented that test and compare the proposed algorithms.

Algorithms↗
PubMed2001

The effect of branch length variation on the selection of models of molecular evolution.

Models of sequence evolution play an important role in molecular evolutionary studies. The use of inappropriate models of evolution may bias the results of the analysis and lead to erroneous conclusions. Several procedures for selecting the best-fit model of evolution for the data at hand have been proposed, like the likelihood ratio test (LRT) and the Akaike (AIC) and Bayesian (BIC) information criteria. The relative performance of these model-selecting algorithms has not yet been studied under a range of different model trees. In this study, the influence of branch length variation upon model selection is characterized. This is done by simulating sequence alignments under a known model of nucleotide substitution, and recording how often this true model is recovered by different model-fitting strategies. Results of this study agree with previous simulations and suggest that model selection is reasonably accurate. However, different model selection methods showed distinct levels of accuracy. Some LRT approaches showed better performance than the AIC or BIC information criteria. Within the LRTs, model selection is affected by the complexity of the initial model selected for the comparisons, and only slightly by the order in which different parameters are added to the model. A specific hierarchy of LRTs, which starts from a simple model of evolution, performed overall better than other possible LRT hierarchies, or than the AIC or BIC.

Bayes Theorem↗
PubMed2004

Effects of domain-specific knowledge on memory for serial order.

Knowledge concerning domain-specific regularities in sequential structure has long been known to affect recall for serial order. However, very little work has been done toward specifying the exact role such knowledge plays. The present article proposes a theory of serial recall in structured domains, based on Bayesian decision theory and a set of representational assumptions proceeding from recent computational and neurophysiologic research. The theory suggests that the accuracy with which a target sequence will be recalled is influenced by two interacting factors: (1) the 'goodness' of the sequence, i.e. its fit with the sequencing constraints that characterize its source domain, and (2) the sequence's neighborhood relations, i.e. the degree to which it resembles other sequences in the source domain. A specific prediction of the theory is that recall will be relatively poor for target lists with high-goodness near neighbors (the good neighbor effect). This prediction was tested and confirmed in an experiment evaluating recall for sequences based on an artificial grammar.

Adolescent↗
PubMed2006

A hybrid region-boundary model for cerebral cortical segmentation in MRI.

Automatic segmentation of cerebral cortex in magnetic resonance imaging (MRI) is a challenging problem in understanding brain anatomy and functions. The difficulty is mainly due to variable brain structures, various MRI artifacts and restrictive body scanning methods. This paper describes a hybrid model-based method for obtaining an accurate and topologically-preserving segmentation of the brain cortex. The approach is based on defining region and boundary information using, respectively, level set and Bayesian techniques, and fusing these two types of information to achieve cerebral cortex segmentation. It is automatic and robust to noise, intensity inhomogeneities, and partial volume effect. Another particularity of the proposed approach is that bias field is corrected during segmentation process and that the central layer of the cortex is accurately obtained through a topology correction step. The proposed method is evaluated on both simulated and real data, and compared with existing segmentation techniques. The obtained results have demonstrated its improved performance and robustness.

Algorithms↗
PubMed2006

Bayesian analysis of population structure based on linked molecular information.

The Bayesian model-based approach to inferring hidden genetic population structures using multilocus molecular markers has become a popular tool within certain branches of biology. In particular, it has been shown that heterogeneous data arising from genetically dissimilar latent groups of individuals can be effectively modelled using an unsupervised classification formulation. However, most currently employed models ignore potential linkage within the employed molecular information, and can therefore lead to biased inferences under certain circumstances. Utilizing the general theory of graphical models, we develop a framework that accounts for dependences both within linked molecular marker loci and DNA sequence data. Due to a high level of sequence conservation among eukaryotic species, the latter aspect is particularly relevant for analyzing rapidly evolving microbial species. The advantages of incorporating the dependence due to linkage in the classification models are illustrated by analyses of both simulated data and real samples of Bacillus cereus.

Bacillus cereus↗
PubMed2004

Bayesian model averaging in EEG/MEG imaging.

In this paper, the Bayesian Theory is used to formulate the Inverse Problem (IP) of the EEG/MEG. This formulation offers a comparison framework for the wide range of inverse methods available and allows us to address the problem of model uncertainty that arises when dealing with different solutions for a single data. In this case, each model is defined by the set of assumptions of the inverse method used, as well as by the functional dependence between the data and the Primary Current Density (PCD) inside the brain. The key point is that the Bayesian Theory not only provides for posterior estimates of the parameters of interest (the PCD) for a given model, but also gives the possibility of finding posterior expected utilities unconditional on the models assumed. In the present work, this is achieved by considering a third level of inference that has been systematically omitted by previous Bayesian formulations of the IP. This level is known as Bayesian model averaging (BMA). The new approach is illustrated in the case of considering different anatomical constraints for solving the IP of the EEG in the frequency domain. This methodology allows us to address two of the main problems that affect linear inverse solutions (LIS): (a) the existence of ghost sources and (b) the tendency to underestimate deep activity. Both simulated and real experimental data are used to demonstrate the capabilities of the BMA approach, and some of the results are compared with the solutions obtained using the popular low-resolution electromagnetic tomography (LORETA) and its anatomically constraint version (cLORETA).

Artifacts↗
PubMed2003

A multi-agent intelligent environment for medical knowledge.

AMPLIA is a multi-agent intelligent learning environment designed to support training of diagnostic reasoning and modelling of domains with complex and uncertain knowledge. AMPLIA focuses on the medical area. It is a system that deals with uncertainty under the Bayesian network approach, where learner-modelling tasks will consist of creating a Bayesian network for a problem the system will present. The construction of a network involves qualitative and quantitative aspects. The qualitative part concerns the network topology, that is, causal relations among the domain variables. After it is ready, the quantitative part is specified. It is composed of the distribution of conditional probability of the variables represented. A negotiation process (managed by an intelligent MediatorAgent) will treat the differences of topology and probability distribution between the model the learner built and the one built-in in the system. That negotiation process occurs between the agents that represent the expert knowledge domain (DomainAgent) and the agent that represents the learner knowledge (LearnerAgent).

Artificial Intelligence↗
PubMed2005

Estimating time-dependent gene networks from time series microarray data by dynamic linear models with Markov switching.

In gene network estimation from time series microarray data, dynamic models such as differential equations and dynamic Bayesian networks assume that the network structure is stable through all time points, while the real network might changes its structure depending on time, affection of some shocks and so on. If the true network structure underlying the data changes at certain points, the fitting of the usual dynamic linear models fails to estimate the structure of gene network and we cannot obtain efficient information from data. To solve this problem, we propose a dynamic linear model with Markov switching for estimating time-dependent gene network structure from time series gene expression data. Using our proposed method, the network structure between genes and its change points are automatically estimated. We demonstrate the effectiveness of the proposed method through the analysis of Saccharomyces cerevisiae cell cycle time series data.

Algorithms↗
PubMed1994

Mixed Bayesian networks: a mixture of Gaussian distributions.

Mixed Bayesian networks are probabilistic models associated with a graphical representation, where the graph is directed and the random variables are discrete or continuous. We propose a comprehensive method for estimating the density functions of continuous variables, using a graph structure and a set of samples. The principle of the method is to learn the shape of densities from a sample of continuous variables. The densities are approximated by a mixture of Gaussian distributions. The estimation algorithm is a stochastic version of the Expectation Maximization algorithm (Stochastic EM algorithm). The inference algorithm corresponding to our model is a variant of junction three method, adapted to our specific case. The approach is illustrated by a simulated example from the domain of pharmacokinetics. Tests show that the true distributions seem sufficiently fitted for practical application.

Algorithms↗