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[The distribution of individual radiation doses in liquidators of Chernobyl accident using cytogenetic analysis].

The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with registered doses during 1 year after exposure. The bayesian analysis has been applied for constructing the individual distribution of probability density for biological doses estimated from dicentric and centric ring yields in liquidators. The coincidence of the biological and registered dose has been found in 25% of cases; among the rest persons the documented doses exceeded the biological estimations in 25% of cases and the cytogenetic doses were higher than registered ones in 50% of cases. The total distribution of biological doses was constructed by pooling the individual data in 50 mGy dose intervals. The distribution obtained had the maximum at 300-350 mGy and contained 68% of probability density in the dose range 0-1000 mGy. The probabilistic approach in cohort biodosimetry showed the necessity of corrections in radiogenic risk assessment for Chernobyl liquidators. The advantages of bayesian technique for biodosimetrical treatment of cytogenetic data in conditions of small number of cells scored and low aberration yields induced by low dose irradiation were discussed.

Adult↗

PubMed2003

Utility of the dentin matrix protein 1 (DMP1) gene for resolving mammalian intraordinal phylogenetic relationships.

We sequenced exon 6 of the nuclear dentin matrix protein 1 (DMP1) gene from 19 species of bats (order Chiroptera) to assess the utility of this gene for higher-level phylogenetic studies. Bayesian analysis revealed high support (posterior probabilities >/=0.95) for monophyly of Noctilionoidea (Phyllostomidae, Noctilionidae, and Mormoopidae), all genera and most families examined. Comparison of the phylogenetic information present in DMP1 with mitochondrial rDNA and nuclear RAG2 genes indicated no significant heterogeneity. Thus, we concatenated these three data sets into a single "total evidence" phylogenetic analysis. Combined analysis was congruent with study of RAG2 and combined RAG2 and mtrDNA sequences, but improved support (Bayesian posterior probabilities) for many nodes. Our results indicate that exon 6 of DMP1 is rapidly evolving, able to tolerate non-frame shifting insertion and deletion events, is more variable than RAG2, and provides phylogenetic resolution from the interfamilial to infraclass levels in mammals.

Amino Acid Sequence↗

PubMed2006

Modeling species-habitat relationships with spatially autocorrelated observation data.

Spatial autocorrelation in wildlife observation data arises when extrinsic environmental processes and patterns that influence the spatial distribution of wildlife are themselves spatially structured, or when species are subject to intrinsic population processes, causing contagion or dispersion effects. Territoriality, Allee effects, dispersal limitations, and social clustering are examples of intrinsic processes. Both forms of autocorrelation can violate the assumptions of generalized linear regression models, resulting in biased estimation of model coefficients and diminished predictive performance. Such consequences may be avoided for extrinsic autocorrelation when autocorrelated environmental variables are available for use as model covariates, whereas intrinsic spatial autocorrelation requires an alternative modeling approach. The autologistic model provides an approach suited to the binary observations often obtained in wildlife surveys, but its performance has not been tested across widely varying sampling intensities or strengths of intrinsic spatial structure. Here we use simulated data to test the autologistic model under a range of sampling conditions. The autologistic model obtains better fits and substantially better predictive performance than the standard logistic regression model over the full range of sampling designs and intensities tested. We provide a simple Bayesian implementation of the autologistic model, which until now has not been achieved with standard statistical software alone. A step-by-step procedure is given for characterizing and modeling spatial autocorrelation in binary observation data, along with computer code for fitting autologistic models in WinBUGS, a freeware Bayesian analysis package. This approach avoids normal approximations to the pseudo-likelihood, in contrast to previous Bayesian applications of the autologistic model. We provide a sample application of the autologistic model, fitted to survey data for a gliding marsupial in southeastern Australia.

Bayes Theorem↗

PubMed2007

Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy.

UNLABELLED: Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus and elevated bile acid serum concentrations in late pregnancy. Splicing mutations have been described in the multidrug resistance p-glycoprotein 3 (MDR3, ABCB4) gene in up to 20% of ICP women. Pedigrees studied were not large enough for linkage analysis. Ninety-seven family members of a woman with proven ICP were asked about pruritus in earlier pregnancies, birth complications and symptomatic gallstone disease. The familial cholestasis type 1 (FIC1, ATP8B1) gene, bile salt export pump (BSEP, ABCB11) and MDR3 gene were analyzed in 55 relatives. We identified a dominant mode of inheritance with female restricted expression and a new intronic MDR3 mutation c.3486+5G>A resulting in a 54 bp (3465-3518) inframe deletion via cryptic splicing site activation. Linkage analysis of the ICP trait versus this intragenic MDR3 variant yielded a LOD score of 2.48. A Bayesian analysis involving MDR3, BSEP, FIC1 and an unknown locus gave a posterior probability of >0.9966 in favor of MDR3 as causative ICP locus. During the episode of ICP the median gamma-glutamyl transpeptidase (gamma-GT) activity was 10 U/l (95% CI, 6.9 to 14.7 U/l) in the index woman. Four stillbirths were reported in seven heterozygous women (22 pregnancies) and none in five women (14 pregnancies) without MDR3 mutation. Symptomatic gallstone disease was more prevalent in heterozygous relatives (7/21) than in relatives without the mutation (1/34), (P = 0.00341). CONCLUSION: This study demonstrates that splicing mutations in the MDR3 gene can cause ICP with normal gamma-GT and may be associated with stillbirths and gallstone disease.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2005

Analysis of incidence rates in cluster-randomized trials of interventions against recurrent infections, with an application to trachoma.

A method is developed for the Bayesian analysis of rate ratios of repeated events in matched cluster-randomized trials, and applied to the Flies and Eyes trial against trachoma in The Gambia. A non-mechanistic analysis estimates the incidence rate ratio for insecticide spray, relative to no intervention, as 0.59 (95 per cent credible interval 0.37--0.92), and for latrine provision as 0.67 (0.41--1.01). The method also yields incidence and clearance rate ratios for age. In the Flies and Eyes trial, the former rates are estimated to decrease with age, although no clear pattern is seen in the latter. Using clinical active trachoma as a marker of infection, and net catches to measure fly density, a mechanistic model is developed to estimate the proportion of transmission due to flies. However, it was not possible to estimate this proportion accurately, and a lack of association was noted between the magnitudes of reductions in fly density and in trachoma. The lack of knowledge on the relative importance of different transmission routes is a constraint on the current global programme for the elimination of trachoma.

Adolescent↗

PubMed2004

Identification of a transcriptional profile associated with in vitro invasion in non-small cell lung cancer cell lines.

Although much has been learned about basic mechanisms of cell invasion, the genes whose expression is required for this process by malignant cell lines have remained obscure. We assessed invasion through Matrigel using EGF as a chemoattractant and gene expression profiles using oligonucleotide microarrays for 22 non-small cell lung cancer cell lines. The expression of 22 genes were significantly correlated (p < 0.001) with the measured invasion index. Cluster analysis demonstrated that gene expression profiles classify the cell lines into low and high invasive subgroups. Considering invasiveness as a dichotomous variable, Bayesian analysis was used to identify genes that have the highest probability of being differentially expressed between the high and low invasion groups. This analysis identified 16 genes whose expression was associated with invasiveness. "Leave one out" cross validation was 91% accurate. Nine genes were identified in both correlation and Bayesian analyses. Seven of the nine genes were negatively associated with invasion and four of those genes are plasma membrane proteins. The two genes with the highest inverse association with invasion, TACSTD1 and CLDN3, are involved with cell adhesion and cell-cell interactions, respectively. Interestingly, the gene with the highest positive association with invasion, SERPINE1 (PAI-1), is a protease inhibitor. These and the other genes identified by both analyses represent targets for further study to assess their importance in non-small cell lung cancer invasion and metastasis.

Adenocarcinoma↗

PubMed2002

Profiling nursing homes using Bayesian hierarchical modeling.

OBJECTIVES: New methods developed to improve the statistical basis of provider profiling may be particularly applicable to nursing homes. We examine the use of Bayesian hierarchical modeling in profiling nursing homes on their rate of pressure ulcer development. DESIGN: Observational study using Minimum Data Set data from 1997 and 1998. SETTING: A for-profit nursing home chain. PARTICIPANTS: Residents of 108 nursing homes who were without a pressure ulcer on an index assessment. MEASUREMENTS: Nursing homes were compared on their performance on risk-adjusted rates of pressure ulcer development calculated using standard statistical techniques and Bayesian hierarchical modeling. RESULTS: Bayesian estimates of nursing home performance differed considerably from rates calculated using standard statistical techniques. The range of risk-adjusted rates among nursing homes was 0% to 14.3% using standard methods and 1.0% to 4.8% using Bayesian analysis. Fifteen nursing homes were designated as outliers based on their z scores, and two were outliers using Bayesian modeling. Only one nursing home had greater than a 50% probability of having a true rate of ulcer development exceeding 4%. CONCLUSIONS: Bayesian hierarchical modeling can be successfully applied to the problem of profiling nursing homes. Results obtained from Bayesian modeling are different from those obtained using standard statistical techniques. The continued evaluation and application of this new methodology in nursing homes may ensure that consumers and providers have the most accurate information regarding performance.

Bayes Theorem↗

PubMed1997

Bayesian procedures for discriminating among hypotheses with discrete distributions: inheritance in the tetraploid Astilbe biternata.

Discrimination between disomic and tetrasomic inheritance aids in determining whether tetraploids originated by allotetraploidy or autotetraploidy, respectively. Past assessments of inheritance in tetraploids have used analyses whereby each inheritance hypothesis is tested independently. I present a Bayesian analysis that is appropriate for discriminating among several inheritance hypotheses and can be used in any case where hypotheses are defined by discrete distributions. The Bayesian approach incorporates prior knowledge of the probability of occurrence of disomic and tetrasomic hypotheses so that the results of the analysis are not biased by the fact that there is a single tetrasomic hypothesis and multiple disomic hypotheses. This analysis is used to interpret data from crosses in the tetraploid Astilbe biternata, a herbaceous plant native to the southern Appalachians. The progeny ratios from all crosses favored the hypothesis of disomic inheritance at both the PGM and slow-PGI loci. These results support earlier cytogenetic evidence for the allotetraploid origin of Astilbe biternata.

Alleles↗

PubMed2006

The phylogeny of rodent malaria parasites: simultaneous analysis across three genomes.

Species of Plasmodium that naturally infect wild rodents but can also be maintained in laboratory mice have long been used as model systems in which to study the biology of malaria parasites. Several of these rodent parasites are now providing useful genomic comparisons to those species that cause malaria in humans. Here we examined the phylogenetic relationships of 19 strains of rodent malaria parasites including four species native to African thicket rats (Plasmodium berghei, Plasmodium chabaudi, Plasmodium vinckei, and Plasmodium yoelii) and one from a porcupine (Plasmodium atheruri) using DNA sequence data collected from seven genes from each of the three parasite genomes. These included the nuclear dihydrofolate reductase gene and a cysteine protease gene, mitochondrial cytochrome b and cytochrome oxidase I genes, and the elongation factor tufA, caseinolytic protease C, and "open reading frame 470" genes from the apicoplast genome, for a combined total of 5049 nucleotides. Using simultaneous analysis, a method of combining each of the gene partitions into a super-matrix, two equally parsimonious trees were recovered. Bayesian analysis of the dataset produced the same topology. The basic species groups were well supported, with the exception of the placement of P. atheruri within the P. vinckei clade. Named subspecies showed a wide array of genetic differentiation, but fell into monophyletic groups.

Animals↗

PubMed2002

Application of Bayesian decomposition for analysing microarray data.

MOTIVATION: Microarray and gene chip technology provide high throughput tools for measuring gene expression levels in a variety of circumstances, including cellular response to drug treatment, cellular growth and development, tumorigenesis, among many other processes. In order to interpret the large data sets generated in experiments, data analysis techniques that consider biological knowledge during analysis will be extremely useful. We present here results showing the application of such a tool to expression data from yeast cell cycle experiments. RESULTS: Originally developed for spectroscopic analysis, Bayesian Decomposition (BD) includes two features which make it useful for microarray data analysis: the ability to assign genes to multiple coexpression groups and the ability to encode biological knowledge into the system. Here we demonstrate the ability of the algorithm to provide insight into the yeast cell cycle, including identification of five temporal patterns tied to cell cycle phases as well as the identification of a pattern tied to an approximately 40 min cell cycle oscillator. The genes are simultaneously assigned to the patterns, including partial assignment to multiple patterns when this is required to explain the expression profile. AVAILABILITY: The application is available free to academic users under a material transfer agreement. Go to http://bioinformatics.fccc.edu/ for more details.

Algorithms↗

PubMed2003

Reanalysis of Murphy et al.'s data gives various mammalian phylogenies and suggests overcredibility of Bayesian trees.

Murphy and colleagues reported that the mammalian phylogeny was resolved by Bayesian phylogenetics. However, the DNA sequences they used had many alignment gaps and undetermined nucleotide sites. We therefore reanalyzed their data by minimizing unshared nucleotide sites and retaining as many species as possible (13 species). In constructing phylogenetic trees, we used the Bayesian, maximum likelihood (ML), maximum parsimony (MP), and neighbor-joining (NJ) methods with different substitution models. These trees were constructed by using both protein and DNA sequences. The results showed that the posterior probabilities for Bayesian trees were generally much higher than the bootstrap values for ML, MP, and NJ trees. Two different Bayesian topologies for the same set of species were sometimes supported by high posterior probabilities, implying that two different topologies can be judged to be correct by Bayesian phylogenetics. This suggests that the posterior probability in Bayesian analysis can be excessively high as an indication of statistical confidence and therefore Murphy et al.'s tree, which largely depends on Bayesian posterior probability, may not be correct.

Animals↗

PubMed2003

Population genetic variation in genome-wide gene expression.

Evolutionary biologists seek to understand which traits display variation, are heritable, and influence differential reproduction, because such traits respond to natural selection and underlie organic evolution. Selection acts upon individual differences within a population. Whether individual differences within a natural population include variation in gene expression levels has not yet been addressed on a genome-wide scale. Here we use DNA microarray technology for measuring comparative gene expression and a refined statistical analysis for the purpose of comparing gene expression levels in natural isolates of the wine yeast Saccharomyces cerevisiae. A method for the Bayesian analysis of gene expression levels is used to compare four natural isolates of S. cerevisiae from Montalcino, Italy. Widespread variation in amino acid metabolism, sulfur assimilation and processing, and protein degradation-primarily consisting of differences in expression level smaller than a factor of 2-is demonstrated. Genetic variation in gene expression among isolates from a natural population is present on a genomic scale. It remains to be determined what role differential gene expression may play in adaptation to new or changing environments.

DNA Transposable Elements↗

PubMed1995

Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease. What physicians know, and what they should know.

BACKGROUND: Published studies now show a clear association between Alzheimer's disease (AD) and the apolipoprotein E epsilon 4 allele (APOE* epsilon 4). The clinical value of this information to estimate a healthy individual's lifetime risk of AD has not been well delineated. Physicians dealing with AD may not know either the lifetime risk of developing AD or the effect of the APOE genotype on this risk. Because the lifetime risk of AD depends in part on life expectancy, and available figures on APOE are not population based, a computation is necessary to derive risk estimates useful to physicians. OBJECTIVES: To estimate the lifetime risk of AD and the effect of APOE genotype information on that risk and to assess the knowledge of these risks among physicians who manage patients with dementia. DESIGN: Estimation of risk of AD and survey of physician awareness. The lifetime risk of developing AD without APOE genotype information was first computed for 65-year-olds from existing epidemiologic studies of age-related AD incidence and an actuarial life-table analysis. Using this computed a priori risk of AD and published studies of APOE genotypes in individuals with and without AD, we used a Bayesian analysis to determine the risk of developing AD, with and without an APOE* epsilon 4 allele, for unaffected 65-year-olds. To assess physician knowledge of the lifetime risk of AD and the effect of APOE genotyping on the risk, 50 neurologists, internists, geriatricians, geriatric psychiatrists, and family physicians who manage patients with dementia were randomly selected to participate in a questionnaire-driven telephone survey. RESULTS: In a person with no family history of AD, the epidemiologic/actuarial lifetime risk of AD is approximately 15%. Based on a Bayesian calculation and published APOE data, the lifetime risk of AD is 29% for individuals with one APOE* epsilon 4 allele and it is 9% if no APOE* epsilon 4 allele is present. Physician awareness survey results were as follows: 42% of physicians correctly estimated the approximate lifetime risk of AD; of these, only one third were moderately sure of their response. Only three physicians correctly estimated the change in risk given the APOE* epsilon 4 genotype; only one of these was at least moderately sure. CONCLUSIONS: Determining the APOE* epsilon 4 status of healthy adults with no family history of AD approximately doubles (for the epsilon 4 allele) or reduces by 40% (for the non-epsilon 4 allele) the uninformed lifetime risk of developing AD. Even with an APOE* epsilon 4 allele, the lifetime risk remains below 30%. Most physicians managing patients with AD do not know the lifetime risk of AD, and very few know how APOE* epsilon 4 status modifies the risk. These clinically relevant risk figures should be more widely disseminated among physicians.

Actuarial Analysis↗

PubMed1990

Two-locus linkage analysis using recombinant inbred strains and Bayes' theorem.

Recombinant inbred (RI) strains are useful in linkage analysis and gene mapping. The currently available statistical tests of linkage using data derived from the study of RI strains, including a previous Bayesian analysis, have not been stringent enough guides for conclusions about linkage. In this paper, the probability of linkage was estimated using Bayes' theorem. Tables are presented that give the probability of linkage in sets of up to 30 RI strains and the critical values of i (the number of recombinants) in sets of up to 100 RI strains. Several means of increasing the power of RI strains in linkage analysis are discussed.

Animals↗

PubMed2005

Hierarchical models for the probabilities of conception.

In the last thirty years, there has been considerable interest in finding better models to fit data for probabilities of conception. An important early model was proposed by Barrett and Marshall (1969) and extended by Schwartz, MacDonald and Heuchel (1980). Recently, researchers have further extended these models by adding covariates. However, the increasingly complicated models are challenging to analyze with frequentist methods such as the EM algorithm. Bayesian models are more feasible, and the computation can be done via Markov chain Monte Carlo (MCMC). We consider a Bayesian model with an effect for protected intercourse to analyze data from the California Women's Reproductive Health Study and assess the effects of water contaminants and hormones. There are two main contributions in the paper. (1) For protected intercourse, we propose modeling the ratios of daily conception probabilities with protected intercourse to corresponding daily conception probabilities with unprotected intercourse. Due to the small sample size of our data set, we assume the ratios are the same for each day but unknown. (2) We consider Bayesian analysis under a unimodality assumption where the probabilities of conception increase before ovulation and decrease after ovulation. Gibbs sampling is used for finding the Bayesian estimates. There is some evidence that the two covariates affect fecundability.

Bayes Theorem↗

PubMed2003

Single origin of Malagasy Carnivora from an African ancestor.

The Carnivora are one of only four orders of terrestrial mammals living in Madagascar today. All four (carnivorans, primates, rodents and lipotyphlan insectivores) are placental mammals with limited means for dispersal, yet they occur on a large island that has been surrounded by a formidable oceanic barrier for at least 88 million years, predating the age of origin for any of these groups. Even so, as many as four colonizations of Madagascar have been proposed for the Carnivora alone. The mystery of the island's mammalian origins is confounded by its poor Tertiary fossil record, which leaves us with no direct means for estimating dates of initial diversification. Here we use a multi-gene phylogenetic analysis to show that Malagasy carnivorans are monophyletic and thus the product of a single colonization of Madagascar by an African ancestor. Furthermore, a bayesian analysis of divergence ages for Malagasy carnivorans and lemuriforms indicates that their respective colonizations were temporally separated by tens of millions of years. We therefore conclude that a single event, such as vicariance or common dispersal, cannot explain the presence of both groups in Madagascar.

Africa↗

PubMed2006

Recurrent replacement of mtDNA and cryptic hybridization between two sibling bat species Myotis myotis and Myotis blythii.

The two sibling bat species Myotis myotis and Myotis blythii occur in sympatry over wide areas of Southern and Central Europe. Morphological, ecological and previous genetic evidence supported the view that the two species constitute two well-differentiated groups, but recent phylogenetic analyses have shown that the two species share some mtDNA haplotypes when they occur in sympatry. In order to see whether some genetic exchange has occurred between the two species, we sequenced a highly variable segment of the mitochondrial control region in both species living in sympatry and in allopatry. We also analysed the nuclear diversity of 160 individuals of both species found in two mixed nursery colonies located north and south of the Alps. MtDNA analysis confirmed that European M. blythii share multiple, identical or very similar haplotypes with M. myotis. Since allopatric Asian M. blythii presents mtDNA sequences that are very divergent from those of the two species found in Europe, we postulate that the mitochondrial genome of the European M. blythii has been replaced by that of M. myotis. The analysis of nuclear diversity shows a strikingly different pattern, as both species are well differentiated within mixed nursery colonies (F(ST) = 0.18). However, a Bayesian analysis of admixture reveals that the hybrids can be frequently observed, as about 25% of sampled M. blythii show introgressed genes of M. myotis origin. In contrast, less than 4% of the M. myotis analysed were classified as non-parental genotypes, revealing an asymmetry in the pattern of hybridization between the two species. These results show that the two species can interbreed and that the hybridization is still ongoing in the areas of sympatry. The persistence of well-differentiated nuclear gene pools, in spite of an apparent replacement of mitochondrial genome in European M. blythii by that of M. myotis, is best explained by a series of introgression events having occurred repeatedly during the recent colonization of Europe by M. blythii from Asia. The sharp contrast obtained from the analysis of mitochondrial and nuclear markers further points to the need to cautiously interpret results based on a single class of genetic markers.

Animals↗

PubMed2005

A Bayesian approach to modeling dynamic effective connectivity with fMRI data.

A state-space modeling approach for examining dynamic relationship between multiple brain regions was proposed in Ho, Ombao and Shumway (Ho, M.R., Ombao, H., Shumway, R., 2005. A State-Space Approach to Modelling Brain Dynamics to Appear in Statistica Sinica). Their approach assumed that the quantity representing the influence of one neuronal system over another, or effective connectivity, is time-invariant. However, more and more empirical evidence suggests that the connectivity between brain areas may be dynamic which calls for temporal modeling of effective connectivity. A Bayesian approach is proposed to solve this problem in this paper. Our approach first decomposes the observed time series into measurement error and the BOLD (blood oxygenation level-dependent) signals. To capture the complexities of the dynamic processes in the brain, region-specific activations are subsequently modeled, as a linear function of the BOLD signals history at other brain regions. The coefficients in these linear functions represent effective connectivity between the regions under consideration. They are further assumed to follow a random walk process so to characterize the dynamic nature of brain connectivity. We also consider the temporal dependence that may be present in the measurement errors. ML-II method (Berger, J.O., 1985. Statistical Decision Theory and Bayesian Analysis (2nd ed.). Springer, New York) was employed to estimate the hyperparameters in the model and Bayes factor was used to compare among competing models. Statistical inference of the effective connectivity coefficients was based on their posterior distributions and the corresponding Bayesian credible regions (Carlin, B.P., Louis, T.A., 2000. Bayes and Empirical Bayes Methods for Data Analysis (2nd ed.). Chapman and Hall, Boca Raton). The proposed method was applied to a functional magnetic resonance imaging data set and results support the theory of attentional control network and demonstrate that this network is dynamic in nature.

Attention↗