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Analyzing symmetry breaking within a chaotic quantum system via bayesian inference

Bayesian inference is applied to the level fluctuations of two coupled microwave billiards in order to extract the coupling strength. The coupled resonators provide a model of a chaotic quantum system containing two coupled symmetry classes of levels. The number variance is used to quantify the level fluctuations as a function of the coupling and to construct the conditional probability distribution of the data. The prior distribution of the coupling parameter is obtained from an invariance argument on the entropy of the posterior distribution.

Journal Article↗

Spatiotemporal Bayesian inference dipole analysis for MEG neuroimaging data.

Recently, we described a Bayesian inference approach to the MEG/EEG inverse problem that used numerical techniques to estimate the full posterior probability distributions of likely solutions upon which all inferences were based [Schmidt, D.M., George, J.S., Wood, C.C., 1999. Bayesian inference applied to the electromagnetic inverse problem. Human Brain Mapping 7, 195; Schmidt, D.M., George, J.S., Ranken, D.M., Wood, C.C., 2001. Spatial-temporal bayesian inference for MEG/EEG. In: Nenonen, J., Ilmoniemi, R. J., Katila, T. (Eds.), Biomag 2000: 12th International Conference on Biomagnetism. Espoo, Norway, p. 671]. Schmidt et al. (1999) focused on the analysis of data at a single point in time employing an extended region source model. They subsequently extended their work to a spatiotemporal Bayesian inference analysis of the full spatiotemporal MEG/EEG data set. Here, we formulate spatiotemporal Bayesian inference analysis using a multi-dipole model of neural activity. This approach is faster than the extended region model, does not require use of the subject's anatomical information, does not require prior determination of the number of dipoles, and yields quantitative probabilistic inferences. In addition, we have incorporated the ability to handle much more complex and realistic estimates of the background noise, which may be represented as a sum of Kronecker products of temporal and spatial noise covariance components. This reduces the effects of undermodeling noise. In order to reduce the rigidity of the multi-dipole formulation which commonly causes problems due to multiple local minima, we treat the given covariance of the background as uncertain and marginalize over it in the analysis. Markov Chain Monte Carlo (MCMC) was used to sample the many possible likely solutions. The spatiotemporal Bayesian dipole analysis is demonstrated using simulated and empirical whole-head MEG data.

Algorithms↗

Identifiability of parameters in MCMC Bayesian inference of phylogeny.

Methods for Bayesian inference of phylogeny using DNA sequences based on Markov chain Monte Carlo (MCMC) techniques allow the incorporation of arbitrarily complex models of the DNA substitution process, and other aspects of evolution. This has increased the realism of models, potentially improving the accuracy of the methods, and is largely responsible for their recent popularity. Another consequence of the increased complexity of models in Bayesian phylogenetics is that these models have, in several cases, become overparameterized. In such cases, some parameters of the model are not identifiable; different combinations of nonidentifiable parameters lead to the same likelihood, making it impossible to decide among the potential parameter values based on the data. Overparameterized models can also slow the rate of convergence of MCMC algorithms due to large negative correlations among parameters in the posterior probability distribution. Functions of parameters can sometimes be found, in overparameterized models, that are identifiable, and inferences based on these functions are legitimate. Examples are presented of overparameterized models that have been proposed in the context of several Bayesian methods for inferring the relative ages of nodes in a phylogeny when the substitution rate evolves over time.

Algorithms↗

Potential applications and pitfalls of Bayesian inference of phylogeny.

Only recently has Bayesian inference of phylogeny been proposed. The method is now a practical alternative to the other methods; indeed, the method appears to possess advantages over the other methods in terms of ability to use complex models of evolution, ease of interpretation of the results, and computational efficiency. However, the method should be used cautiously. The results of a Bayesian analysis should be examined with respect to the sensitivity of the results to the priors used and the reliability of the Markov chain Monte Carlo approximation of the probabilities of trees.

Bayes Theorem↗

Case-control studies and Bayesian inference.

We outline the methods of Bayesian inference for applications to case-control studies. These methods appear as the natural way of making inferences, since much of the controversy that surrounds a specific case-control study is subjective. We derive conjugate prior distributions of exposure, posterior distributions of the ratio of the odds of being incident with a disease both with and without exposure to a potential causal agent, and convenient approximations. In particular, we show how one may carry out 'case-control studies' without necessarily having a control group. We illustrate these ideas with the data that first showed the relationship between in utero exposure to diethylstilbestrol and cancer of the vagina in young girls.

Adenocarcinoma↗

Bayesian inference on biopolymer models.

MOTIVATION: Most existing bioinformatics methods are limited to making point estimates of one variable, e.g. the optimal alignment, with fixed input values for all other variables, e.g. gap penalties and scoring matrices. While the requirement to specify parameters remains one of the more vexing issues in bioinformatics, it is a reflection of a larger issue: the need to broaden the view on statistical inference in bioinformatics. RESULTS: The assignment of probabilities for all possible values of all unknown variables in a problem in the form of a posterior distribution is the goal of Bayesian inference. Here we show how this goal can be achieved for most bioinformatics methods that use dynamic programming. Specifically, a tutorial style description of a Bayesian inference procedure for segmentation of a sequence based on the heterogeneity in its composition is given. In addition, full Bayesian inference algorithms for sequence alignment are described. AVAILABILITY: Software and a set of transparencies for a tutorial describing these ideas are available at http://www.wadsworth.org/res&res/bioinfo/

Bayes Theorem↗

Bayesian inference with probabilistic population codes.

Recent psychophysical experiments indicate that humans perform near-optimal Bayesian inference in a wide variety of tasks, ranging from cue integration to decision making to motor control. This implies that neurons both represent probability distributions and combine those distributions according to a close approximation to Bayes' rule. At first sight, it would seem that the high variability in the responses of cortical neurons would make it difficult to implement such optimal statistical inference in cortical circuits. We argue that, in fact, this variability implies that populations of neurons automatically represent probability distributions over the stimulus, a type of code we call probabilistic population codes. Moreover, we demonstrate that the Poisson-like variability observed in cortex reduces a broad class of Bayesian inference to simple linear combinations of populations of neural activity. These results hold for arbitrary probability distributions over the stimulus, for tuning curves of arbitrary shape and for realistic neuronal variability.

Algorithms↗

Bayesian inference for model-based segmentation of computed radiographs of the hand.

We present a method for medical image understanding by computer that uses model-based, hierarchical Bayesian inference to accurately segment imaged anatomy. A first application is a prototype system that automatically segments and measures symptoms of arthridities in hand radiographs. This is potentially useful in radiological diagnosis and tracking of arthridities. Key steps of the model-based, Bayesian inference approach are: (1) prediction of imagery features from 3D models of anatomy, parameterized by population statistics, (2) local image feature extraction in predicted sub-regions, and (3) the use of a probabilistic calculus to accrue results of image processing and image feature matching procedures in support or denial of hypotheses about the imaged anatomy. The prototype system for hand radiograph analysis accurately segments normal and somewhat degenerated hand anatomy. Results are shown of the ability of the automated system to 'fail soft', recognizing when segmentation is inadequate for accurate measurement. This self evaluation capability improves reliability of measurements for potential clinical use.

Arthritis↗

Bayesian inference for psychometric functions.

In psychophysical studies, the psychometric function is used to model the relation between physical stimulus intensity and the observer's ability to detect or discriminate between stimuli of different intensities. In this study, we propose the use of Bayesian inference to extract the information contained in experimental data to estimate the parameters of psychometric functions. Because Bayesian inference cannot be performed analytically, we describe how a Markov chain Monte Carlo method can be used to generate samples from the posterior distribution over parameters. These samples are used to estimate Bayesian confidence intervals and other characteristics of the posterior distribution. In addition, we discuss the parameterization of psychometric functions and the role of prior distributions in the analysis. The proposed approach is exemplified using artificially generated data and in a case study for real experimental data. Furthermore, we compare our approach with traditional methods based on maximum likelihood parameter estimation combined with bootstrap techniques for confidence interval estimation and find the Bayesian approach to be superior.

Bayes Theorem↗

MRBAYES: Bayesian inference of phylogenetic trees.

SUMMARY: The program MRBAYES performs Bayesian inference of phylogeny using a variant of Markov chain Monte Carlo. AVAILABILITY: MRBAYES, including the source code, documentation, sample data files, and an executable, is available at http://brahms.biology.rochester.edu/software.html.

Algorithms↗

Classical and Bayesian inference in neuroimaging: theory.

This paper reviews hierarchical observation models, used in functional neuroimaging, in a Bayesian light. It emphasizes the common ground shared by classical and Bayesian methods to show that conventional analyses of neuroimaging data can be usefully extended within an empirical Bayesian framework. In particular we formulate the procedures used in conventional data analysis in terms of hierarchical linear models and establish a connection between classical inference and parametric empirical Bayes (PEB) through covariance component estimation. This estimation is based on an expectation maximization or EM algorithm. The key point is that hierarchical models not only provide for appropriate inference at the highest level but that one can revisit lower levels suitably equipped to make Bayesian inferences. Bayesian inferences eschew many of the difficulties encountered with classical inference and characterize brain responses in a way that is more directly predicated on what one is interested in. The motivation for Bayesian approaches is reviewed and the theoretical background is presented in a way that relates to conventional methods, in particular restricted maximum likelihood (ReML). This paper is a technical and theoretical prelude to subsequent papers that deal with applications of the theory to a range of important issues in neuroimaging. These issues include; (i) Estimating nonsphericity or variance components in fMRI time-series that can arise from serial correlations within subject, or are induced by multisubject (i.e., hierarchical) studies. (ii) Spatiotemporal Bayesian models for imaging data, in which voxels-specific effects are constrained by responses in other voxels. (iii) Bayesian estimation of nonlinear models of hemodynamic responses and (iv) principled ways of mixing structural and functional priors in EEG source reconstruction. Although diverse, all these estimation problems are accommodated by the PEB framework described in this paper.

Algorithms↗

Classical and Bayesian inference in neuroimaging: applications.

In Friston et al. ((2002) Neuroimage 16: 465-483) we introduced empirical Bayes as a potentially useful way to estimate and make inferences about effects in hierarchical models. In this paper we present a series of models that exemplify the diversity of problems that can be addressed within this framework. In hierarchical linear observation models, both classical and empirical Bayesian approaches can be framed in terms of covariance component estimation (e.g., variance partitioning). To illustrate the use of the expectation-maximization (EM) algorithm in covariance component estimation we focus first on two important problems in fMRI: nonsphericity induced by (i) serial or temporal correlations among errors and (ii) variance components caused by the hierarchical nature of multisubject studies. In hierarchical observation models, variance components at higher levels can be used as constraints on the parameter estimates of lower levels. This enables the use of parametric empirical Bayesian (PEB) estimators, as distinct from classical maximum likelihood (ML) estimates. We develop this distinction to address: (i) The difference between response estimates based on ML and the conditional means from a Bayesian approach and the implications for estimates of intersubject variability. (ii) The relationship between fixed- and random-effect analyses. (iii) The specificity and sensitivity of Bayesian inference and, finally, (iv) the relative importance of the number of scans and subjects. The forgoing is concerned with within- and between-subject variability in multisubject hierarchical fMRI studies. In the second half of this paper we turn to Bayesian inference at the first (within-voxel) level, using PET data to show how priors can be derived from the (between-voxel) distribution of activations over the brain. This application uses exactly the same ideas and formalism but, in this instance, the second level is provided by observations over voxels as opposed to subjects. The ensuing posterior probability maps (PPMs) have enhanced anatomical precision and greater face validity, in relation to underlying anatomy. Furthermore, in comparison to conventional SPMs they are not confounded by the multiple comparison problem that, in a classical context, dictates high thresholds and low sensitivity. We conclude with some general comments on Bayesian approaches to image analysis and on some unresolved issues.

Algorithms↗

Ecdysozoan phylogeny and Bayesian inference: first use of nearly complete 28S and 18S rRNA gene sequences to classify the arthropods and their kin.

Relationships among the ecdysozoans, or molting animals, have been difficult to resolve. Here, we use nearly complete 28S+18S ribosomal RNA gene sequences to estimate the relations of 35 ecdysozoan taxa, including newly obtained 28S sequences from 25 of these. The tree-building algorithms were likelihood-based Bayesian inference and minimum-evolution analysis of LogDet-transformed distances, and hypotheses were tested wth parametric bootstrapping. Better taxonomic resolution and recovery of established taxa were obtained here, especially with Bayesian inference, than in previous parsimony-based studies that used 18S rRNA sequences (or 18S plus small parts of 28S). In our gene trees, priapulan worms represent the basal ecdysozoans, followed by nematomorphs, or nematomorphs plus nematodes, followed by Panarthropoda. Panarthropoda was monophyletic with high support, although the relationships among its three phyla (arthropods, onychophorans, tardigrades) remain uncertain. The four groups of arthropods-hexapods (insects and related forms), crustaceans, chelicerates (spiders, scorpions, horseshoe crabs), and myriapods (centipedes, millipedes, and relatives)-formed two well-supported clades: Hexapoda in a paraphyletic crustacea (Pancrustacea), and 'Chelicerata+Myriapoda' (a clade that we name 'Paradoxopoda'). Pycnogonids (sea spiders) were either chelicerates or part of the 'chelicerate+myriapod' clade, but not basal arthropods. Certain clades derived from morphological taxonomy, such as Mandibulata, Atelocerata, Schizoramia, Maxillopoda and Cycloneuralia, are inconsistent with these rRNA data. The 28S gene contained more signal than the 18S gene, and contributed to the improved phylogenetic resolution. Our findings are similar to those obtained from mitochondrial and nuclear (e.g., elongation factor, RNA polymerase, Hox) protein-encoding genes, and should revive interest in using rRNA genes to study arthropod and ecdysozoan relationships.

Animals↗

Bayesian inference in populations of cortical neurons: a model of motion integration and segmentation in area MT.

A major issue in cortical physiology and computational neuroscience is understanding the interaction between extrinsic signals from feedforward connections and intracortical signals from lateral connections. We propose here a computational model for motion perception based on the assumption that the local cortical circuits in the medio-temporal area (area MT) implement a Bayesian inference principle. This approach establishes a functional balance between feedforward and lateral, excitatory and inhibitory, inputs. The model reproduces most of the known properties of the neurons in area MT in response to moving stimuli. It accounts for important motion perception phenomena including motion transparency, spatial and temporal integration/segmentation. While integrating several properties of previously proposed models, it makes specific testable predictions concerning, in particular, temporal properties of neurons and the architecture of lateral connections in area MT. In addition, the proposed mechanism is consistent with the known properties of local cortical circuits in area V1. This suggests that Bayesian inference may be a general feature of information processing in cortical neuron populations.

Animals↗

Bayesian inference for prevalence in longitudinal two-phase studies.

We consider Bayesian inference and model selection for prevalence estimation using a longitudinal two-phase design in which subjects initially receive a low-cost screening test followed by an expensive diagnostic test conducted on several occasions. The change in the subject's diagnostic probability over time is described using four mixed-effects probit models in which the subject-specific effects are captured by latent variables. The computations are performed using Markov chain Monte Carlo methods. These models are then compared using the deviance information criterion. The methodology is illustrated with an analysis of alcohol and drug use in adolescents using data from the Great Smoky Mountains Study.

Adolescent↗

Improving source detection and separation in a spatiotemporal Bayesian inference dipole analysis.

Most existing spatiotemporal multi-dipole approaches for MEG/EEG source localization assume that the dipoles are active for the full time range being analysed. If the actual time range of activity of sources is significantly shorter than the time range being analysed, the detectability, localization and time-course determination of such sources may be adversely affected, especially for weak sources. In order to improve detectability and reconstruction of such sources, it is natural to add active time range information (starting time point and ending time point of source activation) for each candidate source as unknown parameters in the analysis. However, this adds additional nonlinear free parameters that could burden the analysis and could be unfeasible for some methods. Recently, we described a spatiotemporal Bayesian inference multi-dipole analysis for the MEG/EEG inverse problem. This approach treated the number of dipoles as a free parameter, produced realistic uncertainty estimates using a Markov chain Monte Carlo numerical sampling of the posterior distribution and included a method to reduce the unwanted effects of local minima. In this paper, our spatiotemporal Bayesian inference multi-dipole analysis is extended to incorporate active time range parameters of starting and stopping time points. The properties of this analysis in comparison to the previous one without active time range parameters are demonstrated through extensive studies using both simulated and empirical MEG data.

Action Potentials↗

Incorporating organ movements in inverse planning: assessing dose uncertainties by Bayesian inference.

We present a method to calculate dose uncertainties due to inter-fraction organ movements in fractionated radiotherapy, i.e. in addition to the expectation value of the dose distribution a variance distribution is calculated. To calculate the expectation value of the dose distribution in the presence of organ movements, one estimates a probability distribution of possible patient geometries. The respective variance of the expected dose distribution arises for two reasons: first, the patient is irradiated with a finite number of fractions only and second, the probability distribution of patient geometries has to be estimated from a small number of images and is therefore not exactly known. To quantify the total dose variance, we propose a method that is based on the principle of Bayesian inference. The method is of particular interest when organ motion is incorporated in inverse IMRT planning by means of inverse planning performed on a probability distribution of patient geometries. In order to make this a robust approach, it turns out that the dose variance should be considered (and minimized) in the optimization process. As an application of the presented concept of Bayesian inference, we compare three approaches to inverse planning based on probability distributions that account for an increasing degree of uncertainty. The Bayes theorem further provides a concept to interpolate between patient specific data and population-based knowledge on organ motion which is relevant since the number of CT images of a patient is typically small.

Algorithms↗

Bayesian inference for categorical traits with an application to variance component estimation.

We implemented statistical models of Bayesian inference that included direct and maternal genetic effects for genetic parameter estimation of categorical traits by Gibbs sampling. The estimation errors and variances of estimates of animal versus sire and maternal grandsire models, of linear versus threshold models, of single-trait versus multiple-trait models, and of treating herd-year-season as fixed versus random effects in the model were compared. The results indicated that linear models yielded biased estimates of genetic parameters for categorical traits. The animal model was improper for analysis of categorical traits using a threshold model and the Gibbs sampler. Moreover, linear versus threshold models and animal versus sire-maternal grandsire models resulted in larger Monte Carlo errors and increased auto-correlations among posterior samples. Treating herd-year-seasons as random effects in the threshold models decreased the Monte Carlo error, auto-correlations, and the variances of estimates. Efficiency of the single-trait threshold sire model, as measured by the variance of the estimates, was lower than for a multiple-trait model that included a correlated continuous trait, but both estimates were unbiased. Therefore, the threshold single-trait sire and maternal grandsire model is a feasible alternative to the multiple-trait model for analysis of variance components of categorical traits affected by direct and maternal genetic factors.

Animals↗