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Results for “Bayesian analysis”

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PubMed2004

A Bayesian statistical analysis of human T-cell lymphotropic virus evolutionary rates.

HTLV is a genetically-stable retrovirus that is considered to have evolved partly in concert with human migrations. Its rate of evolution is low and therefore, difficult to estimate reliably. In the first part of this study, we provide an improved estimate of HTLV evolutionary rate using anthropological calibration of phylogenetic nodes. We investigate two different anthropological calibrations using a Bayesian method that implements a relaxed molecular clock model and can combine data from multiple genes. The analysis shows that the two calibrations are compatible. In the second part, we develop a Bayesian statistical model to combine and compare the anthropology-based estimates of evolutionary rate with a rate recently calculated using pedigree data from vertically HTLV-infected families. We compare the statistical power of the two estimates and show that the current pedigree estimate, although resulting in considerably higher evolutionary rates, is too statistically weak to warrant a re-examination of the commonly used anthropology-based estimates. Statistical uncertainty burdens HTLV rate estimates based on both anthropological calibrations and on pedigree data; the former method rests on an untested assumption, whilst that latter is affected by small sample sizes.

Bayes Theorem↗

PubMed1997

Bayesian phylogenetic inference using DNA sequences: a Markov Chain Monte Carlo Method.

An improved Bayesian method is presented for estimating phylogenetic trees using DNA sequence data. The birth-death process with species sampling is used to specify the prior distribution of phylogenies and ancestral speciation times, and the posterior probabilities of phylogenies are used to estimate the maximum posterior probability (MAP) tree. Monte Carlo integration is used to integrate over the ancestral speciation times for particular trees. A Markov Chain Monte Carlo method is used to generate the set of trees with the highest posterior probabilities. Methods are described for an empirical Bayesian analysis, in which estimates of the speciation and extinction rates are used in calculating the posterior probabilities, and a hierarchical Bayesian analysis, in which these parameters are removed from the model by an additional integration. The Markov Chain Monte Carlo method avoids the requirement of our earlier method for calculating MAP trees to sum over all possible topologies (which limited the number of taxa in an analysis to about five). The methods are applied to analyze DNA sequences for nine species of primates, and the MAP tree, which is identical to a maximum-likelihood estimate of topology, has a probability of approximately 95%.

Algorithms↗

PubMed2003

Bayesian deconvolution analysis of pulsatile hormone concentration profiles.

Many hormones are secreted into the circulatory system in a pulsatile manner and are cleared exponentially. The most common method of analyzing these systems is to deconvolve the hormone concentration into a secretion function and a clearance function. Accurate estimation of the model parameters depends on the number and location of the secretion pulses. To date, deconvolution analysis assumes the number and approximate location of these pulses are known a priori. In this article, we present a novel Bayesian approach to deconvolution that jointly models the number of pulses along with all other model parameters. Our method stochastically searches for the secretion pulses. This is accomplished by viewing the set of parameters that define the pulses as a point process. Pulses are determined by a birth-death process which is embedded in Markov chain Monte Carlo algorithm. This idea originated with Stephens (2000, Annals of Statistics 28, 40-74) in the context of finite mixture model density estimation, where the number of mixture components is unknown. There are several advantages that our model enjoys over the traditional frequentist approaches. These advantages are highlighted with four datasets consisting of serum concentration levels of luteinizing hormone obtained from ovariectomized ewes.

Animals↗

PubMed2006

Combined mitochondrial and nuclear sequences support the monophyly of forcipulatacean sea stars.

Previous molecular phylogenetic analyses of forcipulatacean sea stars (Echinodermata: Asteroidea) have reconstructed a non-monophyletic order Forcipulatida, provided that two or more forcipulate families are included. This result could mean that one or more assumptions of the reconstruction method was violated, or else the traditional classification could be erroneous. The present molecular phylogenetic analysis included 12 non-forcipulatacean and 39 forcipulatacean sea stars, with multiple representatives of all but one of the forcipulate families and/or subfamilies. Bayesian analysis of approximately 4.2kb of sequence data representing seven partitions (nuclear 18S rRNA and 28S rRNA, mitochondrial 12S rRNA, 16S rRNA, 5 tRNAs and cytochrome oxidase I with first and second codon positions analyzed separately from third codon positions) recovered a consensus tree with three well-supported clades (78%-100% bootstrap support) that corresponded at least approximately to traditional taxonomic ranks: the superorder Forcipulatacea (Forcipulatida + Brisingida) + Pteraster, the Brisingida/Brisingidae and Asteriidae + Rathbunaster + Pycnopodia. When a molecular clock was enforced, the partitioned Bayesian analysis recovered the traditional Forcipulatacea. Five of six genera represented by two or more species were monophyletic with 100% bootstrap support. Most of the traditional subfamilial and familial groupings within the Forcipulatida were either unresolved or non-monophyletic. The separate partitions differed considerably in estimates of model parameters, mainly between nuclear sequences (with high GC content, low rates of sequence substitution and high transition/transversion rate ratios) and mitochondrial sequences.

Animals↗

PubMed2005

Bayesian phylogenetic analysis reveals two-domain topology of S-adenosylhomocysteine hydrolase protein sequences.

S-Adenosylhomocysteine hydrolase (SahH) is involved in the degradation of the compound which inhibits methylation reactions. Using a Bayesian approach and other methods, we reconstructed a phylogenetic tree of amino acid sequences of this protein originating from all three major domains of living organisms. The SahH sequences formed two major branches: one composed mainly of Archaea and the other of eukaryotes and majority of bacteria, clearly contradicting the three-domain topology shown by small subunit rRNA gene. This topology suggests the occurrence of lateral transfer of this gene between the domains. Poor resolution of eukaryotes and bacteria excluded an ultimate conclusion in which out of the two domains this gene appeared first, however, the congruence of the secondary branches with SS rRNA and/or concatenated ribosomal protein datasets phylogenies suggested an "early" acquisition by some bacterial and eukaryotic phyla. Similarly, the branching pattern of Archaea reflected the phylogenies shown by SS rRNA and ribosomal proteins. SahH is widespread in Eucarya, albeit, due to reductive evolution, it is missing in the intracellular parasite Encephalitozoon cuniculi. On the other hand, the lack of affinity to the sequences from the alpha-Proteobacteria and cyanobacteria excludes a possibility of its acquisition in the course of mitochondrial or chloroplast endosymbioses. Unlike Archaea, most bacteria carry MTA/SAH nucleosidase, an enzyme involved also in metabolism of methylthioadenosine. However, the double function of MTA/SAH nucleosidase may be a barrier to ensure the efficient degradation of S-adenosylhomocysteine, specially when the intensity of methylation processes is high. This would explain the presence of S-adenosylhomocysteine hydrolase in the bacteria that have more complex metabolism. On the other hand, majority of obligate pathogenic bacteria due to simpler metabolism rely entirely on MTA/SAH nucleosidase. This could explain the observed phenetic pattern in which bacteria with larger (>6 Mb-million base pairs) genomes carry SAH hydrolase, whereas bacteria that have undergone reductive evolution usually carry MTA/SAH nucleosidase. This suggests that the presence or acquisition of S-adenosylhomocysteine hydrolase in bacteria may predispose towards higher metabolic, and in consequence, higher genomic complexity. The good examples are the phototrophic bacteria all of which carry this gene, however, the SahH phylogeny shows lack of congruence with SSU rRNA and photosyntethic genes, implying that the acquisition was independent and presumably preceded the acquisition of photosyntethic genes. The majority of cyanobacteria acquired this gene from Archaea, however, in some species the sahH gene was replaced by a copy from the beta- or gamma-Proteobacteria.

Adenosylhomocysteinase↗

PubMed2006

The phylogeny of early eureptiles: comparing parsimony and Bayesian approaches in the investigation of a basal fossil clade.

For the first time the phylogenetic relationships of early eureptiles, consisting of captorhinids, diapsids, and protorothyridids, are investigated in a modern phylogenetic context using both parsimony and Bayesian approaches. Ninety parsimony-informative characters and 25 taxa were included in the analyses. The Bayesian analysis was run with and without a gamma-shape parameter allowing for variable rates across characters. In addition, we ran two more Bayesian analyses that included 42 autapomorphies and thus parsimony-uninformative characters in order to test the effect of variable branch lengths. The different analyses largely converged to the same topology, suggesting that the "protorothyridid" Coelostegus is the sister taxon of all other eureptiles and that the remaining "protorothyridids" are paraphyletic. Also, there is a close relationship between diapsids and Anthracodromeus, Cephalerpeton, and Protorothyris, a grouping of Thuringothyris with captorhinids, and a variable position of the "protorothyridids" Brouffia, Hylonomus, and Paleothyris. The lack of resolution in some parts of the tree might be due to "hard polytomies" and short divergence times between the respective taxa. The tree topology is consistent with the hypothesis that the temporal fenestrations of diapsid reptiles appear to be the consequence of a more lightly built skeleton, indicating a significant ecological shift in the early stages of diapsid evolution. Bayesian analysis is a very useful additional approach in studies of fossil taxa in which more traditional statistical support like the bootstrap is often weak. However, the exclusive use of the Mk model appears suitable only if autapomorphic characters are included, whereas the Mk+gamma model performed well with or without autapomorphies.

Animals↗

PubMed1994

Single anticardiolipin measurement in the routine management of patients with systemic lupus erythematosus.

OBJECTIVE: To examine the usefulness of a single measurement of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) in routine clinical practice. METHODS: All 127 patients with SLE currently followed by our rheumatology unit had an aCL measurement on routine clinic review. Their charts were then reviewed for specific disease manifestations. Basic statistical correlations of the aCL result and the specific disease manifestations were performed, and the clinical utility of the aCL test assessed using Bayesian analysis. RESULTS: aCL was positive (> 2 SD) in 24% and was associated with recurrent fetal loss, thrombosis, cerebrovascular disease, livedo reticularis and digital infarcts. Bayesian analysis showed that a single positive aCL test increased the relative and absolute risk of all the above complications. The criterion of aCL positivity as > 15 units (2 SD) was associated with the highest relative risk. CONCLUSION: A single positive aCL test in routine management of SLE is a useful predictor of important clinical events.

Adult↗

PubMed1997

Bayesian interim analysis of phase II cancer clinical trials.

Many popular sequential phase II clinical trial designs optimize some criterion subject to constraints on the error probabilities at null and alternative values of the response rate. Such designs may forfeit optimality if one fails to conduct analyses strictly according to plan. Moreover, a decision, say, to accept the experimental therapy at one interim analysis does not necessarily imply the same degree of evidence as the same decision when made at another analysis. I propose an alternative design that bases decisions on the ability of the data to persuade either a sceptic or an enthusiast. My standard of evidence, called the persuasion probability, is based on the Bayesian posterior probability that the experimental treatment is superior to the standard. The design calls for termination at any interim analysis at which an observed persuasion probability exceeds its critical value. I investigate the standards of evidence implied by some frequentist procedures and calculate frequentist properties of persuasion-probability designs.

Acute Disease↗

PubMed1995

Clinical reasoning about new symptoms despite preexisting disease: sources of error and order effects.

BACKGROUND: Previous work that studied the evaluation of new, atypical symptoms in patients with preexisting diseases indicated that physicians largely ignored the past medical history and therefore erred in their diagnoses, when compared to a Bayesian analysis. Other studies have shown that the order in which information is presented to a decision maker can affect the inferences drawn, again contrary to a Bayesian standard. OBJECTIVES: The aim of the study was to investigate the source of disparity between clinical judgment and Bayesian analysis and to investigate the effect of alternative orders of presenting information on diagnostic conclusions. METHODS: Two groups of family physicians received a written clinical scenario. One group was given the past medical history before the history of present illness, the physical exam, and the laboratory data. The second group learned about the past medical history after all other clinical information had been presented. Judgments of test accuracy and probably diagnosis were collected at several points to identify the source of any diagnostic error. RESULTS: For both groups, the major source of error was in estimating the prior probability of disease, not in estimating the accuracy of a diagnostic test or updating opinions following receipt of test results. Although both groups of physicians received the same information, they came to markedly different conclusions about the most likely diagnosis. The group given the past medical history at the beginning of the scenario considered this information much less significant than did the group who received it at the end. CONCLUSIONS: Family physicians deviate from a Bayesian standard of reasoning by wrongly specifying prior probabilities and by being influenced by the order in which clinical information is presented.

Bayes Theorem↗

PubMedDate not supplied

Designing for nonparametric Bayesian survival analysis using historical controls.

This paper gives a method for choosing the number of patients N0 out of N available patients to be randomized to current controls om a two-arm study when comparison of nonparametric survival curves is the anticipated method of data analysis. The criterion imposed is that of choosing N0 to minimize the posterior variance of the difference between the current control and experimental survival curves. A nonparametric Bayesian argument incorporating the survival curve of available historical controls establishes the criterion. Formulas and tables which facilitate this computation are presented.

Bayes Theorem↗

PubMed2004

Individual organisms as units of analysis: Bayesian-clustering alternatives in population genetics.

Population genetic analyses traditionally focus on the frequencies of alleles or genotypes in 'populations' that are delimited a priori. However, there are potential drawbacks of amalgamating genetic data into such composite attributes of assemblages of specimens: genetic information on individual specimens is lost or submerged as an inherent part of the analysis. A potential also exists for circular reasoning when a population's initial identification and subsequent genetic characterization are coupled. In principle, these problems are circumvented by some newer methods of population identification and individual assignment based on statistical clustering of specimen genotypes. Here we evaluate a recent method in this genre--Bayesian clustering--using four genotypic data sets involving different types of molecular markers in non-model organisms from nature. As expected, measures of population genetic structure (F(ST) and phiST) tended to be significantly greater in Bayesian a posteriori data treatments than in analyses where populations were delimited a priori. In the four biological contexts examined, which involved both geographic population structures and hybrid zones, Bayesian clustering was able to recover differentiated populations, and Bayesian assignments were able to identify likely population sources of specific individuals.

Animals↗

PubMed1989

Bayesian regression analysis of non-steady-state phenytoin concentrations: evaluation of predictive performance.

Michaelis-Menten saturable pharmacokinetics confound the determination of appropriate phenytoin maintenance doses. This study retrospectively evaluated the performance of an IBM-PC/XT computer program applying Bayesian regression to the "explicit solution to the Michaelis-Menten equation." Zero to five non-steady-state phenytoin serum concentrations were used to predict either non-steady-state concentrations at least 10 days in the future (n = 49) or steady-state concentrations (n = 20). Non-steady-state concentration prediction precision (% mean absolute error) using 0-5 non-steady-state feedbacks was 137%, 62%, 39%, 31%, 25%, and 15%, respectively, and steady-state concentration prediction precision was 446%, 47%, 50%, 44%, 21%, and 13%, respectively. Elimination of subjects receiving concurrent drugs known to induce phenytoin metabolism significantly improved predictions based on population priors; however, performance improvements were not apparent after two serum level feedbacks. The program provided clinically acceptable predictions with four or more feedbacks. Refinement of population parameters and optimal sampling times should further improve performance.

Aged↗

PubMed2003

Phylogenetics of advanced snakes (Caenophidia) based on four mitochondrial genes.

Phylogenetic relationships among advanced snakes (Acrochordus + Colubroidea = Caenophidia) and the position of the genus Acrochordus relative to colubroid taxa are contentious. These concerns were investigated by phylogenetic analysis of fragments from four mitochondrial genes representing 62 caenophidian genera and 5 noncaenophidian taxa. Four methods of phylogeny reconstruction were applied: matrix representation with parsimony (MRP) supertree consensus, maximum parsimony, maximum likelihood, and Bayesian analysis. Because of incomplete sampling, extensive missing data were inherent in this study. Analyses of individual genes retrieved roughly the same clades, but branching order varied greatly between gene trees, and nodal support was poor. Trees generated from combined data sets using maximum parsimony, maximum likelihood, and Bayesian analysis had medium to low nodal support but were largely congruent with each other and with MRP supertrees. Conclusions about caenophidian relationships were based on these combined analyses. The Xenoderminae, Viperidae, Pareatinae, Psammophiinae, Pseudoxyrophiinae, Homalopsinae, Natricinae, Xenodontinae, and Colubrinae (redefined) emerged as monophyletic, whereas Lamprophiinae, Atractaspididae, and Elapidae were not in one or more topologies. A clade comprising Acrochordus and Xenoderminae branched closest to the root, and when Acrochordus was assessed in relation to a colubroid subsample and all five noncaenophidians, it remained associated with the Colubroidea. Thus, Acrochordus + Xenoderminae appears to be the sister group to the Colubroidea, and Xenoderminae should be excluded from Colubroidea. Within Colubroidea, Viperidae was the most basal clade. Other relationships appearing in all final topologies were (1) a clade comprising Psammophiinae, Lamprophiinae, Atractaspididae, Pseudoxyrophiinae, and Elapidae, within which the latter four taxa formed a subclade, and (2) a clade comprising Colubrinae, Natricinae, and Xenodontinae, within which the latter two taxa formed a subclade. Pareatinae and Homalopsinae were the most unstable clades.

Animals↗

PubMed1997

Advances in statistical methods to map quantitative trait loci in outbred populations.

Statistical methods to map quantitative trait loci (QTL) in outbred populations are reviewed, extensions and applications to human and plant genetic data are indicated, and areas for further research are identified. Simple and computationally inexpensive methods include (multiple) linear regression of phenotype on marker genotypes and regression of squared phenotypic differences among relative pairs on estimated proportions of identity-by-descent at a locus. These methods are less suited for genetic parameter estimation in outbred populations but allow the determination of test statistic distributions via simulation or data permutation; however, further inferences including confidence intervals of QTL location require the use of Monte Carlo or bootstrap sampling techniques. A method which is intermediate in computational requirements is residual maximum likelihood (REML) with a covariance matrix of random QTL effects conditional on information from multiple linked markers. Testing for the number of QTLs on a chromosome is difficult in a classical framework. The computationally most demanding methods are maximum likelihood and Bayesian analysis, which take account of the distribution of multilocus marker-QTL genotypes on a pedigree and permit investigators to fit different models of variation at the QTL. The Bayesian analysis includes the number of QTLs on a chromosome as an unknown.

Bayes Theorem↗

PubMed2006

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Bayes Theorem↗

PubMed2006

Vision as Bayesian inference: analysis by synthesis?

We argue that the study of human vision should be aimed at determining how humans perform natural tasks with natural images. Attempts to understand the phenomenology of vision from artificial stimuli, although worthwhile as a starting point, can lead to faulty generalizations about visual systems, because of the enormous complexity of natural images. Dealing with this complexity is daunting, but Bayesian inference on structured probability distributions offers the ability to design theories of vision that can deal with the complexity of natural images, and that use 'analysis by synthesis' strategies with intriguing similarities to the brain. We examine these strategies using recent examples from computer vision, and outline some important implications for cognitive science.

Algorithms↗

PubMed2006

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↗

PubMed1995

Quantitative assessment of myocardial ultrasound tissue characterization through receiver operating characteristic analysis of Bayesian classifiers.

OBJECTIVES: This work proposes a self-consistent assessment methodology for quantitative evaluation of any combination of diagnostic features, with the immediate goal of quantitatively assessing the discriminating power in diabetic patients of features derived from ultrasound backscatter from myocardium. BACKGROUND: Four features from analysis of left ventricular myocardial ultrasound backscatter have previously been shown to be sensitive to potentially cardiomyopathic changes in patients with insulin-dependent diabetes mellitus who have no overt heart disease. The measured features were significantly different between such patients and normal control subjects, as well as among groups of such patients with and without systemic complications of the disease. The quantitative discriminating potential of the features was not assessed. METHODS: Multivariate classifier functions were constructed and analyzed by using the methodology of the receiver operating characteristic curve, which allows quantitative assessment of the discriminating power of these features, alone or in combination. The area under the receiver operating characteristic curve--the true positive rate averaged over all false positive rates--was used as a summary measure of performance. RESULTS: In distinguishing patients with insulin-dependent diabetes mellitus from normal control subjects, the most discriminating combination of ultrasound features for the detection of such changes in these patients yielded receiver operating characteristic curves with area measures of approximately 0.80; for such patients with retinopathy the measure increased to 0.90. This performance is comparable to that of many commonly used diagnostic tests. CONCLUSIONS: A self-consistent set of evaluation methodologies has quantitatively demonstrated the sensitivity of four ultrasound backscatter features to otherwise latent changes in myocardial structure that accompany the evolution of insulin-dependent diabetes mellitus. The results are remarkable in themselves and suggest the potential of the features for the general field of cardiac ultrasound tissue characterization.

Bayes Theorem↗