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Results for “Bayesian analysis”

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PubMed1996

Medical causation analysis heuristics.

Medical causation analysis determines whether or not a specific patient's illness is the result of a work site or an environmental exposure. In the past, this has been conducted implicitly with little analysis of the process per se. Our review suggests that there are several distinct heuristics that may be utilized; these include probability-based models, application of group-based data (epidemiology) to individuals, Bayesian analysis, a priori assumptions about which conclusions are better, and others. Some methods consider only work causes, whereas others explicitly consider alternative explanations. There are considerable differences among the methods in process, outcome, and fundamental assumptions. Formal assessment of the medical causation analysis process can provide insight and may ultimately lead to its standardization and improvement.

Causality↗

PubMed2004

Probabilistic independent component analysis for functional magnetic resonance imaging.

We present an integrated approach to probabilistic independent component analysis (ICA) for functional MRI (FMRI) data that allows for nonsquare mixing in the presence of Gaussian noise. In order to avoid overfitting, we employ objective estimation of the amount of Gaussian noise through Bayesian analysis of the true dimensionality of the data, i.e., the number of activation and non-Gaussian noise sources. This enables us to carry out probabilistic modeling and achieves an asymptotically unique decomposition of the data. It reduces problems of interpretation, as each final independent component is now much more likely to be due to only one physical or physiological process. We also describe other improvements to standard ICA, such as temporal prewhitening and variance normalization of timeseries, the latter being particularly useful in the context of dimensionality reduction when weak activation is present. We discuss the use of prior information about the spatiotemporal nature of the source processes, and an alternative-hypothesis testing approach for inference, using Gaussian mixture models. The performance of our approach is illustrated and evaluated on real and artificial FMRI data, and compared to the spatio-temporal accuracy of results obtained from classical ICA and GLM analyses.

Algorithms↗

PubMed2005

Bayesian predictions of final outcomes: regulatory approval of a spinal implant.

We describe a randomized controlled trial of an investigational spinal implant. The investigational device has an obvious benefit in comparison with control in that it precludes the need for harvesting bone graft and the pain and morbidity associated with it. Therefore, the principal comparison is one of noninferiority. The primary endpoint is overall success at two years. The "noninferiority margin" is 10%. Waiting for two years after the last patient's surgery may not be necessary depending on earlier measurements of success. We model the relationship between one- and two-year results. Our Bayesian analysis considers all available information, including some patients who have both one- and two-year results and some patients who have only one-year results. Our study provides an example in which Bayesian predictive modeling provided earlier information than otherwise and therefore it shortened the time line of the development of a therapeutic strategy.

Bayes Theorem↗

PubMed2025

Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

OBJECTIVE: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype genome-wide association study (GWAS) meta-analysis. METHODS: We performed cross-phenotype GWAS meta-analysis and Bayesian colocalization analysis for patients with SSc and patients with PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, Bayesian colocalization analyses with expression quantitative trait loci and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies. Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. RESULTS: We detected a strong genetic correlation between SSc and PBC (global genetic correlation = 0.84, P = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 nonhuman leukocyte antigens loci that reached genome-wide significance (P < 5 × 10-8). Evidence of shared causal variants between patients with SSc and patients with PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. CONCLUSION: Our study supports a strong shared genetic susceptibility between SSc and PBC. Using cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Humans↗

PubMed1996

A discrete firing event analysis of the adaptive cluster expansion network.

This paper describes how a hierarchical network for encoding sensor data (the adaptive cluster expansion network) can be constructed by linking together a number of elementary modules, each of which is a simple two-layer encoder/decoder network. To achieve this goal, a Bayesian analysis is applied to the discrete neural firing events that occur within each layer of the network.

Journal Article↗

PubMed2004

Contribution of RPB2 to multilocus phylogenetic studies of the euascomycetes (Pezizomycotina, Fungi) with special emphasis on the lichen-forming Acarosporaceae and evolution of polyspory.

Despite the recent progress in molecular phylogenetics, many of the deepest relationships among the main lineages of the largest fungal phylum, Ascomycota, remain unresolved. To increase both resolution and support on a large-scale phylogeny of lichenized and non-lichenized ascomycetes, we combined the protein coding-gene RPB2 with the traditionally used nuclear ribosomal genes SSU and LSU. Our analyses resulted in the naming of the new subclasses Acarosporomycetidae and Ostropomycetidae, and the new class Lichinomycetes, as well as the establishment of the phylogenetic placement and novel circumscription of the lichen-forming fungi family Acarosporaceae. The delimitation of this family has been problematic over the past century, because its main diagnostic feature, true polyspory (numerous spores issued from multiple post-meiosis mitoses) with over 100 spores per ascus, is probably not restricted to the Acarosporaceae. This observation was confirmed by our reconstruction of the origin and evolution of this form of true polyspory using maximum likelihood as the optimality criterion. The various phylogenetic analyses carried out on our data sets allowed us to conclude that: (1) the inclusion of phylogenetic signal from ambiguously aligned regions into the maximum parsimony analyses proved advantageous in reconstructing phylogeny; however, when more data become available, Bayesian analysis using different models of evolution is likely to be more efficient; (2) neighbor-joining bootstrap proportions seem to be more appropriate in detecting topological conflict between data partitions of large-scale phylogenies than posterior probabilities; and (3) Bayesian bootstrap proportion provides a compromise between posterior probability outcomes (i.e., higher accuracy, but with a higher number of significantly supported wrong internodes) vs. maximum likelihood bootstrap proportion outcomes (i.e., lower accuracy, with a lower number of significantly supported wrong internodes).

Ascomycota↗

PubMed1998

Heritability estimates from human twin data by incorporating historical prior information.

Bayesian methods are commonly used in some analyses of human genetic data, such as segregation and linkage analyses, but they are not typically used for analyses of human twin data. In this paper we develop a scheme for a Bayesian analysis of human twin data. We develop prior elicitation schemes to incorporate historical information. We consider three prior schemes: fully informative, semi-informative and noninformative. We use Markov chain Monte Carlo sampling algorithms to facilitate Bayesian computation and provide detailed implementation schemes. We also develop model diagnostics for assessing the goodness of fit of twin models. Using a simulation study, we show that if the purpose of the study is to estimate the intraclass correlations or heritability in twin studies, then the semi-informative prior is as informative as the fully informative prior. Finally, a real data example is used to illustrate the proposed methodologies.

Bayes Theorem↗

PubMed2001

Prospective application of Bayesian monitoring and analysis in an "open" randomized clinical trial.

We describe the prospective application of Bayesian monitoring and analysis in an ongoing large multi-centre, randomized trial in which interim results are released to investigators. Substantial variability in prior opinion led us to reject the use of elicited clinical priors for monitoring, in favour of archetypal prior distributions representing reasonable scepticism and enthusiasm. Likelihoods for odds ratios for different covariate values are derived from a logistic regression model, which allows us to incorporate information from prognostic factors without resorting to specialized software. Priors, likelihoods and posterior distributions are regularly reported to both an independent Data Monitoring Committee and the trial investigators.

Bayes Theorem↗

PubMed1994

Assessing the significance of chromosome-loss data: where are suppressor genes for bladder cancer?

Cytogenetic analysis reveals alterations of chromosome structure (losses, gains, and rearrangements of genetic material) in bladder cancer cells generated using an in vitro/in vivo transformation system. To predict possible locations of bladder cancer suppressor genes, we performed a robust Bayesian analysis of the chromosome-loss data. We postulated a simple stochastic model to describe chromosome loss during tumour progression. Posterior computations are enabled by a dynamic simulation algorithm. Ordered by decreasing posterior probability of putatively harbouring a suppressor gene, we observe significant losses on chromosomes 3, 18, 13, 10, 11, and y.

Algorithms↗

PubMed1981

Radioimmunoassay and heat denaturation enzyme assay for the detection of Tay-sachs heterozygotes during pregnancy.

Tay-Sachs disease results from a loss of activity of hexosaminidase A (HEXA) in body tissues and fluids. Heterozygotes for the disease are usually identified by their relatively low ratio of heat-labile HEX A to total hexosaminidase. During pregnancy an intermediate isoenzyme (HEX I) increases in activity in serum and obscures the heterozygote status. HEX I dose not increase in leucocytes, tears and other body tissues but because of technical difficulties in these assays we examined the feasibility of using a radioimmunoassay for HEX A. By univariate analysis, the heat denaturation assay gave a lower cost of misclassification for non-pregnant normals while RIA did so for pregnant normals. A combination of both tests led to reduced cost of misclassification compared to either alone. Bayesian analysis of bivariate gaussian density functions for heat denaturation and for radioimmunoassay of HEX isoenzymes was employed to calculate misclassification frequencies. Among the parameters examined, HEX A measured by RIA and % HEX A by heat-denaturation assay were the two having the best discriminatory power.

Acetylglucosaminidase↗

PubMed2004

Phylogenetic hypotheses for the turtle family Geoemydidae.

The turtle family Geoemydidae represents the largest, most diverse, and most poorly understood family of turtles. Little is known about this group, including intrafamilial systematics. The only complete phylogenetic hypothesis for this family positions geoemydids as paraphyletic with respect to tortoises, but this arrangement has not been accepted by many workers. We compiled a 79-taxon mitochondrial and nuclear DNA data set to reconstruct phylogenetic relationships for 65 species and subspecies representing all 23 genera of the Geoemydidae. Maximum parsimony (MP) and maximum-likelihood (ML) analyses and Bayesian analysis produced similar, well-resolved trees. Our analyses identified three main clades comprising the tortoises (Testudinidae), the old-world Geoemydidae, and the South American geoemydid genus Rhinoclemmys. Within Geoemydidae, many nodes were strongly supported, particularly based on Bayesian posterior probabilities of the combined three-gene dataset. We found that adding data for a subset of taxa improved resolution of some deeper nodes in the tree. Several strongly supported groupings within the Geoemydidae demonstrate non-monophyly of some genera and possible interspecific hybrids, and we recommend several taxonomic revisions based on available evidence.

Animals↗

PubMed2001

Implications of empirical Bayes meta-analysis for test validation.

Empirical Bayes meta-analysis provides a useful framework for examining test validation. The fixed-effects case in which rho has a single value corresponds to the inference that the situational specificity hypothesis can be rejected in a validity generalization study. A Bayesian analysis of such a case provides a simple and powerful test of rho = 0; such a test has practical implications for significance testing in test validation. The random-effects case in which sigma2rho > 0 provides an explicit method with which to assess the relative importance of local validity studies and previous meta-analyses. Simulated data are used to illustrate both cases. Results of published meta-analyses are used to show that local validation becomes increasingly important as sigma2rho increases. The meaning of the term validity generalization is explored, and the problem of what can be inferred about test transportability in the random-effects case is described.

Bayes Theorem↗

PubMedDate not supplied

Comparing methods for calculating confidence intervals for vaccine efficacy.

A method is introduced for computing a Bayesian 95 per cent posterior probability region for vaccine efficacy. This method assumes independent vague gamma prior distributions for the incidence rates on each arm of the trial, and a Poisson likelihood for the counts of incident cases of infection. The approach is similar in spirit to the Bayesian analysis of the binomial risk ratio described by Aitchison and Bacon-Shone. However, the focus of our interest is not on incorporating prior information into the design of trials for efficacy, but rather on evaluating whether or not the Bayesian approach with vague prior information produces comparable results to a frequentist approach. A review of methods for constructing exact and large sample intervals for vaccine efficacy is provided as a framework for comparison. The confidence interval methods are assessed by comparing the size and power of tests of vaccine efficacy in proposed intermediate sized randomized double blinded placebo controlled trials.

AIDS Vaccines↗

PubMed2005

Bayesian methods for early detection of changes in childhood cancer incidence: trends for acute lymphoblastic leukaemia are consistent with an infectious aetiology.

Published data on time trends in the incidence of childhood leukaemia show inconsistent patterns, with some studies showing increases and others showing relatively stable incidence rates. Data on time trends in childhood cancer incidence from the Childhood Cancer Registry of Piedmont, Italy were analysed using two different approaches: standard Poisson regression and a Bayesian regression approach including an autoregressive component. Our focus was on acute lymphoblastic leukaemia (ALL), since this is hypothesised to have an infectious aetiology, but for purposes of comparison we also conducted similar analyses for selected other childhood cancer sites (acute non-lymphoblastic leukaemia (AnLL), central nervous system (CNS) tumours and neuroblastoma (NB)). The two models fitted the data equally well, but led to different interpretations of the time trends. The first produced ever-increasing rates, while the latter produced non-monotonic patterns, particularly for ALL, which showed evidence of a cyclical pattern. The Bayesian analysis produced findings that are consistent with the hypothesis of an infectious aetiology for ALL, but not for AnLL or for solid tumours (CNS and NB). Although sudden changes in time trends should be interpreted with caution, the results of the Bayesian approach are consistent with current knowledge of the natural history of childhood ALL, including a short latency time and the postulated infectious aetiology of the disease.

Adolescent↗

PubMed2004

Mapping genes for resistance to Verticillium albo-atrum in tetraploid and diploid potato populations using haplotype association tests and genetic linkage analysis.

Verticillium wilt disease of potato is caused predominantly by Verticillium albo-atrum and V. dahliae. StVe1 -a putative QTL for resistance against V. dahliae -was previously mapped to potato chromosome 9. To develop allele-specific, SNP-based markers within the locus, the StVe1 fragment from a set of 30 North American potato cultivars was analyzed. Three distinct and highly diverse haplotypes can be distinguished at the StVe1 locus. These were detected in 97%, 33%, and 10% of the cultivars analyzed. We tested for haplotype association and for genetic linkage between the StVe1 haplotypes and resistance of tetraploid potato to V. albo-atrum. Moreover, field resistance was assessed in diploid populations with known molecular linkage maps in order to identify novel QTLs. Resistance QTLs against V. albo-atrum were detected on four chromosomes (2, 6, 9, and 12) at the diploid level, with one QTL on chromosome 2 contributing over 40% to the total phenotypic variation of the trait. At the tetraploid level, a significant association between the StVe1-839-C haplotype and susceptibility to the disease was detected, suggesting that resistance-related genes directed against V. albo-atrum and V. dahliae are located in the same genomic region of chromosome 9. However, on the basis of the present analysis, we cannot determine whether these genes are closely linked or if a single gene provides resistance against both Verticillium species. To assess the usefulness of the StVe1-839-C haplotype for marker-assisted selection, we subjected the resistance data to Bayesian analysis, and calculated positive (0.65) and negative (0.75) predictive values, and overall predictive accuracy (0.72). Our results indicate that tagging of additional genes for resistance to Verticillium with molecular markers will be required for efficient marker-assisted selection.

Base Sequence↗

PubMed2003

Phylogenetic relationships of Peronospora and related genera based on nuclear ribosomal ITS sequences.

In order to investigate phylogenetic relationships of selected members of Peronosporaceae to the genera Pythium, Halophkytophthora, Phytophthora, and Peronophythora, Bayesian analysis of partial sequences of the ITS1-5.8S-ITS2 region was performed. In addition, sequences of the complete ITS1-5.8S-ITS2 region were analysed for 101 collections belonging to the genera Peronospora, Hyaloperonospora, Perofascia, Pseudoperonospora, Phytophthora and Peronophythora, using Bayesian inference of phylogeny and maximum parsimony. The results confirm a close relationship of these genera. The strongly supported Peronosporaceae clade is located within the paraphyletic genus Phytophthora (including Peronophythora). Monophyly of the genera Pseudoperonospora and Hyaloperonospora are strongly supported, but monophyly of Peronospora s. str. can neither be confirmed nor rejected. Within Peronospora s. str., basic relationships often remain unclear; however, some groups form highly supported monophyletic clades. Peronospora species parasitising the same host families or orders are only partly resolved as monophyletic, indicating frequent host-jumping also between distantly related host families. All species inhabiting flowers of different host families form a strongly supported monophyletic group.

Base Sequence↗

PubMed1989

A quality assurance model of operative mortality in coronary artery surgery.

Quality assurance in coronary artery bypass grafting (CABG) surgery requires a comparison of operative mortality against an accepted standard of care. Raw mortality statistics are unacceptable in this context, and risk factor analysis is essential. However, this principle has not been adequately demonstrated in previous reports. Our goal in this study was to develop a risk model of accepted CABG mortality and illustrate its proper use in coronary artery surgery. The model was derived from a Bayesian analysis of 6,630 patients undergoing CABG in the Coronary Artery Surgery Study (CASS) registry. Age, sex, ventricular function, previous myocardial infarction, extent of coronary artery disease, unstable angina, and surgical priority were used by the model to sort patients into risk categories. From January 1984 through December 1987, 840 patients underwent isolated CABG at our hospital. With raw mortality data, the 3.9% (33/840) mortality of our patients was significantly different from the 2.3% (153/6,630) CASS mortality (p less than 0.001). When our patients were entered into the CASS model for risk stratification, however, our CABG mortality conformed to the CASS experience. These results illustrate the fallacy of using raw mortality statistics for interinstitutional comparisons. This type of risk model is a fundamental element of CABG quality assurance.

Aged↗

PubMed1997

Radiological evaluation of lymph node metastases in patients with cervical cancer. A meta-analysis.

OBJECTIVE: To apply meta-analysis to compare the utility of lymphangiography (LAG), computed tomography (CT), and magnetic resonance (MR) imaging for the diagnosis of lymph node metastasis in patients with cervical cancer. DATA SOURCES: MEDLINE literature search and manual reviews of article bibliographies. STUDY SELECTION: Studies selected included at least 20 patients with imaging-histologic correlation, described diagnostic criteria for lymph node metastasis, and presented data to allow calculation of contingency tables. DATA EXTRACTION: Independently by 2 investigators, stratified for stage of disease (early vs late) and for lymph node location (pelvic vs para-aortic). DATA SYNTHESIS: Seventeen studies met the inclusion criteria for LAG, 17 for CT, and 10 for MR imaging. Summary receiver operator characteristic analysis showed no significant differences in the overall performance of LAG, CT, and MR imaging. There was, however, a trend toward better performance for MR imaging than for LAG or CT, both globally and when stratified for stage of disease or for lymph node location. Bayesian analysis of clinical utility showed only moderate increases in positive posttest probability of lymph node metastasis for all methods. Negative test results had a greater impact and, depending on the clinical setting, decreased the probability of lymph node metastasis from 15% to 44% (pretest) to 3% to 18% (posttest). CONCLUSIONS: The LAG, CT, and MR imaging perform similarly in the detection of lymph node metastasis from cervical cancer. As CT and MR imaging are less invasive than LAG and also assess local tumor extent, they should be considered the preferred adjuncts to clinical evaluation of invasive cervical cancer.

Female↗