Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bayesian computational modeling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77Linked to original sources

Automatic basis selection techniques for RBF networks.

This paper proposes a generic criterion that defines the optimum number of basis functions for radial basis function (RBF) neural networks. The generalization performance of an RBF network relates to its prediction capability on independent test data. This performance gives a measure of the quality of the chosen model. An RBF network with an overly restricted basis gives poor predictions on new data, since the model has too little flexibility (yielding high bias and low variance). By contrast, an RBF network with too many basis functions also gives poor generalization performance since it is too flexible and fits too much of the noise on the training data (yielding low bias but high variance). Bias and variance are complementary quantities, and it is necessary to assign the number of basis function optimally in order to achieve the best compromise between them. In this paper we use Stein's unbiased risk estimator to derive an analytical criterion for assigning the appropriate number of basis functions. Two cases of known and unknown noise have been considered and the efficacy of this criterion in both situations is illustrated experimentally. The paper also shows an empirical comparison between this method and two well known classical methods, cross validation and the Bayesian information criterion, BIC.

Electronic Data Processing↗

Variational learning for Gaussian mixture models.

This paper proposes a joint maximum likelihood and Bayesian methodology for estimating Gaussian mixture models. In Bayesian inference, the distributions of parameters are modeled, characterized by hyperparameters. In the case of Gaussian mixtures, the distributions of parameters are considered as Gaussian for the mean, Wishart for the covariance, and Dirichlet for the mixing probability. The learning task consists of estimating the hyperparameters characterizing these distributions. The integration in the parameter space is decoupled using an unsupervised variational methodology entitled variational expectation-maximization (VEM). This paper introduces a hyperparameter initialization procedure for the training algorithm. In the first stage, distributions of parameters resulting from successive runs of the expectation-maximization algorithm are formed. Afterward, maximum-likelihood estimators are applied to find appropriate initial values for the hyperparameters. The proposed initialization provides faster convergence, more accurate hyperparameter estimates, and better generalization for the VEM training algorithm. The proposed methodology is applied in blind signal detection and in color image segmentation.

Algorithms↗

Connectionist-based Dempster-Shafer evidential reasoning for data fusion.

Dempster-Shafer evidence theory (DSET) is a popular paradigm for dealing with uncertainty and imprecision. Its corresponding evidential reasoning framework is theoretically attractive. However, there are outstanding issues that hinder its use in real-life applications. Two prominent issues in this regard are 1) the issue of basic probability assignments (masses) and 2) the issue of dependence among information sources. This paper attempts to deal with these issues by utilizing neural networks in the context of pattern classification application. First, a multilayer perceptron neural network with the mean squared error as a cost function is implemented to calculate, for each information source, posteriori probabilities for all classes. Second, an evidence structure construction scheme is developed for transferring the estimated posteriori probabilities to a set of masses along with the corresponding focal elements, from a Bayesian decision point of view. Third, a network realization of the Dempster-Shafer evidential reasoning is designed and analyzed, and it is further extended to a DSET-based neural network, referred to as DSETNN, to manipulate the evidence structures. In order to tackle the issue of dependence between sources, DSETNN is tuned for optimal performance through a supervised learning process. To demonstrate the effectiveness of the proposed approach, we apply it to three benchmark pattern classification problems. Experiments reveal that the DSETNN out-performs DSET and provide encouraging results in terms of classification accuracy and the speed of learning convergence.

Algorithms↗

Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application.

To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3'-hydroxycotinine (3HC) measurements. COT and 3HC saliva concentrations in smokers were simulated utilizing a mechanistic population pharmacokinetic model of NIC metabolism that was adapted from the one described in a companion paper. Four methods to predict NIC clearance using the metabolites concentrations were compared. The precision bias, and the fraction of predictions that are made with an absolute error below 25% were the performance measures evaluated. Four prediction methods were compared: (M1) reference method, an intercept slope model of the metabolite concentration ratios ([3HC]/[COT]) (M2) an intercept slope model of the natural logarithm of the metabolite ratios (M3) a spline of the logarithm of the metabolite ratios (M4) Maximal Posteriori Bayesian estimate of NIC clearance conditioned on the model, COT and 3HC concentrations. In addition, the effect of smoking patterns on the concentrations of COT and 3HC was evaluated. The precision, accuracy, and the fraction of predictions with an absolute error below 25%, were higher for methods M2-M4 compared to method M1. However, the differences between M2 and M4 were small. Additionally, smoking pattern did not affect the metabolite concentration profiles. Predicting NIC clearance using an intercept slope model of the natural logarithm of the ratio of 3HC to COT appears to be a relatively simple method that is better than using the metabolite ratio directly. This method has a bias of approximately -10%, precision of approximately 60%. The fraction of estimates below an absolute error of 25% is 43%. These results support use of M2 to estimate CYP2A6 activity in smokers in the clinical setting.

Aryl Hydrocarbon Hydroxylases↗

Core passive and facultative mTOR-mediated mechanisms coordinate mammalian protein synthesis and decay.

The maintenance of cellular homeostasis requires tight regulation of proteome concentration and composition. To achieve this, protein production and elimination must be robustly coordinated. However, the mechanistic basis of this coordination remains unclear. Here, we address this question using quantitative live-cell imaging, computational modeling, transcriptomics, and proteomics approaches. We found that protein decay rates systematically adapt to global alterations of protein synthesis rates. This adaptation is driven by a core passive mechanism supplemented by facultative changes in mechanistic/mammalian target of rapamycin (mTOR) signaling. Passive adaptation hinges on changes in the production rate of the machinery governing protein decay and allows for partial maintenance of the cellular proteome. Sustained changes in mTOR signaling provide an additional layer of adaptation unique to naive pluripotent stem cells, allowing for near-perfect maintenance of proteome composition. Our work unravels the mechanisms protecting the integrity of mammalian proteomes upon variations in protein synthesis rates. A record of this paper's transparent peer review process is included in the supplemental information.

TOR Serine-Threonine Kinases↗

Multivariate information bottleneck.

The information bottleneck (IB) method is an unsupervised model independent data organization technique. Given a joint distribution, p(X, Y), this method constructs a new variable, T, that extracts partitions, or clusters, over the values of X that are informative about Y. Algorithms that are motivated by the IB method have already been applied to text classification, gene expression, neural code, and spectral analysis. Here, we introduce a general principled framework for multivariate extensions of the IB method. This allows us to consider multiple systems of data partitions that are interrelated. Our approach utilizes Bayesian networks for specifying the systems of clusters and which information terms should be maintained. We show that this construction provides insights about bottleneck variations and enables us to characterize the solutions of these variations. We also present four different algorithmic approaches that allow us to construct solutions in practice and apply them to several real-world problems.

Algorithms↗

Estimation of linkage disequilibrium in a sample of the United Kingdom dairy cattle population using unphased genotypes.

The association between genetic marker alleles was estimated for two regions of the bovine genome from a random sample of 50 young dairy bulls born in the United Kingdom between 1988 and 1995. Microsatellite marker genotypes were obtained for six markers on chromosome 2 and seven markers on chromosome 6, spanning 38 and 20 cM, respectively. Two different methods, which do not require family information, were used to estimate population haplotype frequencies. Haplotype frequencies were estimated for pairs of loci using the expectation-maximization algorithm and for all linked loci using a Bayesian approach via a Markov chain-Monte Carlo algorithm. Significant (P = 0.0007) linkage disequilibrium was detected between pairs of loci in syntenic groups (that is, loci in the same linkage group), extending to about 10 cM. No significant linkage disequilibrium was detected between markers in nonsyntenic regions. Given the observed level of linkage disequilibrium, mapping methods based on population-wide association might provide a better resolution than traditional quantitative trait loci mapping methods in the U.K. dairy cattle population and may reduce the required sample sizes of the experiments.

Algorithms↗

Non-linear registration for brain images by maximising feature and intensity similarities with a Bayesian framework.

The objective of this work was to provide a new, precise registration of the cortical mantle with a non-linear transformation. Image registration is broadly classified into two types, using intensity similarity and feature similarity. Whereas the former approach has merit in global brain matching, the latter provides a fast registration centred on a region of interest. The hybrid registration proposed in this paper was achieved using a Bayesian framework, which consisted of a likelihood model including intensity similarity and a prior model including feature information and a smoothing constraint. In this approach, each voxel was spatially transformed, so that the distance between corresponding features was shortened and also so that the intensity correlation was maximised. The result of the hybrid method clearly showed a good match of global brain (r = 0.930) by including intensity similarity. Moreover, this method compensated for the approximated sulcus of the feature-based method with intensity information, so that the geometric shape and thickness of the sulcus at the feature-defined region was likely to be registered. The accuracy in the feature-defined area was improved by 33.4% and 7.5% compared with feature-based and intensity-based methods, respectively.

Bayes Theorem↗

Penalized likelihood approach to estimate a smooth mean curve on longitudinal data.

This paper aims to propose a penalized likelihood approach to estimate a smooth mean curve for the evolution with time of a Gaussian variable taking into account the correlation structure of longitudinal data. The model is an extension of the mixed effects linear model including an unspecified function of time f(t). The estimator (circumflex)f(t) is defined as the solution of the maximization of the penalized likelihood and is approximated on a basis of cubic M-spline with a reduced number of knots. We present modifications of four criteria (cross-validation, generalized cross-validation, T of Rice, Akaike's criterion) to estimate the smoothing parameter when data are correlated; these four criteria gave very similar results in the simulation study. The simulation study showed also the superiority of the Bayesian confidence bands of the mean curve over the frequentist ones. We develop empirical Bayes estimates of subject-specific deviations. This approach was applied to study the progression of CD4+ lymphocyte counts in a cohort of HIV patients treated with protease inhibitors.

Acquired Immunodeficiency Syndrome↗

Exploration of event-induced EEG phase synchronization patterns in cognitive tasks using a time-frequency-topography visualization system.

In this paper, we present a method for the study of synchronization patterns measured from EEG scalp potentials in psychophysiological experiments. This method is based on various techniques: a time-frequency decomposition using sinusoidal filters which improve phase accuracy for low frequencies, a Bayesian approach for the estimation of significant synchrony changes, and a time-frequency-topography visualization technique which allows for easy exploration and provides detailed insights of a particular experiment. Particularly, we focus on in-phase synchrony using an instantaneous phase-lock measure. We also discuss some of the most common methods in the literature, focusing on their relevance to long-range synchrony analysis; this discussion includes a comparison among various synchrony measures. Finally, we present the analysis of a figure categorization experiment to illustrate our method.

Bayes Theorem↗

Improved fiber tractography with Bayesian tensor regularization.

Diffusion tensor tractography suffers from the effects of noise and partial volume averaging (PVA). For reliable reconstruction of fiber pathways, tracking algorithms that are robust to these artifacts are called for. To meet this need, the present study establishes a novel Bayesian regularization framework for fiber tracking that takes into account the effects of noise and PVA, thereby improving tracking accuracy and precision. With this framework, the propagation of a fiber path follows an optimal vector determined by Bayes decision rule; the probability functions involved are modeled on the basis of multivariate normal distributions of diffusion tensor elements, which allows the optimal solution with maximum a posteriori probability to be derived analytically. Parameters for the probability functions are estimated from the uncertainty of tensor elements and the variance among tensors within an oriented sampling volume weighted by fractional anisotropy. Experiments with Monte Carlo simulations, synthetic, and in vivo human diffusion tensor data demonstrate that this specialized scheme enhances the immunity of fiber tracking to noise and PVA, and hence enables fibers to be more faithfully reconstructed.

Adult↗

On visualization and aggregation of nearest neighbor classifiers.

Nearest neighbor classification is one of the simplest and most popular methods for statistical pattern recognition. A major issue in k-nearest neighbor classification is how to find an optimal value of the neighborhood parameter k. In practice, this value is generally estimated by the method of cross-validation. However, the ideal value of k in a classification problem not only depends on the entire data set, but also on the specific observation to be classified. Instead of using any single value of k, this paper studies results for a finite sequence of classifiers indexed by k. Along with the usual posterior probability estimates, a new measure, called the Bayesian measure of strength, is proposed and investigated in this paper as a measure of evidence for different classes. The results of these classifiers and their corresponding estimated misclassification probabilities are visually displayed using shaded strips. These plots provide an effective visualization of the evidence in favor of different classes when a given data point is to be classified. We also propose a simple weighted averaging technique that aggregates the results of different nearest neighbor classifiers to arrive at the final decision. Based on the analysis of several benchmark data sets, the proposed method is found to be better than using a single value of k.

Algorithms↗

New methods for detecting positive selection at single amino acid sites.

Inferring positive selection at single amino acid sites is of particular importance for studying evolutionary mechanisms of a protein. For this purpose, Suzuki and Gojobori (1999) developed a method (SG method) for comparing the rates of synonymous and nonsynonymous substitutions at each codon site in a protein-coding nucleotide sequence, using ancestral codons at interior nodes of the phylogenetic tree as inferred by the maximum parsimony method. In the SG method, however, selective neutrality of nucleotide substitutions cannot be tested at codon sites, where only termination codons are inferred at any interior node or the number of equally parsimonious inferences of ancestral codons at all interior nodes exceeds 10,000. Here I present a modified SG method which is free from these problems. Specifically, I use the distance-based Bayesian method for inferring the single most likely ancestral codon from 61 sense codons at each interior node. In the computer simulation and real data analysis, the modified SG method showed a higher overall efficiency of detecting positive selection than the original SG method, particularly at highly polymorphic codon sites. These results indicate that the modified SG method is useful for inferring positive selection at codon sites where neutrality cannot be tested by the original SG method. I also discuss that the p-distance is preferable to the number of synonymous substitutions for inferring the phylogenetic tree in the SG method, and present a maximum likelihood method for detecting positive selection at single amino acid sites, which produced reasonable results in the real data analysis.

Amino Acids↗

Toxicity-indicating structural patterns.

We describe a toxicity alerting system for uncharacterized compounds, which is based upon comprehensive tables of substructure fragments that are indicative of toxicity risk. These tables were derived computationally by analyzing the RTECS database and the World Drug Index. We provide, free of charge, a Java applet for structure drawing and toxicity risk assessment. In an independent investigation, we compared the toxicity classification performance of naive Bayesian clustering, k next neighbor classification, and support vector machines. To visualize the chemical space of both toxic and druglike molecules, we trained a large self-organizing map (SOM) with all compounds from the RTECS database and the IDDB. In summary, we found that a support vector machine performed best at classifying compounds of defined toxicity into appropriate toxicity classes. Also, SOMs performed excellently in separating toxic from nontoxic substances. Although these two methods are limited to compounds that are structurally similar to known toxic substances, our fragment-based approach extends predictions to compounds that are structurally dissimilar to compounds used in the training set.

Bayes Theorem↗

Bayesian approaches for the analysis of population genetic structure: an example from Platanthera leucophaea (Orchidaceae).

We describe four extensions to existing Bayesian methods for the analysis of genetic structure in populations: (i) use of beta distributions to approximate the posterior distribution of f and theta(B); (ii) use of an entropy statistic to describe the amount of information about a parameter derived from the data; (iii) use of the Deviance Information Criterion (DIC) as a model choice criterion for determining whether there is evidence for inbreeding within populations or genetic differentiation among populations; and (iv) use of samples from the posterior distributions for f and theta(B) derived from different data sets to determine whether the estimates are consistent with one another. We illustrate each of these extensions by applying them to data derived from previous allozyme and random amplified polymorphic DNA surveys of an endangered orchid, Platanthera leucophaea, and we conclude that differences in theta(B) from the two data sets may represent differences in the underlying mutational processes.

Bayes Theorem↗

Modeling of cyclin-dependent kinase inhibition by 1H-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles.

Artificial neural network ensembles were used for modeling the cyclin-dependent kinase inhibition of 1H-pyrazolo[3,4-d]pyrimidine derivatives. The structural characteristics of these inhibitors were encoded in relevant 3D-spatial descriptors extracted by genetic algorithm feature selection. Bayesian-regularized multilayer neural networks, trained by the back-propagation algorithm, were developed using these variables as inputs. The predictive power of the model was tested by leave-one-out cross validation. In addition, for a more rigorous measure of the predictive capacity, multiple validation sets were randomly generated as members of neural network ensembles, which makes doing averaged predictions feasible. In this way, the predictive power was analyzed accounting for the averaged test set R values and test set mean-square errors. Otherwise, Kohonen self-organizing maps were used as an additional tool for the same modeling. The location of the inhibitors in a map facilitates the analysis of the connection between compounds and serves as a useful tool for qualitative predictions.

Algorithms↗

An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network.

P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding cytotoxic agents out of cells, resulting in an obstacle in chemotherapeutic treatment of cancer. In order to aid in the development of potential P-gp inhibitors, we constructed a quantitative structure-activity relationship (QSAR) model of flavonoids as P-gp inhibitors based on Bayesian-regularized neural network (BRNN). A dataset of 57 flavonoids collected from a literature binding to the C-terminal nucleotide-binding domain of mouse P-gp was compiled. The predictive ability of the model was assessed using a test set that was independent of the training set, which showed a standard error of prediction of 0.146+/-0.006 (data scaled from 0 to 1). Meanwhile, two other mathematical tools, back-propagation neural network (BPNN) and partial least squares (PLS) were also attempted to build QSAR models. The BRNN provided slightly better results for the test set compared to BPNN, but the difference was not significant according to F-statistic at p=0.05. The PLS failed to build a reliable model in the present study. Our study indicates that the BRNN-based in silico model has good potential in facilitating the prediction of P-gp flavonoid inhibitors and might be applied in further drug design.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cancer classification and prediction using logistic regression with Bayesian gene selection.

In microarray-based cancer classification and prediction, gene selection is an important research problem owing to the large number of genes and the small number of experimental conditions. In this paper, we propose a Bayesian approach to gene selection and classification using the logistic regression model. The basic idea of our approach is in conjunction with a logistic regression model to relate the gene expression with the class labels. We use Gibbs sampling and Markov chain Monte Carlo (MCMC) methods to discover important genes. To implement Gibbs Sampler and MCMC search, we derive a posterior distribution of selected genes given the observed data. After the important genes are identified, the same logistic regression model is then used for cancer classification and prediction. Issues for efficient implementation for the proposed method are discussed. The proposed method is evaluated against several large microarray data sets, including hereditary breast cancer, small round blue-cell tumors, and acute leukemia. The results show that the method can effectively identify important genes consistent with the known biological findings while the accuracy of the classification is also high. Finally, the robustness and sensitivity properties of the proposed method are also investigated.

Algorithms↗