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Sample records for genome bayesian scan

  1. Genome Scans for Detecting Footprints of Local Adaptation Using a Bayesian Factor Model

    Science.gov (United States)

    Duforet-Frebourg, Nicolas; Bazin, Eric; Blum, Michael G.B.

    2014-01-01

    There is a considerable impetus in population genomics to pinpoint loci involved in local adaptation. A powerful approach to find genomic regions subject to local adaptation is to genotype numerous molecular markers and look for outlier loci. One of the most common approaches for selection scans is based on statistics that measure population differentiation such as FST. However, there are important caveats with approaches related to FST because they require grouping individuals into populations and they additionally assume a particular model of population structure. Here, we implement a more flexible individual-based approach based on Bayesian factor models. Factor models capture population structure with latent variables called factors, which can describe clustering of individuals into populations or isolation-by-distance patterns. Using hierarchical Bayesian modeling, we both infer population structure and identify outlier loci that are candidates for local adaptation. In order to identify outlier loci, the hierarchical factor model searches for loci that are atypically related to population structure as measured by the latent factors. In a model of population divergence, we show that it can achieve a 2-fold or more reduction of false discovery rate compared with the software BayeScan or with an FST approach. We show that our software can handle large data sets by analyzing the single nucleotide polymorphisms of the Human Genome Diversity Project. The Bayesian factor model is implemented in the open-source PCAdapt software. PMID:24899666

  2. Integrative bayesian network analysis of genomic data.

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    Ni, Yang; Stingo, Francesco C; Baladandayuthapani, Veerabhadran

    2014-01-01

    Rapid development of genome-wide profiling technologies has made it possible to conduct integrative analysis on genomic data from multiple platforms. In this study, we develop a novel integrative Bayesian network approach to investigate the relationships between genetic and epigenetic alterations as well as how these mutations affect a patient's clinical outcome. We take a Bayesian network approach that admits a convenient decomposition of the joint distribution into local distributions. Exploiting the prior biological knowledge about regulatory mechanisms, we model each local distribution as linear regressions. This allows us to analyze multi-platform genome-wide data in a computationally efficient manner. We illustrate the performance of our approach through simulation studies. Our methods are motivated by and applied to a multi-platform glioblastoma dataset, from which we reveal several biologically relevant relationships that have been validated in the literature as well as new genes that could potentially be novel biomarkers for cancer progression.

  3. A mixture copula Bayesian network model for multimodal genomic data

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    Qingyang Zhang

    2017-04-01

    Full Text Available Gaussian Bayesian networks have become a widely used framework to estimate directed associations between joint Gaussian variables, where the network structure encodes the decomposition of multivariate normal density into local terms. However, the resulting estimates can be inaccurate when the normality assumption is moderately or severely violated, making it unsuitable for dealing with recent genomic data such as the Cancer Genome Atlas data. In the present paper, we propose a mixture copula Bayesian network model which provides great flexibility in modeling non-Gaussian and multimodal data for causal inference. The parameters in mixture copula functions can be efficiently estimated by a routine expectation–maximization algorithm. A heuristic search algorithm based on Bayesian information criterion is developed to estimate the network structure, and prediction can be further improved by the best-scoring network out of multiple predictions from random initial values. Our method outperforms Gaussian Bayesian networks and regular copula Bayesian networks in terms of modeling flexibility and prediction accuracy, as demonstrated using a cell signaling data set. We apply the proposed methods to the Cancer Genome Atlas data to study the genetic and epigenetic pathways that underlie serous ovarian cancer.

  4. Bayesian genomic selection: the effect of haplotype lenghts and priors

    DEFF Research Database (Denmark)

    Villumsen, Trine Michelle; Janss, Luc

    2009-01-01

    Breeding values for animals with marker data are estimated using a genomic selection approach where data is analyzed using Bayesian multi-marker association models. Fourteen model scenarios with varying haplotype lengths, hyper parameter and prior distributions were compared to find the scenario ...

  5. A genome-wide scan for preeclampsia in the Netherlands

    NARCIS (Netherlands)

    Lachmeijer, AMA; Arngrimsson, R; Bastiaans, EJ; Frigge, ML; Pals, G; Sigurdardottir, S; Stefansson, H; Palsson, B; Nicolae, D; Kong, A; Aarnoudse, JG; Gulcher, [No Value; Dekker, GA; ten Kate, LP; Stefansson, K

    2001-01-01

    Preeclampsia, hallmarked by de novo hypertension and proteinuria in pregnancy, has a familial tendency. Recently, a large Icelandic genome-wide scan provided evidence for a maternal susceptibility locus for preeclampsia on chromosome 2p13 which was confirmed by a genome scan from Australia and New

  6. VIGoR: Variational Bayesian Inference for Genome-Wide Regression

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    Akio Onogi

    2016-04-01

    Full Text Available Genome-wide regression using a number of genome-wide markers as predictors is now widely used for genome-wide association mapping and genomic prediction. We developed novel software for genome-wide regression which we named VIGoR (variational Bayesian inference for genome-wide regression. Variational Bayesian inference is computationally much faster than widely used Markov chain Monte Carlo algorithms. VIGoR implements seven regression methods, and is provided as a command line program package for Linux/Mac, and as a cross-platform R package. In addition to model fitting, cross-validation and hyperparameter tuning using cross-validation can be automatically performed by modifying a single argument. VIGoR is available at https://github.com/Onogi/VIGoR. The R package is also available at https://cran.r-project.org/web/packages/VIGoR/index.html.

  7. Bayesian Hierarchical Model for Estimating Gene Expression Intensity Using Multiple Scanned Microarrays

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    Auvinen Petri

    2008-01-01

    Full Text Available We propose a method for improving the quality of signal from DNA microarrays by using several scans at varying scanner sen-sitivities. A Bayesian latent intensity model is introduced for the analysis of such data. The method improves the accuracy at which expressions can be measured in all ranges and extends the dynamic range of measured gene expression at the high end. Our method is generic and can be applied to data from any organism, for imaging with any scanner that allows varying the laser power, and for extraction with any image analysis software. Results from a self-self hybridization data set illustrate an improved precision in the estimation of the expression of genes compared to what can be achieved by applying standard methods and using only a single scan.

  8. Suspected pulmonary embolism and lung scan interpretation: trial of a Bayesian reporting method.

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    Becker, D M; Philbrick, J T; Schoonover, F W; Teates, C D

    1990-01-01

    To determine whether a Bayesian method of lung scan (LS) reporting could influence the management of patients with suspected pulmonary embolism (PE). 1) A descriptive study of the diagnostic process for suspected PE using the new reporting method; 2) a non-experimental evaluation of the reporting method comparing prospective patients and historical controls; and 3) a survey of physicians' reactions to the reporting innovation. University of Virginia Hospital. Of 148 consecutive patients enrolled at the time of LS, 129 were completely evaluated; 75 patients scanned the previous year served as controls. The LS results of patients with suspected PE were reported as posttest probabilities of PE calculated from physician-provided pretest probabilities and the likelihood ratios for PE of LS interpretations. Despite the Bayesian intervention, the confirmation or exclusion of PE was often based on inconclusive evidence. PE was considered by the clinician to be ruled out in 98% of patients with posttest probabilities less than 25% and ruled in for 95% of patients with posttest probabilities greater than 75%. Prospective patients and historical controls were similar in terms of tests ordered after the LS (e.g., pulmonary angiography). Patients with intermediate or indeterminate lung scan results had the highest proportion of subsequent testing. Most physicians (80%) found the reporting innovation to be helpful, either because it confirmed clinical judgement (94 cases) or because it led to additional testing (7 cases). Despite the probabilistic guidance provided by the study, the diagnosis of PE was often neither clearly established nor excluded. While physicians appreciated the innovation and were not confused by the terminology, their clinical decision making was not clearly enhanced.

  9. Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.

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    Ildikó Ungvári

    Full Text Available Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls. The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA. This method uses bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated.With frequentist methods one SNP (rs3751464 in the FRMD6 gene provided evidence for an association with asthma (OR = 1.43(1.2-1.8; p = 3×10(-4. The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics.In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

  10. Bayesian Deconvolution for Angular Super-Resolution in Forward-Looking Scanning Radar

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    Yuebo Zha

    2015-03-01

    Full Text Available Scanning radar is of notable importance for ground surveillance, terrain mapping and disaster rescue. However, the angular resolution of a scanning radar image is poor compared to the achievable range resolution. This paper presents a deconvolution algorithm for angular super-resolution in scanning radar based on Bayesian theory, which states that the angular super-resolution can be realized by solving the corresponding deconvolution problem with the maximum a posteriori (MAP criterion. The algorithm considers that the noise is composed of two mutually independent parts, i.e., a Gaussian signal-independent component and a Poisson signal-dependent component. In addition, the Laplace distribution is used to represent the prior information about the targets under the assumption that the radar image of interest can be represented by the dominant scatters in the scene. Experimental results demonstrate that the proposed deconvolution algorithm has higher precision for angular super-resolution compared with the conventional algorithms, such as the Tikhonov regularization algorithm, the Wiener filter and the Richardson–Lucy algorithm.

  11. Bayesian deconvolution for angular super-resolution in forward-looking scanning radar.

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    Zha, Yuebo; Huang, Yulin; Sun, Zhichao; Wang, Yue; Yang, Jianyu

    2015-03-23

    Scanning radar is of notable importance for ground surveillance, terrain mapping and disaster rescue. However, the angular resolution of a scanning radar image is poor compared to the achievable range resolution. This paper presents a deconvolution algorithm for angular super-resolution in scanning radar based on Bayesian theory, which states that the angular super-resolution can be realized by solving the corresponding deconvolution problem with the maximum a posteriori (MAP) criterion. The algorithm considers that the noise is composed of two mutually independent parts, i.e., a Gaussian signal-independent component and a Poisson signal-dependent component. In addition, the Laplace distribution is used to represent the prior information about the targets under the assumption that the radar image of interest can be represented by the dominant scatters in the scene. Experimental results demonstrate that the proposed deconvolution algorithm has higher precision for angular super-resolution compared with the conventional algorithms, such as the Tikhonov regularization algorithm, the Wiener filter and the Richardson-Lucy algorithm.

  12. Genome-Wide Scan Reveals Mutation Associated with Melanoma

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    ... Q R S T U V W X Y Z We want to hear from you You are here: News & Events 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 Spotlight on Research 2012 July 2012 (historical) Genome-Wide Scan Reveals Mutation Associated with Melanoma A team of ...

  13. Asthma and atopy - a total genome scan for susceptibility genes

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schiøtz, P O;

    2002-01-01

    atopy, allergic asthma and increased total IgE. We performed a total genome scan using 446 microsatellite markers and obtained nonparametric linkage results from the MAPMAKER/SIBS computer program. RESULTS: Our study revealed four candidate regions (MLS > 2) on chromosome 1p36, 3q21-q22, 5q31 and 6p24-p...

  14. Integration of association statistics over genomic regions using Bayesian adaptive regression splines

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    Zhang Xiaohua

    2003-11-01

    Full Text Available Abstract In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS. For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.

  15. AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

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    Mei Lingling

    2011-11-01

    Full Text Available Abstract Background To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance. Results Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA. Conclusions AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and

  16. Bayesian inference of genetic parameters for ultrasound scanning traits of Kivircik lambs.

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    Cemal, I; Karaman, E; Firat, M Z; Yilmaz, O; Ata, N; Karaca, O

    2017-03-01

    Ultrasound scanning traits have been adapted in selection programs in many countries to improve carcass traits for lean meat production. As the genetic parameters of the traits interested are important for breeding programs, the estimation of these parameters was aimed at the present investigation. The estimated parameters were direct and maternal heritability as well as genetic correlations between the studied traits. The traits were backfat thickness (BFT), skin+backfat thickness (SBFT), eye muscle depth (MD) and live weights at the day of scanning (LW). The breed investigated was Kivircik, which has a high quality of meat. Six different multi-trait animal models were fitted to determine the most suitable model for the data using Bayesian approach. Based on deviance information criterion, a model that includes direct additive genetic effects, maternal additive genetic effects, direct maternal genetic covariance and maternal permanent environmental effects revealed to be the most appropriate for the data, and therefore, inferences were built on the results of that model. The direct heritability estimates for BFT, SBFT, MD and LW were 0.26, 0.26, 0.23 and 0.09, whereas the maternal heritability estimates were 0.27, 0.27, 0.24 and 0.20, respectively. Negative genetic correlations were obtained between direct and maternal effects for BFT, SBFT and MD. Both direct and maternal genetic correlations between traits were favorable, whereas BFT-MD and SBFT-MD had negligible direct genetic correlation. The highest direct and maternal genetic correlations were between BFT and SBFT (0.39) and between MD and LW (0.48), respectively. Our results, in general, indicated that maternal effects should be accounted for in estimation of genetic parameters of ultrasound scanning traits in Kivircik lambs, and SBFT can be used as a selection criterion to improve BFT.

  17. Genomic prediction and genomic variance partitioning of daily and residual feed intake in pigs using Bayesian Power Lasso models

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Janss, Luc L G; Strathe, Anders B

    Improvement of feed efficiency is essential in pig breeding and selection for reduced residual feed intake (RFI) is an option. The study applied Bayesian Power LASSO (BPL) models with different power parameter to investigate genetic architecture, to predict genomic breeding values, and to partition...... genomic variance for RFI and daily feed intake (DFI). A total of 1272 Duroc pigs had both genotypic and phenotypic records for these traits. Significant SNPs were detected on chromosome 1 (SSC 1) and SSC 14 for RFI and on SSC 1 for DFI. BPL had similar accuracy and bias as GBLUP but power parameters had...

  18. Genomic prediction and genomic variance partitioning of daily and residual feed intake in pigs using Bayesian Power Lasso models

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Janss, L. L. G.; Strathe, Anders Bjerring

    Improvement of feed efficiency is essential in pig breeding and selection for reduced residual feed intake (RFI) is an option. The study applied Bayesian Power LASSO (BPL) models with different power parameter to investigate genetic architecture, to predict genomic breeding values, and to partition...... genomic variance for RFI and daily feed intake (DFI). A total of 1272 Duroc pigs had both genotypic and phenotypic records for these traits. Significant SNPs were detected on chromosome 1 (SSC 1) and SSC 14 for RFI and on SSC 1 for DFI. BPL models had similar accuracy and bias as GBLUP method but use...

  19. Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates.

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    Gautier, Mathieu

    2015-12-01

    In population genomics studies, accounting for the neutral covariance structure across population allele frequencies is critical to improve the robustness of genome-wide scan approaches. Elaborating on the BayEnv model, this study investigates several modeling extensions (i) to improve the estimation accuracy of the population covariance matrix and all the related measures, (ii) to identify significantly overly differentiated SNPs based on a calibration procedure of the XtX statistics, and (iii) to consider alternative covariate models for analyses of association with population-specific covariables. In particular, the auxiliary variable model allows one to deal with multiple testing issues and, providing the relative marker positions are available, to capture some linkage disequilibrium information. A comprehensive simulation study was carried out to evaluate the performances of these different models. Also, when compared in terms of power, robustness, and computational efficiency to five other state-of-the-art genome-scan methods (BayEnv2, BayScEnv, BayScan, flk, and lfmm), the proposed approaches proved highly effective. For illustration purposes, genotyping data on 18 French cattle breeds were analyzed, leading to the identification of 13 strong signatures of selection. Among these, four (surrounding the KITLG, KIT, EDN3, and ALB genes) contained SNPs strongly associated with the piebald coloration pattern while a fifth (surrounding PLAG1) could be associated to morphological differences across the populations. Finally, analysis of Pool-Seq data from 12 populations of Littorina saxatilis living in two different ecotypes illustrates how the proposed framework might help in addressing relevant ecological issues in nonmodel species. Overall, the proposed methods define a robust Bayesian framework to characterize adaptive genetic differentiation across populations. The BayPass program implementing the different models is available at http://www1.montpellier.inra.fr/CBGP/software/baypass/.

  20. Single- and Bayesian Multi-Marker Genome-Wide Association for Haematological Parameters in Pigs.

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    Siriluck Ponsuksili

    Full Text Available Haematological traits are important traits that show associations with immune and metabolic status, as well as diseases in humans and animals. Mapping genome regions that affect the blood cell traits can contribute to the identification of genomic features useable as biomarkers for immune, disease and metabolic status. A genome-wide association study (GWAS was conducted using PorcineSNP60 BeadChips. Single-marker and Bayesian multi-marker approaches were integrated to identify genomic regions and corresponding genes overlapping for both methods. GWAS was performed for haematological traits of 591 German Landrace pig. Heritability estimates for haematological traits were medium to high. In total 252 single SNPs associated with 12 haematological traits were identified (NegLog10 of p-value > 5. The Bayesian multi-marker approach revealed 102 QTL regions across the genome, indicated by 1-Mb windows with contribution to additive genetic variance above 0.5%. The integration of both methods resulted in 24 overlapping QTL regions. This study identified overlapping QTL regions from single- and multi-marker approaches for haematological traits. Identifying candidate genes that affect blood cell traits provides the first step towards the understanding of the molecular basis of haematological phenotypes.

  1. Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion.

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    Xi, Ruibin; Hadjipanayis, Angela G; Luquette, Lovelace J; Kim, Tae-Min; Lee, Eunjung; Zhang, Jianhua; Johnson, Mark D; Muzny, Donna M; Wheeler, David A; Gibbs, Richard A; Kucherlapati, Raju; Park, Peter J

    2011-11-15

    DNA copy number variations (CNVs) play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders. Array comparative genomic hybridization has been used widely to identify CNVs genome wide, but the next-generation sequencing technology provides an opportunity to characterize CNVs genome wide with unprecedented resolution. In this study, we developed an algorithm to detect CNVs from whole-genome sequencing data and applied it to a newly sequenced glioblastoma genome with a matched control. This read-depth algorithm, called BIC-seq, can accurately and efficiently identify CNVs via minimizing the Bayesian information criterion. Using BIC-seq, we identified hundreds of CNVs as small as 40 bp in the cancer genome sequenced at 10× coverage, whereas we could only detect large CNVs (> 15 kb) in the array comparative genomic hybridization profiles for the same genome. Eighty percent (14/16) of the small variants tested (110 bp to 14 kb) were experimentally validated by quantitative PCR, demonstrating high sensitivity and true positive rate of the algorithm. We also extended the algorithm to detect recurrent CNVs in multiple samples as well as deriving error bars for breakpoints using a Gibbs sampling approach. We propose this statistical approach as a principled yet practical and efficient method to estimate CNVs in whole-genome sequencing data.

  2. Genome-wide scans detect adaptation to aridity in a widespread forest tree species.

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    Steane, Dorothy A; Potts, Brad M; McLean, Elizabeth; Prober, Suzanne M; Stock, William D; Vaillancourt, René E; Byrne, Margaret

    2014-05-01

    Patterns of adaptive variation within plant species are best studied through common garden experiments, but these are costly and time-consuming, especially for trees that have long generation times. We explored whether genome-wide scanning technology combined with outlier marker detection could be used to detect adaptation to climate and provide an alternative to common garden experiments. As a case study, we sampled nine provenances of the widespread forest tree species, Eucalyptus tricarpa, across an aridity gradient in southeastern Australia. Using a Bayesian analysis, we identified a suite of 94 putatively adaptive (outlying) sequence-tagged markers across the genome. Population-level allele frequencies of these outlier markers were strongly correlated with temperature and moisture availability at the site of origin, and with population differences in functional traits measured in two common gardens. Using the output from a canonical analysis of principal coordinates, we devised a metric that provides a holistic measure of genomic adaptation to aridity that could be used to guide assisted migration or genetic augmentation. © 2014 John Wiley & Sons Ltd.

  3. Asthma and atopy - a total genome scan for susceptibility genes

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schiøtz, P O

    2002-01-01

    . Investigation of different populations will further clarify the topic. We therefore evaluated allergic asthma and increased total and specific IgE in 39, 45 and 57 sib-pairs from 100 Danish allergy families. METHODS: Affected sib-pairs meeting a narrow phenotype definition were selected for the three phenotypes...... atopy, allergic asthma and increased total IgE. We performed a total genome scan using 446 microsatellite markers and obtained nonparametric linkage results from the MAPMAKER/SIBS computer program. RESULTS: Our study revealed four candidate regions (MLS > 2) on chromosome 1p36, 3q21-q22, 5q31 and 6p24-p...

  4. Inferring genetic architecture of complex traits using Bayesian integrative analysis of genome and transcriptiome data

    DEFF Research Database (Denmark)

    Ehsani, Alireza; Sørensen, Peter; Pomp, Daniel;

    2012-01-01

    Background To understand the genetic architecture of complex traits and bridge the genotype-phenotype gap, it is useful to study intermediate -omics data, e.g. the transcriptome. The present study introduces a method for simultaneous quantification of the contributions from single nucleotide...... polymorphisms (SNPs) and transcript abundances in explaining phenotypic variance, using Bayesian whole-omics models. Bayesian mixed models and variable selection models were used and, based on parameter samples from the model posterior distributions, explained variances were further partitioned at the level......-modal distribution of genomic values collapses, when gene expressions are added to the model Conclusions With increased availability of various -omics data, integrative approaches are promising tools for understanding the genetic architecture of complex traits. Partitioning of explained variances at the chromosome...

  5. A new approach for using genome scans to detect recent positive selection in the human genome.

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    Kun Tang

    2007-07-01

    Full Text Available Genome-wide scanning for signals of recent positive selection is essential for a comprehensive and systematic understanding of human adaptation. Here, we present a genomic survey of recent local selective sweeps, especially aimed at those nearly or recently completed. A novel approach was developed for such signals, based on contrasting the extended haplotype homozygosity (EHH profiles between populations. We applied this method to the genome single nucleotide polymorphism (SNP data of both the International HapMap Project and Perlegen Sciences, and detected widespread signals of recent local selection across the genome, consisting of both complete and partial sweeps. A challenging problem of genomic scans of recent positive selection is to clearly distinguish selection from neutral effects, given the high sensitivity of the test statistics to departures from neutral demographic assumptions and the lack of a single, accurate neutral model of human history. We therefore developed a new procedure that is robust across a wide range of demographic and ascertainment models, one that indicates that certain portions of the genome clearly depart from neutrality. Simulations of positive selection showed that our tests have high power towards strong selection sweeps that have undergone fixation. Gene ontology analysis of the candidate regions revealed several new functional groups that might help explain some important interpopulation differences in phenotypic traits.

  6. Genome scan for meat quality traits in Nelore beef cattle.

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    Tizioto, P C; Decker, J E; Taylor, J F; Schnabel, R D; Mudadu, M A; Silva, F L; Mourão, G B; Coutinho, L L; Tholon, P; Sonstegard, T S; Rosa, A N; Alencar, M M; Tullio, R R; Medeiros, S R; Nassu, R T; Feijó, G L D; Silva, L O C; Torres, R A; Siqueira, F; Higa, R H; Regitano, L C A

    2013-11-01

    Meat quality traits are economically important because they affect consumers' acceptance, which, in turn, influences the demand for beef. However, selection to improve meat quality is limited by the small numbers of animals on which meat tenderness can be evaluated due to the cost of performing shear force analysis and the resultant damage to the carcass. Genome wide-association studies for Warner-Bratzler shear force measured at different times of meat aging, backfat thickness, ribeye muscle area, scanning parameters [lightness, redness (a*), and yellowness] to ascertain color characteristics of meat and fat, water-holding capacity, cooking loss (CL), and muscle pH were conducted using genotype data from the Illumina BovineHD BeadChip array to identify quantitative trait loci (QTL) in all phenotyped Nelore cattle. Phenotype count for these animals ranged from 430 to 536 across traits. Meat quality traits in Nelore are controlled by numerous QTL of small effect, except for a small number of large-effect QTL identified for a*fat, CL, and pH. Genomic regions harboring these QTL and the pathways in which the genes from these regions act appear to differ from those identified in taurine cattle for meat quality traits. These results will guide future QTL mapping studies and the development of models for the prediction of genetic merit to implement genomic selection for meat quality in Nelore cattle.

  7. Genome-Wide Scan for Methylation Profiles in Keloids

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    Lamont R. Jones

    2015-01-01

    Full Text Available Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63% were hypomethylated and 56 (37% hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation.

  8. A two step Bayesian approach for genomic prediction of breeding values

    DEFF Research Database (Denmark)

    Mahdi Shariati, Mohammad; Sørensen, Peter; Janss, Luc

    2012-01-01

    Background: In genomic models that assign an individual variance to each marker, the contribution of one marker to the posterior distribution of the marker variance is only one degree of freedom (df), which introduces many variance parameters with only little information per variance parameter...... of predicted breeding values. However, the accuracies of predicted breeding values were lower than Bayesian methods with marker specific variances. Conclusions: Grouping markers is less flexible than allowing each marker to have a specific marker variance but, by grouping, the power to estimate marker...

  9. A Genomic Bayesian Multi-trait and Multi-environment Model.

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    Montesinos-López, Osval A; Montesinos-López, Abelardo; Crossa, José; Toledo, Fernando H; Pérez-Hernández, Oscar; Eskridge, Kent M; Rutkoski, Jessica

    2016-09-08

    When information on multiple genotypes evaluated in multiple environments is recorded, a multi-environment single trait model for assessing genotype × environment interaction (G × E) is usually employed. Comprehensive models that simultaneously take into account the correlated traits and trait × genotype × environment interaction (T × G × E) are lacking. In this research, we propose a Bayesian model for analyzing multiple traits and multiple environments for whole-genome prediction (WGP) model. For this model, we used Half-[Formula: see text] priors on each standard deviation term and uniform priors on each correlation of the covariance matrix. These priors were not informative and led to posterior inferences that were insensitive to the choice of hyper-parameters. We also developed a computationally efficient Markov Chain Monte Carlo (MCMC) under the above priors, which allowed us to obtain all required full conditional distributions of the parameters leading to an exact Gibbs sampling for the posterior distribution. We used two real data sets to implement and evaluate the proposed Bayesian method and found that when the correlation between traits was high (>0.5), the proposed model (with unstructured variance-covariance) improved prediction accuracy compared to the model with diagonal and standard variance-covariance structures. The R-software package Bayesian Multi-Trait and Multi-Environment (BMTME) offers optimized C++ routines to efficiently perform the analyses. Copyright © 2016 Montesinos-López et al.

  10. Integration of Multiple Genomic Data Sources in a Bayesian Cox Model for Variable Selection and Prediction.

    Science.gov (United States)

    Treppmann, Tabea; Ickstadt, Katja; Zucknick, Manuela

    2017-01-01

    Bayesian variable selection becomes more and more important in statistical analyses, in particular when performing variable selection in high dimensions. For survival time models and in the presence of genomic data, the state of the art is still quite unexploited. One of the more recent approaches suggests a Bayesian semiparametric proportional hazards model for right censored time-to-event data. We extend this model to directly include variable selection, based on a stochastic search procedure within a Markov chain Monte Carlo sampler for inference. This equips us with an intuitive and flexible approach and provides a way for integrating additional data sources and further extensions. We make use of the possibility of implementing parallel tempering to help improve the mixing of the Markov chains. In our examples, we use this Bayesian approach to integrate copy number variation data into a gene-expression-based survival prediction model. This is achieved by formulating an informed prior based on copy number variation. We perform a simulation study to investigate the model's behavior and prediction performance in different situations before applying it to a dataset of glioblastoma patients and evaluating the biological relevance of the findings.

  11. BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes.

    Science.gov (United States)

    de Santiago, Ines; Liu, Wei; Yuan, Ke; O'Reilly, Martin; Chilamakuri, Chandra Sekhar Reddy; Ponder, Bruce A J; Meyer, Kerstin B; Markowetz, Florian

    2017-02-24

    Allele-specific measurements of transcription factor binding from ChIP-seq data are key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic diversity. However, most methods of detecting an allelic imbalance assume diploid genomes. This assumption severely limits their applicability to cancer samples with frequent DNA copy-number changes. Here we present a Bayesian statistical approach called BaalChIP to correct for the effect of background allele frequency on the observed ChIP-seq read counts. BaalChIP allows the joint analysis of multiple ChIP-seq samples across a single variant and outperforms competing approaches in simulations. Using 548 ENCODE ChIP-seq and six targeted FAIRE-seq samples, we show that BaalChIP effectively corrects allele-specific analysis for copy-number variation and increases the power to detect putative cis-acting regulatory variants in cancer genomes.

  12. Bootstrap, Bayesian probability and maximum likelihood mapping: exploring new tools for comparative genome analyses

    Directory of Open Access Journals (Sweden)

    Gogarten J Peter

    2002-02-01

    Full Text Available Abstract Background Horizontal gene transfer (HGT played an important role in shaping microbial genomes. In addition to genes under sporadic selection, HGT also affects housekeeping genes and those involved in information processing, even ribosomal RNA encoding genes. Here we describe tools that provide an assessment and graphic illustration of the mosaic nature of microbial genomes. Results We adapted the Maximum Likelihood (ML mapping to the analyses of all detected quartets of orthologous genes found in four genomes. We have automated the assembly and analyses of these quartets of orthologs given the selection of four genomes. We compared the ML-mapping approach to more rigorous Bayesian probability and Bootstrap mapping techniques. The latter two approaches appear to be more conservative than the ML-mapping approach, but qualitatively all three approaches give equivalent results. All three tools were tested on mitochondrial genomes, which presumably were inherited as a single linkage group. Conclusions In some instances of interphylum relationships we find nearly equal numbers of quartets strongly supporting the three possible topologies. In contrast, our analyses of genome quartets containing the cyanobacterium Synechocystis sp. indicate that a large part of the cyanobacterial genome is related to that of low GC Gram positives. Other groups that had been suggested as sister groups to the cyanobacteria contain many fewer genes that group with the Synechocystis orthologs. Interdomain comparisons of genome quartets containing the archaeon Halobacterium sp. revealed that Halobacterium sp. shares more genes with Bacteria that live in the same environment than with Bacteria that are more closely related based on rRNA phylogeny . Many of these genes encode proteins involved in substrate transport and metabolism and in information storage and processing. The performed analyses demonstrate that relationships among prokaryotes cannot be accurately

  13. Genome scan for linkage to Gilles de la Tourette syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Barr, C.L.; Livingston, J.; Williamson, R. [and others

    1994-09-01

    Gilles de la Tourette Syndrome (TS) is a familial, neuropsychiatric disorder characterized by chronic, intermittent motor and vocal tics. In addition to tics, affected individuals frequently display symptoms such as attention-deficit hyperactivity disorder and/or obsessive compulsive disorder. Genetic analyses of family data have suggested that susceptibility to the disorder is most likely due to a single genetic locus with a dominant mode of transmission and reduced penetrance. In the search for genetic linkage for TS, we have collected well-characterized pedigrees with multiple affected individuals on whom extensive diagnostic evaluations have been done. The first stage of our study is to scan the genome systematically using a panel of uniformly spaced (10 to 20 cM), highly polymorphic, microsatellite markers on 5 families segregating TS. To date, 290 markers have been typed and 3,660 non-overlapping cM of the genome have been excluded for possible linkage under the assumption of genetic homogeneity. Because of the possibility of locus heterogeneity overall summed exclusion is not considered tantamount to absolute exclusion of a disease locus in that region. The results from each family are carefully evaluated and a positive lod score in a single family is followed up by typing closely linked markers. Linkage to TS was examined by two-point analysis using the following genetic model: single autosomal dominant gene with gene frequency .003 and maximum penetrance of .99. An age-of-onset correction is included using a linear function increasing from age 2 years to 21 years. A small rate of phenocopies is also incorporated into the model. Only individuals with TS or CMT according to DSM III-R criteria were regarded as affected for the purposes of this summary. Additional markers are being tested to provide coverage at 5 cM intervals. Moreover, we are currently analyzing the data non-parametrically using the Affected-Pedigree-Member Method of linkage analysis.

  14. A genome scan for positive selection in thoroughbred horses.

    Directory of Open Access Journals (Sweden)

    Jingjing Gu

    Full Text Available Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1 deviations from expected heterozygosity (Ewens-Watterson test in Thoroughbred (n = 112 and (2 global differentiation among four geographically diverse horse populations (F(ST. We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01, insulin receptor signalling (5.0-fold enrichment; P<0.01 and lipid transport (2.2-fold enrichment; P<0.05 genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05 and focal adhesion pathway (1.9-fold enrichment; P<0.01 genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1, ACTA1 (actin, alpha 1, skeletal muscle, ACTN2 (actinin, alpha 2, ADHFE1 (alcohol dehydrogenase, iron containing, 1, MTFR1 (mitochondrial fission regulator 1, PDK4 (pyruvate dehydrogenase kinase, isozyme 4 and TNC (tenascin C. Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes

  15. In silico whole genome association scan for murine prepulse inhibition.

    Directory of Open Access Journals (Sweden)

    Bradley Todd Webb

    Full Text Available BACKGROUND: The complex trait of prepulse inhibition (PPI is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups. METHODOLOGY/PRINCIPAL FINDINGS: We have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed effects, and false discovery rate (FDR control. A genome-wide scan for PPI was conducted using over 17,000 single nucleotide polymorphisms (SNPs in 37 strains phenotyped. Eighty-nine SNPs were significant at a false discovery rate (FDR of 5%. After accounting for long-range linkage disequilibrium, we found 3 independent QTLs located on murine chromosomes 1 and 13. One of the PPI positives corresponds to a region of human chromosome 6p which includes DTNBP1, a gene implicated in schizophrenia. Another region includes the gene Tsn which alters PPI when knocked out. These genes also appear to have correlated expression with PPI. CONCLUSIONS/SIGNIFICANCE: These results support the usefulness of using an improved in silico mapping method to identify QTLs for complex traits such as PPI which can be then be used for to help identify loci influencing schizophrenia in humans.

  16. Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 complex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.

  17. Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 com-plex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.

  18. Genome-wide association study of swine farrowing traits. Part II: Bayesian analysis of marker data.

    Science.gov (United States)

    Schneider, J F; Rempel, L A; Snelling, W M; Wiedmann, R T; Nonneman, D J; Rohrer, G A

    2012-10-01

    Reproductive efficiency has a great impact on the economic success of pork (sus scrofa) production. Number born alive (NBA) and average piglet birth weight (ABW) contribute greatly to reproductive efficiency. To better understand the underlying genetics of birth traits, a genome-wide association study (GWAS) was undertaken. Samples of DNA were collected and tested using the Illumina PorcineSNP60 BeadChip from 1,152 first parity gilts. Traits included total number born (TNB), NBA, number born dead (NBD), number stillborn (NSB), number of mummies (MUM), total litter birth weight (LBW), and ABW. A total of 41,151 SNP were tested using a Bayesian approach. Beginning with the first 5 SNP on SSC1 and ending with the last 5 SNP on the SSCX, SNP were assigned to groups of 5 consecutive SNP by chromosome-position order and analyzed again using a Bayesian approach. From that analysis, 5-SNP groups were selected having no overlap with another 5-SNP groups and no overlap across chromosomes. These selected 5-SNP non-overlapping groups were defined as QTL. Of the available 8,814 QTL, 124 were found to be statistically significant (P ABW, 9 on SSC1, 3 on SSC2, 9 on SSC5, 5 on SSC6, 1 on SSC7, 2 on SSC8, 2 on SSC9, 3 on SSC10, 1 on SSC11, 3 on SSC12, 2 on SSC13, 8 on SSC14, 8 on SSC15, 1 on SSC17, and 8 on SSC18. Several candidate genes have been identified that overlap QTL locations among TNB, NBA, NBD, and ABW. These QTL when combined with information on genes found in the same regions should provide useful information that could be used for marker assisted selection, marker assisted management, or genomic selection applications in commercial pig populations.

  19. An automated annotation tool for genomic DNA sequences using GeneScan and BLAST

    Indian Academy of Sciences (India)

    Andrew M. Lynn; Chakresh Kumar Jain; K. Kosalai; Pranjan Barman; Nupur Thakur; Harish Batra; Alok Bhattacharya

    2001-04-01

    Genomic sequence data are often available well before the annotated sequence is published. We present a method for analysis of genomic DNA to identify coding sequences using the GeneScan algorithm and characterize these resultant sequences by BLAST. The routines are used to develop a system for automated annotation of genome DNA sequences.

  20. Capturing the Phylogeny of Holometabola with Mitochondrial Genome Data and Bayesian Site-Heterogeneous Mixture Models.

    Science.gov (United States)

    Song, Fan; Li, Hu; Jiang, Pei; Zhou, Xuguo; Liu, Jinpeng; Sun, Changhai; Vogler, Alfried P; Cai, Wanzhi

    2016-05-22

    After decades of debate, a mostly satisfactory resolution of relationships among the 11 recognized holometabolan orders of insects has been reached based on nuclear genes, resolving one of the most substantial branches of the tree-of-life, but the relationships are still not well established with mitochondrial genome data. The main reasons have been the absence of sufficient data in several orders and lack of appropriate phylogenetic methods that avoid the systematic errors from compositional and mutational biases in insect mitochondrial genomes. In this study, we assembled the richest taxon sampling of Holometabola to date (199 species in 11 orders), and analyzed both nucleotide and amino acid data sets using several methods. We find the standard Bayesian inference and maximum-likelihood analyses were strongly affected by systematic biases, but the site-heterogeneous mixture model implemented in PhyloBayes avoided the false grouping of unrelated taxa exhibiting similar base composition and accelerated evolutionary rate. The inclusion of rRNA genes and removal of fast-evolving sites with the observed variability sorting method for identifying sites deviating from the mean rates improved the phylogenetic inferences under a site-heterogeneous model, correctly recovering most deep branches of the Holometabola phylogeny. We suggest that the use of mitochondrial genome data for resolving deep phylogenetic relationships requires an assessment of the potential impact of substitutional saturation and compositional biases through data deletion strategies and by using site-heterogeneous mixture models. Our study suggests a practical approach for how to use densely sampled mitochondrial genome data in phylogenetic analyses. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework.

    Science.gov (United States)

    Yang, Hai; Wei, Qiang; Zhong, Xue; Yang, Hushan; Li, Bingshan

    2017-02-15

    Comprehensive catalogue of genes that drive tumor initiation and progression in cancer is key to advancing diagnostics, therapeutics and treatment. Given the complexity of cancer, the catalogue is far from complete yet. Increasing evidence shows that driver genes exhibit consistent aberration patterns across multiple-omics in tumors. In this study, we aim to leverage complementary information encoded in each of the omics data to identify novel driver genes through an integrative framework. Specifically, we integrated mutations, gene expression, DNA copy numbers, DNA methylation and protein abundance, all available in The Cancer Genome Atlas (TCGA) and developed iDriver, a non-parametric Bayesian framework based on multivariate statistical modeling to identify driver genes in an unsupervised fashion. iDriver captures the inherent clusters of gene aberrations and constructs the background distribution that is used to assess and calibrate the confidence of driver genes identified through multi-dimensional genomic data. We applied the method to 4 cancer types in TCGA and identified candidate driver genes that are highly enriched with known drivers. (e.g.: P < 3.40 × 10 -36 for breast cancer). We are particularly interested in novel genes and observed multiple lines of supporting evidence. Using systematic evaluation from multiple independent aspects, we identified 45 candidate driver genes that were not previously known across these 4 cancer types. The finding has important implications that integrating additional genomic data with multivariate statistics can help identify cancer drivers and guide the next stage of cancer genomics research. The C ++ source code is freely available at https://medschool.vanderbilt.edu/cgg/ . hai.yang@vanderbilt.edu or bingshan.li@Vanderbilt.Edu. Supplementary data are available at Bioinformatics online.

  2. Genome scan for quantitative trait loci influencing HDL levels: evidence for multilocus inheritance in familial combined hyperlipidemia.

    Science.gov (United States)

    Gagnon, France; Jarvik, Gail P; Badzioch, Michael D; Motulsky, Arno G; Brunzell, John D; Wijsman, Ellen M

    2005-09-01

    Several genome scans in search of high-density lipoprotein (HDL) quantitative trait loci (QTLs) have been performed. However, to date the actual identification of genes implicated in the regulation of common forms of HDL abnormalities remains unsuccessful. This may be due, in part, to the oligogenic and multivariate nature of HDL regulation, and potentially, pleiotropy affecting HDL and other lipid-related traits. Using a Bayesian Markov Chain Monte Carlo (MCMC) approach, we recently provided evidence of linkage of HDL level variation to the APOA1-C3-A4-A5 gene complex, in familial combined hyperlipidemia pedigrees, with an estimated number of two to three large QTLs remaining to be identified. We also presented results consistent with pleiotropy affecting HDL and triglycerides at the APOA1-C3-A4-A5 gene complex. Here we use the same MCMC analytic strategy, which allows for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. We now present results from a genome scan in search for the additional HDL QTLs in these pedigrees. We provide evidence of linkage for additional HDL QTLs on chromosomes 3p14 and 13q32, with results on chromosome 3 further supported by maximum parametric and variance component LOD scores of 3.0 and 2.6, respectively. Weaker evidence of linkage was also obtained for 7q32, 12q12, 14q31-32 and 16q23-24.

  3. Estimating demographic parameters from large-scale population genomic data using Approximate Bayesian Computation

    Directory of Open Access Journals (Sweden)

    Li Sen

    2012-03-01

    Full Text Available Abstract Background The Approximate Bayesian Computation (ABC approach has been used to infer demographic parameters for numerous species, including humans. However, most applications of ABC still use limited amounts of data, from a small number of loci, compared to the large amount of genome-wide population-genetic data which have become available in the last few years. Results We evaluated the performance of the ABC approach for three 'population divergence' models - similar to the 'isolation with migration' model - when the data consists of several hundred thousand SNPs typed for multiple individuals by simulating data from known demographic models. The ABC approach was used to infer demographic parameters of interest and we compared the inferred values to the true parameter values that was used to generate hypothetical "observed" data. For all three case models, the ABC approach inferred most demographic parameters quite well with narrow credible intervals, for example, population divergence times and past population sizes, but some parameters were more difficult to infer, such as population sizes at present and migration rates. We compared the ability of different summary statistics to infer demographic parameters, including haplotype and LD based statistics, and found that the accuracy of the parameter estimates can be improved by combining summary statistics that capture different parts of information in the data. Furthermore, our results suggest that poor choices of prior distributions can in some circumstances be detected using ABC. Finally, increasing the amount of data beyond some hundred loci will substantially improve the accuracy of many parameter estimates using ABC. Conclusions We conclude that the ABC approach can accommodate realistic genome-wide population genetic data, which may be difficult to analyze with full likelihood approaches, and that the ABC can provide accurate and precise inference of demographic parameters from

  4. Genome scan of M. tuberculosis infection and disease in Ugandans.

    Science.gov (United States)

    Stein, Catherine M; Zalwango, Sarah; Malone, LaShaunda L; Won, Sungho; Mayanja-Kizza, Harriet; Mugerwa, Roy D; Leontiev, Dmitry V; Thompson, Cheryl L; Cartier, Kevin C; Elston, Robert C; Iyengar, Sudha K; Boom, W Henry; Whalen, Christopher C

    2008-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFalpha) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10(-3)) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal alpha = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFalpha p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFalpha p = 0.002). These results confirm not

  5. Genome scan of M. tuberculosis infection and disease in Ugandans.

    Directory of Open Access Journals (Sweden)

    Catherine M Stein

    Full Text Available Tuberculosis (TB, caused by Mycobacterium tuberculosis (Mtb, is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-; this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFalpha expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate. We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10(-3 was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002. We also observed linkage at the nominal alpha = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02, IL-1 complex (TB p = 0.01, IL12BR2 (TNFalpha p = 0.006, IL12A (TB p = 0.02 and IFNGR2 (TNFalpha p = 0.002. These results confirm

  6. Genome scan for parent-of-origin QTL effects on bovine growth and carcass traits

    NARCIS (Netherlands)

    Imumorin, I.G.; Kim, B.; Li, Y.; Koning, de D.J.; Arendonk, van J.A.M.; Donato, S.

    2011-01-01

    Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus × Brahman cattle crossbreds. We

  7. Whole Genome PCR Scanning (WGPS) of C. burnetii strains from ruminants

    NARCIS (Netherlands)

    Sidi-Boumedine, Karim; Adam, Gilbert; Angen, Oysten; Aspán, A.; Bossers, A.; Roest, H.I.J.; Prigent, Myriam; Thiéry, R.; Rousset, Elodie

    2015-01-01

    Coxiella burnetii is the causative agent of Q fever, a zoonosis that spreads from ruminants to humans via the inhalation of aerosols contaminated by livestock's birth products. This study aimed to compare the genomes of strains isolated from ruminants by “Whole Genome PCR Scanning (WGPS)” in order t

  8. Genome scan for parent-of-origin QTL effects on bovine growth and carcass traits

    NARCIS (Netherlands)

    Imumorin, I.G.; Kim, B.; Li, Y.; Koning, de D.J.; Arendonk, van J.A.M.; Donato, S.

    2011-01-01

    Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus × Brahman cattle crossbreds. We ident

  9. Exploring neighborhood inequality in female breast cancer incidence in Tehran using Bayesian spatial models and a spatial scan statistic.

    Science.gov (United States)

    Ayubi, Erfan; Mansournia, Mohammad Ali; Motlagh, Ali Ghanbari; Mosavi-Jarrahi, Alireza; Hosseini, Ali; Yazdani, Kamran

    2017-01-01

    The aim of this study was to explore the spatial pattern of female breast cancer (BC) incidence at the neighborhood level in Tehran, Iran. The present study included all registered incident cases of female BC from March 2008 to March 2011. The raw standardized incidence ratio (SIR) of BC for each neighborhood was estimated by comparing observed cases relative to expected cases. The estimated raw SIRs were smoothed by a Besag, York, and Mollie spatial model and the spatial empirical Bayesian method. The purely spatial scan statistic was used to identify spatial clusters. There were 4,175 incident BC cases in the study area from 2008 to 2011, of which 3,080 were successfully geocoded to the neighborhood level. Higher than expected rates of BC were found in neighborhoods located in northern and central Tehran, whereas lower rates appeared in southern areas. The most likely cluster of higher than expected BC incidence involved neighborhoods in districts 3 and 6, with an observed-to-expected ratio of 3.92 (p<0.001), whereas the most likely cluster of lower than expected rates involved neighborhoods in districts 17, 18, and 19, with an observed-to-expected ratio of 0.05 (p<0.001). Neighborhood-level inequality in the incidence of BC exists in Tehran. These findings can serve as a basis for resource allocation and preventive strategies in at-risk areas.

  10. Bayesian deconvolution of scanning electron microscopy images using point-spread function estimation and non-local regularization.

    Science.gov (United States)

    Roels, Joris; Aelterman, Jan; De Vylder, Jonas; Hiep Luong; Saeys, Yvan; Philips, Wilfried

    2016-08-01

    Microscopy is one of the most essential imaging techniques in life sciences. High-quality images are required in order to solve (potentially life-saving) biomedical research problems. Many microscopy techniques do not achieve sufficient resolution for these purposes, being limited by physical diffraction and hardware deficiencies. Electron microscopy addresses optical diffraction by measuring emitted or transmitted electrons instead of photons, yielding nanometer resolution. Despite pushing back the diffraction limit, blur should still be taken into account because of practical hardware imperfections and remaining electron diffraction. Deconvolution algorithms can remove some of the blur in post-processing but they depend on knowledge of the point-spread function (PSF) and should accurately regularize noise. Any errors in the estimated PSF or noise model will reduce their effectiveness. This paper proposes a new procedure to estimate the lateral component of the point spread function of a 3D scanning electron microscope more accurately. We also propose a Bayesian maximum a posteriori deconvolution algorithm with a non-local image prior which employs this PSF estimate and previously developed noise statistics. We demonstrate visual quality improvements and show that applying our method improves the quality of subsequent segmentation steps.

  11. Bayesian variable selection in searching for additive and dominant effects in genome-wide data.

    Directory of Open Access Journals (Sweden)

    Tomi Peltola

    Full Text Available Although complex diseases and traits are thought to have multifactorial genetic basis, the common methods in genome-wide association analyses test each variant for association independent of the others. This computational simplification may lead to reduced power to identify variants with small effect sizes and requires correcting for multiple hypothesis tests with complex relationships. However, advances in computational methods and increase in computational resources are enabling the computation of models that adhere more closely to the theory of multifactorial inheritance. Here, a Bayesian variable selection and model averaging approach is formulated for searching for additive and dominant genetic effects. The approach considers simultaneously all available variants for inclusion as predictors in a linear genotype-phenotype mapping and averages over the uncertainty in the variable selection. This leads to naturally interpretable summary quantities on the significances of the variants and their contribution to the genetic basis of the studied trait. We first characterize the behavior of the approach in simulations. The results indicate a gain in the causal variant identification performance when additive and dominant variation are simulated, with a negligible loss of power in purely additive case. An application to the analysis of high- and low-density lipoprotein cholesterol levels in a dataset of 3895 Finns is then presented, demonstrating the feasibility of the approach at the current scale of single-nucleotide polymorphism data. We describe a Markov chain Monte Carlo algorithm for the computation and give suggestions on the specification of prior parameters using commonly available prior information. An open-source software implementing the method is available at http://www.lce.hut.fi/research/mm/bmagwa/ and https://github.com/to-mi/.

  12. Application of Bayesian least absolute shrinkage and selection operator (LASSO) and BayesCπ methods for genomic selection in French Holstein and Montbéliarde breeds.

    Science.gov (United States)

    Colombani, C; Legarra, A; Fritz, S; Guillaume, F; Croiseau, P; Ducrocq, V; Robert-Granié, C

    2013-01-01

    Recently, the amount of available single nucleotide polymorphism (SNP) marker data has considerably increased in dairy cattle breeds, both for research purposes and for application in commercial breeding and selection programs. Bayesian methods are currently used in the genomic evaluation of dairy cattle to handle very large sets of explanatory variables with a limited number of observations. In this study, we applied 2 bayesian methods, BayesCπ and bayesian least absolute shrinkage and selection operator (LASSO), to 2 genotyped and phenotyped reference populations consisting of 3,940 Holstein bulls and 1,172 Montbéliarde bulls with approximately 40,000 polymorphic SNP. We compared the accuracy of the bayesian methods for the prediction of 3 traits (milk yield, fat content, and conception rate) with pedigree-based BLUP, genomic BLUP, partial least squares (PLS) regression, and sparse PLS regression, a variable selection PLS variant. The results showed that the correlations between observed and predicted phenotypes were similar in BayesCπ (including or not pedigree information) and bayesian LASSO for most of the traits and whatever the breed. In the Holstein breed, bayesian methods led to higher correlations than other approaches for fat content and were similar to genomic BLUP for milk yield and to genomic BLUP and PLS regression for the conception rate. In the Montbéliarde breed, no method dominated the others, except BayesCπ for fat content. The better performances of the bayesian methods for fat content in Holstein and Montbéliarde breeds are probably due to the effect of the DGAT1 gene. The SNP identified by the BayesCπ, bayesian LASSO, and sparse PLS regression methods, based on their effect on the different traits of interest, were located at almost the same position on the genome. As the bayesian methods resulted in regressions of direct genomic values on daughter trait deviations closer to 1 than for the other methods tested in this study, bayesian

  13. Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates

    OpenAIRE

    Gautier, Mathieu

    2015-01-01

    In population genomics studies, accounting for the neutral covariance structure across population allele frequencies is critical to improve the robustness of genome-wide scan approaches. Elaborating on the BayEnv model, this study investigates several modeling extensions (i) to improve the estimation accuracy of the population covariance matrix and all the related measures, (ii) to identify significantly overly differentiated SNPs based on a calibration procedure of the XtX statistics, and (i...

  14. Ab initio gene identification: prokaryote genome annotation with GeneScan and GLIMMER

    Indian Academy of Sciences (India)

    Gautam Aggarwal; Ramakrishna Ramaswamy

    2002-02-01

    We compare the annotation of three complete genomes using the ab initio methods of gene identification GeneScan and GLIMMER. The annotation given in GenBank, the standard against which these are compared, has been made using GeneMark. We find a number of novel genes which are predicted by both methods used here, as well as a number of genes that are predicted by GeneMark, but are not identified by either of the nonconsensus methods that we have used. The three organisms studied here are all prokaryotic species with fairly compact genomes. The Fourier measure forms the basis for an efficient non-consensus method for gene prediction, and the algorithm GeneScan exploits this measure. We have bench-marked this program as well as GLIMMER using 3 complete prokaryotic genomes. An effort has also been made to study the limitations of these techniques for complete genome analysis. GeneScan and GLIMMER are of comparable accuracy insofar as gene-identification is concerned, with sensitivities and specificities typically greater than 0.9. The number of false predictions (both positive and negative) is higher for GeneScan as compared to GLIMMER, but in a significant number of cases, similar results are provided by the two techniques. This suggests that there could be some as-yet unidentified additional genes in these three genomes, and also that some of the putative identifications made hitherto might require re-evaluation. All these cases are discussed in detail.

  15. A Genome-wide Pleiotropy Scan for Prostate Cancer Risk

    Science.gov (United States)

    Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I.; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R.; Siddiq, Afshan; Papatheodorou, Stefania I.; Stanford, Janet L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J.; Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Gurrea, Aurelio Barricarte; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J. Michael; Hunter, DavidJ.; Koutros, Stella; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Wacholder, Sholom; Key, Timothy J.; Tsilidis, Konstantinos K

    2014-01-01

    Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10−7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95%CI 1.16–1.27; p = 3.22 × 10−18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86–0.94; p = 2.5 × 10−6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12,95% CI 1.06–1.19; p = 4.67 × 10−5); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did

  16. Accounting for Linkage Disequilibrium in genome scans for selection without individual genotypes: the local score approach.

    Science.gov (United States)

    Fariello, María Inés; Boitard, Simon; Mercier, Sabine; Robelin, David; Faraut, Thomas; Arnould, Cécile; Recoquillay, Julien; Bouchez, Olivier; Salin, Gérald; Dehais, Patrice; Gourichon, David; Leroux, Sophie; Pitel, Frédérique; Leterrier, Christine; SanCristobal, Magali

    2017-04-10

    Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal. Using computer simulations, we demonstrate that this approach detects selection with higher power than several state-of-the-art single marker, windowing or haplotype-based approaches. We illustrate this on two benchmark data sets including individual genotypes, for which we obtain similar results with the local score and one haplotype-based approach. Finally, we apply the local score approach to Pool-Seq data obtained from a divergent selection experiment on behavior in quail, and obtain precise and biologically coherent selection signals: while competing methods fail to highlight any clear selection signature, our method detects several regions involving genes known to act on social responsiveness or autistic traits. Although we focus here on the detection of positive selection from multiple population data, the local score approach is general and can be applied to other genome scans for selection or other genome-wide analyses such as GWAS. This article is protected by copyright. All rights reserved.

  17. Robustness of genome-wide scanning using archived dried blood spot samples as a DNA source

    Directory of Open Access Journals (Sweden)

    Børglum Anders D

    2011-07-01

    Full Text Available Abstract Background The search to identify disease-susceptible genes requires access to biological material from numerous well-characterized subjects. Archived residual dried blood spot (DBS samples, also known as Guthrie cards, from national newborn screening programs may provide a DNA source for entire populations. Combined with clinical information from medical registries, DBS samples could provide a rich source for productive research. However, the amounts of DNA which can be extracted from these precious samples are minute and may be prohibitive for numerous genotypings. Previously, we demonstrated that DBS DNA can be whole-genome amplified and used for reliable genetic analysis on different platforms, including genome-wide scanning arrays. However, it remains unclear whether this approach is workable on a large sample scale. We examined the robustness of using DBS samples for whole-genome amplification following genome-wide scanning, using arrays from Illumina and Affymetrix. Results This study is based on 4,641 DBS samples from the Danish Newborn Screening Biobank, extracted for three separate genome-wide association studies. The amount of amplified DNA was significantly (P Conclusion Our study indicates that archived DBS samples from the Danish Newborn Screening Biobank represent a reliable resource of DNA for whole-genome amplification and subsequent genome-wide association studies. With call-rates equivalent to high quality DNA samples, our results point to new opportunities for using the neonatal biobanks available worldwide in the hunt for genetic components of disease.

  18. Whole genome scan to detect quantitative trait loci for bovine milk protein composition

    NARCIS (Netherlands)

    Schopen, G.C.B.; Koks, P.D.; Arendonk, van J.A.M.; Bovenhuis, H.; Visker, M.H.P.W.

    2009-01-01

    The objective of this study was to perform a whole genome scan to detect quantitative trait loci (QTL) for milk protein composition in 849 Holstein–Friesian cows originating from seven sires. One morning milk sample was analysed for the major milk proteins using capillary zone electrophoresis. A gen

  19. Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Zhou, Kaixin; Dempfle, Astrid; Arcos-Burgos, Mauricio; Bakker, Steven C; Banaschewski, Tobias; Biederman, Joseph; Buitelaar, Jan; Castellanos, F Xavier; Doyle, Alysa; Ebstein, Richard P; Ekholm, Jenny; Forabosco, Paola; Franke, Barbara; Freitag, Christine; Friedel, Susann; Gill, Michael; Hebebrand, Johannes; Hinney, Anke; Jacob, Christian; Lesch, Klaus Peter; Loo, Sandra K; Lopera, Francisco; McCracken, James T; McGough, James J; Meyer, Jobst; Mick, Eric; Miranda, Ana; Muenke, Maximilian; Mulas, Fernando; Nelson, Stanley F; Nguyen, T Trang; Oades, Robert D; Ogdie, Matthew N; Palacio, Juan David; Pineda, David; Reif, Andreas; Renner, Tobias J; Roeyers, Herbert; Romanos, Marcel; Rothenberger, Aribert; Schäfer, Helmut; Sergeant, Joseph; Sinke, Richard J; Smalley, Susan L; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; van der Meulen, Emma; Walitza, Susanne; Warnke, Andreas; Lewis, Cathryn M; Faraone, Stephen V; Asherson, Philip

    2008-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, th

  20. Genetic dissection of Al tolerance QTLs in the maize genome by high density SNP scan

    Science.gov (United States)

    Aluminum (Al) toxicity is an important limitation to food security in the tropical and subtropical regions. High Al saturation in acid soils limits root development and its ability to uptake water and nutrients. In this study, we present a genome scan for Al tolerance loci with over 50,000 GBS-based...

  1. A novel scan statistics approach for clustering identification and comparison in binary genomic data.

    Science.gov (United States)

    Pellin, Danilo; Di Serio, Clelia

    2016-09-22

    In biomedical research a relevant issue is to identify time intervals or portions of a n-dimensional support where a particular event of interest is more likely to occur than expected. Algorithms that require to specify a-priori number/dimension/length of clusters assumed for the data suffer from a high degree of arbitrariness whenever no precise information are available, and this may strongly affect final estimation on parameters. Within this framework, spatial scan-statistics have been proposed in the literature, representing a valid non-parametric alternative. We adapt the so called Bernoulli-model scan statistic to the genomic field and we propose a multivariate extension, named Relative Scan Statistics, for the comparison of two series of Bernoulli r.v. defined over a common support, with the final goal of highlighting unshared event rate variations. Using a probabilistic approach based on success probability estimates and comparison (likelihood based), we can exploit an hypothesis testing procedure to identify clusters and relative clusters. Both the univariate and the novel multivariate extension of the scan statistic confirm previously published findings. The method described in the paper represents a challenging application of scan statistics framework to problem related to genomic data. From a biological perspective, these tools offer the possibility to clinicians and researcher to improve their knowledge on viral vectors integrations process, allowing to focus their attention to restricted over-targeted portion of the genome.

  2. An EST-based genome scan using 454 sequencing in the marine snail Littorina saxatilis.

    Science.gov (United States)

    Galindo, J; Grahame, J W; Butlin, R K

    2010-09-01

    Genome scans have been used in the studies of ecological speciation to find genomic regions ('outlier loci') showing reduced gene flow between divergent populations/species. High-throughput sequencing ('454') offers new opportunities in this field via transcriptome sequencing. Divergent ecotypes of the marine gastropod Littorina saxatilis represent a good example of incipient ecological speciation. We performed a 454-based genome scan between H and M ecotypes of L. saxatilis from the British Isles using cDNA of pooled individuals. Allele frequencies were calculated for 2454 single nucleotide polymorphisms (SNPs), within 572 contigs, and 7% of loci were detected as outliers. Functional annotation of the contigs containing outlier SNPs showed that they included shell matrix and muscle proteins (lithostathine, mucin, titin), proteins involved in energetic metabolism (arginine kinase, NADH dehydrogenase) and reverse transcriptases. Follow-up investigations into these proteins and unannotated outliers will be a promising route in the study of ecological speciation in L. saxatilis.

  3. Development of Genome-Wide Scan for Selection Signature in Farm Animals

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-guang

    2013-01-01

    Identifying targets of positive selection in farm animals has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to systematically interrogate the entire genome for signatures of selection. This review described important recent results derived from the application of genome-wide scan to the study of genetic changes in farm animals. These included findings of regions of the genome that showed breed differentiation, evidence of selective sweeps within individual genomes and signatures of demographic events. Particular attention is focused on the study of the implications for domestication. To date, sixteen genome-wide scans for recent or ongoing positive selection have been performed in farm animals. A key challenge is to begin synthesizing these newly constructed maps of selection into a coherent narrative of animal breed evolutionary history and derive a deeper mechanistic understanding of how animal populations improve or evolve. The major insights from the surveyed studies are highlighted and directions for future study are suggested.

  4. Genome-wide scans using archived neonatal dried blood spot samples

    Directory of Open Access Journals (Sweden)

    Wiuf Carsten

    2009-07-01

    Full Text Available Abstract Background Identification of disease susceptible genes requires access to DNA from numerous well-characterised subjects. Archived residual dried blood spot samples from national newborn screening programs may provide DNA from entire populations and medical registries the corresponding clinical information. The amount of DNA available in these samples is however rarely sufficient for reliable genome-wide scans, and whole-genome amplification may thus be necessary. This study assess the quality of DNA obtained from different amplification protocols by evaluating fidelity and robustness of the genotyping of 610,000 single nucleotide polymorphisms, using the Illumina Infinium HD Human610-Quad BeadChip. Whole-genome amplified DNA from 24 neonatal dried blood spot samples stored between 15 to 25 years was tested, and high-quality genomic DNA from 8 of the same individuals was used as reference. Results Using 3.2 mm disks from dried blood spot samples the optimal DNA-extraction and amplification protocol resulted in call-rates between 99.15% – 99.73% (mean 99.56%, N = 16, and conflicts with reference DNA in only three per 10,000 genotype calls. Conclusion Whole-genome amplified DNA from archived neonatal dried blood spot samples can be used for reliable genome-wide scans and is a cost-efficient alternative to collecting new samples.

  5. A genome-wide SNP scan accelerates trait-regulatory genomic loci identification in chickpea

    Science.gov (United States)

    Kujur, Alice; Bajaj, Deepak; Upadhyaya, Hari D.; Das, Shouvik; Ranjan, Rajeev; Shree, Tanima; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C.L.L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    We identified 44844 high-quality SNPs by sequencing 92 diverse chickpea accessions belonging to a seed and pod trait-specific association panel using reference genome- and de novo-based GBS (genotyping-by-sequencing) assays. A GWAS (genome-wide association study) in an association panel of 211, including the 92 sequenced accessions, identified 22 major genomic loci showing significant association (explaining 23–47% phenotypic variation) with pod and seed number/plant and 100-seed weight. Eighteen trait-regulatory major genomic loci underlying 13 robust QTLs were validated and mapped on an intra-specific genetic linkage map by QTL mapping. A combinatorial approach of GWAS, QTL mapping and gene haplotype-specific LD mapping and transcript profiling uncovered one superior haplotype and favourable natural allelic variants in the upstream regulatory region of a CesA-type cellulose synthase (Ca_Kabuli_CesA3) gene regulating high pod and seed number/plant (explaining 47% phenotypic variation) in chickpea. The up-regulation of this superior gene haplotype correlated with increased transcript expression of Ca_Kabuli_CesA3 gene in the pollen and pod of high pod/seed number accession, resulting in higher cellulose accumulation for normal pollen and pollen tube growth. A rapid combinatorial genome-wide SNP genotyping-based approach has potential to dissect complex quantitative agronomic traits and delineate trait-regulatory genomic loci (candidate genes) for genetic enhancement in crop plants, including chickpea. PMID:26058368

  6. The first complete mitochondrial genome from Bostrychus genus (Bostrychus sinensis) and partitioned Bayesian analysis of Eleotridae fish phylogeny

    Indian Academy of Sciences (India)

    Tao Wei; Xiao Xiao Jin; Tian Jun Xu

    2013-08-01

    To understand the phylogenetic position of Bostrychus sinensis in Eleotridae and the phylogenetic relationships of the family, we determined the nucleotide sequence of the mitochondrial (mt) genome of Bostrychus sinensis. It is the first complete mitochondrial genome sequence of Bostrychus genus. The entire mtDNA sequence was 16508 bp in length with a standard set of 13 protein-coding genes, 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs) and a noncoding control region. The mitochondrial genome of B. sinensis had common features with those of other bony fishes with respect to gene arrangement, base composition, and tRNA structures. Phylogenetic hypotheses within Eleotridae fish have been controversial at the genus level. We used the mitochondrial cytochrome b (cytb) gene sequence to examine phylogenetic relationships of Eleotridae by using partitioned Bayesian method. When the specific models and parameter estimates were presumed for partitioning the total data, the harmonic mean –lnL was improved. The phylogenetic analysis supported the monophyly of Hypseleotris and Gobiomorphs. In addition, the Bostrychus were most closely related to Ophiocara, and the Philypnodon is also the sister to Microphlypnus, based on the current datasets. Further, extensive taxonomic sampling and more molecular information are needed to confirm the phylogenetic relationships in Eleotridae.

  7. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.

    OpenAIRE

    Norman, R. A.; Tataranni, P A; Pratley, R; Thompson, D B; Hanson, R. L.; Prochazka, M; Baier, L; Ehm, M. G.; Sakul, H; Foroud, T; Garvey, W. T.; Burns, D.; Knowler, W. C.; Bennett, P. H.; Bogardus, C

    1998-01-01

    An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidatio...

  8. Bayesian prediction of bacterial growth temperature range based on genome sequences

    DEFF Research Database (Denmark)

    Jensen, Dan Børge; Vesth, Tammi Camilla; Hallin, Peter Fischer

    2012-01-01

    on a genomic sequence, would thus allow for an efficient and targeted search for production organisms, reducing the need for culturing experiments. Results: This study found a total of 40 protein families useful for distinction between three thermophilicity classes (thermophiles, mesophiles and psychrophiles...... and psychrophilic adapted bacterial genomes....

  9. Bayesian molecular clock dating of species divergences in the genomics era.

    Science.gov (United States)

    dos Reis, Mario; Donoghue, Philip C J; Yang, Ziheng

    2016-02-01

    Five decades have passed since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics and studying the macroevolutionary process of speciation and extinction to estimating a timescale for life on Earth.

  10. Non-random mate choice in humans: insights from a genome scan.

    Science.gov (United States)

    Laurent, R; Toupance, B; Chaix, R

    2012-02-01

    Little is known about the genetic factors influencing mate choice in humans. Still, there is evidence for non-random mate choice with respect to physical traits. In addition, some studies suggest that the Major Histocompatibility Complex may affect pair formation. Nowadays, the availability of high density genomic data sets gives the opportunity to scan the genome for signatures of non-random mate choice without prior assumptions on which genes may be involved, while taking into account socio-demographic factors. Here, we performed a genome scan to detect extreme patterns of similarity or dissimilarity among spouses throughout the genome in three populations of African, European American, and Mexican origins from the HapMap 3 database. Our analyses identified genes and biological functions that may affect pair formation in humans, including genes involved in skin appearance, morphogenesis, immunity and behaviour. We found little overlap between the three populations, suggesting that the biological functions potentially influencing mate choice are population specific, in other words are culturally driven. Moreover, whenever the same functional category of genes showed a significant signal in two populations, different genes were actually involved, which suggests the possibility of evolutionary convergences.

  11. High-throughput DNA Stretching in Continuous Elongational Flow for Genome Sequence Scanning

    Science.gov (United States)

    Meltzer, Robert; Griffis, Joshua; Safranovitch, Mikhail; Malkin, Gene; Cameron, Douglas

    2014-03-01

    Genome Sequence Scanning (GSS) identifies and compares bacterial genomes by stretching long (60 - 300 kb) genomic DNA restriction fragments and scanning for site-selective fluorescent probes. Practical application of GSS requires: 1) high throughput data acquisition, 2) efficient DNA stretching, 3) reproducible DNA elasticity in the presence of intercalating fluorescent dyes. GSS utilizes a pseudo-two-dimensional micron-scale funnel with convergent sheathing flows to stretch one molecule at a time in continuous elongational flow and center the DNA stream over diffraction-limited confocal laser excitation spots. Funnel geometry has been optimized to maximize throughput of DNA within the desired length range (>10 million nucleobases per second). A constant-strain detection channel maximizes stretching efficiency by applying a constant parabolic tension profile to each molecule, minimizing relaxation and flow-induced tumbling. The effect of intercalator on DNA elasticity is experimentally controlled by reacting one molecule of DNA at a time in convergent sheathing flows of the dye. Derivations of accelerating flow and non-linear tension distribution permit alignment of detected fluorescence traces to theoretical templates derived from whole-genome sequence data.

  12. Genomic scanning using AFLP to detect loci under selection in the moss Funaria hygrometrica along a climate gradient in the Sierra Nevada Mountains, Spain.

    Science.gov (United States)

    Magdy, M; Werner, O; McDaniel, S F; Goffinet, B; Ros, R M

    2016-03-01

    The common cord moss Funaria hygrometrica has a worldwide distribution and thrives in a wide variety of environments. Here, we studied the genetic diversity in F. hygrometrica along an abiotic gradient in the Mediterranean high mountain of Sierra Nevada (Spain) using a genome scan method. Eighty-four samples from 17 locations from 24 to 2700 m were fingerprinted based on their amplified fragment length polymorphism (AFLP) banding pattern. Using PCA and Bayesian inference we found that the genetic diversity was structured in three or four clusters, respectively. Using a genome scan method we identified 13 outlier loci, which showed a signature of positive selection. Partial Mantel tests were performed between the Euclidean distance matrices of geographic and climatic variables, versus the pair-wise genetic distance of the AFLP dataset and AFLP-positive outliers dataset. AFLP-positive outlier data were significantly correlated with the gradient of the climatic variables, suggesting adaptive variation among populations of F. hygrometrica along the Sierra Nevada Mountains. We highlight the additional analyses necessary to identify the nature of these loci, and their biological role in the adaptation process.

  13. Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach.

    Directory of Open Access Journals (Sweden)

    Simon Boitard

    2016-03-01

    Full Text Available Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey, PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles.

  14. A Bayesian hidden Markov model for motif discovery through joint modeling of genomic sequence and ChIP-chip data.

    Science.gov (United States)

    Gelfond, Jonathan A L; Gupta, Mayetri; Ibrahim, Joseph G

    2009-12-01

    We propose a unified framework for the analysis of chromatin (Ch) immunoprecipitation (IP) microarray (ChIP-chip) data for detecting transcription factor binding sites (TFBSs) or motifs. ChIP-chip assays are used to focus the genome-wide search for TFBSs by isolating a sample of DNA fragments with TFBSs and applying this sample to a microarray with probes corresponding to tiled segments across the genome. Present analytical methods use a two-step approach: (i) analyze array data to estimate IP-enrichment peaks then (ii) analyze the corresponding sequences independently of intensity information. The proposed model integrates peak finding and motif discovery through a unified Bayesian hidden Markov model (HMM) framework that accommodates the inherent uncertainty in both measurements. A Markov chain Monte Carlo algorithm is formulated for parameter estimation, adapting recursive techniques used for HMMs. In simulations and applications to a yeast RAP1 dataset, the proposed method has favorable TFBS discovery performance compared to currently available two-stage procedures in terms of both sensitivity and specificity.

  15. A two step Bayesian approach for genomic prediction of breeding values

    DEFF Research Database (Denmark)

    Mahdi Shariati, Mohammad; Sørensen, Peter; Janss, Luc

    2012-01-01

    . A better alternative could be to form clusters of markers with similar effects where markers in a cluster have a common variance. Therefore, the influence of each marker group of size p on the posterior distribution of the marker variances will be p df. Methods: The simulated data from the 15th QTL...... of predicted breeding values. However, the accuracies of predicted breeding values were lower than Bayesian methods with marker specific variances. Conclusions: Grouping markers is less flexible than allowing each marker to have a specific marker variance but, by grouping, the power to estimate marker...... variances increases. A prior knowledge of the genetic architecture of the trait is necessary for clustering markers and appropriate prior parameterization...

  16. Genome scan for nonadditive heterotic trait loci reveals mainly underdominant effects in Saccharomyces cerevisiae.

    Science.gov (United States)

    Laiba, Efrat; Glikaite, Ilana; Levy, Yael; Pasternak, Zohar; Fridman, Eyal

    2016-04-01

    The overdominant model of heterosis explains the superior phenotype of hybrids by synergistic allelic interaction within heterozygous loci. To map such genetic variation in yeast, we used a population doubling time dataset of Saccharomyces cerevisiae 16 × 16 diallel and searched for major contributing heterotic trait loci (HTL). Heterosis was observed for the majority of hybrids, as they surpassed their best parent growth rate. However, most of the local heterozygous loci identified by genome scan were surprisingly underdominant, i.e., reduced growth. We speculated that in these loci adverse effects on growth resulted from incompatible allelic interactions. To test this assumption, we eliminated these allelic interactions by creating hybrids with local hemizygosity for the underdominant HTLs, as well as for control random loci. Growth of hybrids was indeed elevated for most hemizygous to HTL genes but not for control genes, hence validating the results of our genome scan. Assessing the consequences of local heterozygosity by reciprocal hemizygosity and allele replacement assays revealed the influence of genetic background on the underdominant effects of HTLs. Overall, this genome-wide study on a multi-parental hybrid population provides a strong argument against single gene overdominance as a major contributor to heterosis, and favors the dominance complementation model.

  17. A genome-wide scan for Eysenckian personality dimensions in adolescent twin sibships: psychoticism, extraversion, neuroticism, and lie.

    Science.gov (United States)

    Gillespie, Nathan A; Zhu, Gu; Evans, David M; Medland, Sarah E; Wright, Margie J; Martin, Nick G

    2008-12-01

    We report the first genome-wide scan of adolescent personality. We conducted a genome-wide scan to detect linkage for measures of adolescent Psychoticism, Extraversion, Neuroticism, and Lie from the Junior Eysenck Personality Questionnaire. Data are based on 1,280 genotyped Australian adolescent twins and their siblings. The highest linkage peaks were found on chromosomes 16 and 19 for Neuroticism, on chromosomes 1, 7, 10, 13 m, and 18 for Psychoticism, and on chromosomes 2 and 3 for Extraversion.

  18. Genome scan for parent-of-origin QTL effects on bovine growth and carcass traits

    Directory of Open Access Journals (Sweden)

    Ikhide G. Imumorin

    2011-07-01

    Full Text Available Parent-of-origin effects (POE such as genomic imprinting influence growth and body composition in livestock, rodents and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL with POE on growth and carcass traits in Angus x Brahman cattle crossbreds. We identified 24 POE-QTL on 15 Bos taurus autosomes (BTAs of which 6 were significant at 5% genome-wide level and 18 at the 5% chromosome-wide significance level. Six QTL were paternally expressed while 15 were maternally expressed. Three QTL influencing post-weaning growth map to the proximal end of BTA2 [linkage region of 0 – 9 cM; genomic region of 5.0 – 10.8 Mb], for which only one imprinted orthologue is known so far in the human and mouse genomes, and therefore may potentially represent a novel imprinted region. The detected QTL individually explained 1.4% ~ 5.1% of each trait’s phenotypic variance. Comparative in-silico analysis of bovine genomic locations show that 32 out of 1,442 known mammalian imprinted genes from human and mouse homologues map to the identified QTL regions. Although several of the 32 genes have been associated with quantitative traits in cattle, only 2 (GNAS and PEG3 have experimental proof of being imprinted in cattle. These results lend additional support to recent reports that POE on quantitative traits in mammals may be more common than previously thought, and strengthen the need to identify and experimentally validate cattle orthologues of imprinted genes so as to investigate their effects on quantitative traits.

  19. Genome Scan for Parent-of-Origin QTL Effects on Bovine Growth and Carcass Traits.

    Science.gov (United States)

    Imumorin, Ikhide G; Kim, Eun-Hee; Lee, Yun-Mi; De Koning, Dirk-Jan; van Arendonk, Johan A; De Donato, Marcos; Taylor, Jeremy F; Kim, Jong-Joo

    2011-01-01

    Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus × Brahman cattle crossbreds. We identified 24 POE-QTL on 15 Bos taurus autosomes (BTAs) of which six were significant at 5% genome-wide (GW) level and 18 at the 5% chromosome-wide (CW) significance level. Six QTL were paternally expressed while 15 were maternally expressed. Three QTL influencing post-weaning growth map to the proximal end of BTA2 (linkage region of 0-9 cM; genomic region of 5.0-10.8 Mb), for which only one imprinted ortholog is known so far in the human and mouse genomes, and therefore may potentially represent a novel imprinted region. The detected QTL individually explained 1.4 ∼ 5.1% of each trait's phenotypic variance. Comparative in silico analysis of bovine genomic locations show that 32 out of 1,442 known mammalian imprinted genes from human and mouse homologs map to the identified QTL regions. Although several of the 32 genes have been associated with quantitative traits in cattle, only two (GNAS and PEG3) have experimental proof of being imprinted in cattle. These results lend additional support to recent reports that POE on quantitative traits in mammals may be more common than previously thought, and strengthen the need to identify and experimentally validate cattle orthologs of imprinted genes so as to investigate their effects on quantitative traits.

  20. Combined genome scans for body stature in 6,602 European twins

    DEFF Research Database (Denmark)

    Perola, Markus; Sammalisto, Sampo; Hiekkalinna, Tero

    2007-01-01

    Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists...... of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height......) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were...

  1. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Nielsen, M; Lamberth, K;

    2004-01-01

    of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.......An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T-lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)-restricted presentation of SARS-derived peptide epitopes......-CoV) was isolated and full-length sequenced (Marra et al., Science 2003: 300: 1399-404). Here, we have combined advanced bioinformatics and high-throughput immunology to perform an HLA supertype-, genome-wide scan for SARS-specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99...

  2. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.;

    2004-01-01

    of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.......An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T-lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)-restricted presentation of SARS-derived peptide epitopes......-CoV) was isolated and full-length sequenced (Marra et al., Science 2003: 300: 1399404). Here, we have combined advanced bioinformatics and high-throughput immunology to perform an HLA supertype-, genome-wide scan for SARS-specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99...

  3. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    Science.gov (United States)

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  4. A comparison in association and linkage genome-wide scans for alcoholism susceptibility genes using single-nucleotide polymorphisms.

    Science.gov (United States)

    Chiu, Yen-Feng; Liu, Su-Yun; Tsai, Ya-Yu

    2005-12-30

    We conducted genome-wide linkage scans using both microsatellite and single-nucleotide polymorphism (SNP) markers. Regions showing the strongest evidence of linkage to alcoholism susceptibility genes were identified. Haplotype analyses using a sliding-window approach for SNPs in these regions were performed. In addition, we performed a genome-wide association scan using SNP data. SNPs in these regions with evidence of association (P alcoholism (the most significant SNP had a p-value of 0.030) as those identified from association genomic screening (the most significant SNP had a p-value of 2.0 x 10(-8)).

  5. A Bayesian Approach for Analysis of Whole-Genome Bisulphite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation.

    Science.gov (United States)

    Rackham, Owen J L; Langley, Sarah R; Oates, Thomas; Vradi, Eleni; Harmston, Nathan; Srivastava, Prashant K; Behmoaras, Jacques; Dellaportas, Petros; Bottolo, Leonardo; Petretto, Enrico

    2017-02-17

    DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method's efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1,000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis) and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.

  6. Bayesian inference for genomic data integration reduces misclassification rate in predicting protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Chuanhua Xing

    2011-07-01

    Full Text Available Protein-protein interactions (PPIs are essential to most fundamental cellular processes. There has been increasing interest in reconstructing PPIs networks. However, several critical difficulties exist in obtaining reliable predictions. Noticeably, false positive rates can be as high as >80%. Error correction from each generating source can be both time-consuming and inefficient due to the difficulty of covering the errors from multiple levels of data processing procedures within a single test. We propose a novel Bayesian integration method, deemed nonparametric Bayes ensemble learning (NBEL, to lower the misclassification rate (both false positives and negatives through automatically up-weighting data sources that are most informative, while down-weighting less informative and biased sources. Extensive studies indicate that NBEL is significantly more robust than the classic naïve Bayes to unreliable, error-prone and contaminated data. On a large human data set our NBEL approach predicts many more PPIs than naïve Bayes. This suggests that previous studies may have large numbers of not only false positives but also false negatives. The validation on two human PPIs datasets having high quality supports our observations. Our experiments demonstrate that it is feasible to predict high-throughput PPIs computationally with substantially reduced false positives and false negatives. The ability of predicting large numbers of PPIs both reliably and automatically may inspire people to use computational approaches to correct data errors in general, and may speed up PPIs prediction with high quality. Such a reliable prediction may provide a solid platform to other studies such as protein functions prediction and roles of PPIs in disease susceptibility.

  7. Bayesian inference for genomic data integration reduces misclassification rate in predicting protein-protein interactions.

    Science.gov (United States)

    Xing, Chuanhua; Dunson, David B

    2011-07-01

    Protein-protein interactions (PPIs) are essential to most fundamental cellular processes. There has been increasing interest in reconstructing PPIs networks. However, several critical difficulties exist in obtaining reliable predictions. Noticeably, false positive rates can be as high as >80%. Error correction from each generating source can be both time-consuming and inefficient due to the difficulty of covering the errors from multiple levels of data processing procedures within a single test. We propose a novel Bayesian integration method, deemed nonparametric Bayes ensemble learning (NBEL), to lower the misclassification rate (both false positives and negatives) through automatically up-weighting data sources that are most informative, while down-weighting less informative and biased sources. Extensive studies indicate that NBEL is significantly more robust than the classic naïve Bayes to unreliable, error-prone and contaminated data. On a large human data set our NBEL approach predicts many more PPIs than naïve Bayes. This suggests that previous studies may have large numbers of not only false positives but also false negatives. The validation on two human PPIs datasets having high quality supports our observations. Our experiments demonstrate that it is feasible to predict high-throughput PPIs computationally with substantially reduced false positives and false negatives. The ability of predicting large numbers of PPIs both reliably and automatically may inspire people to use computational approaches to correct data errors in general, and may speed up PPIs prediction with high quality. Such a reliable prediction may provide a solid platform to other studies such as protein functions prediction and roles of PPIs in disease susceptibility.

  8. Analyzing genome-wide association studies with an FDR controlling modification of the Bayesian Information Criterion.

    Science.gov (United States)

    Dolejsi, Erich; Bodenstorfer, Bernhard; Frommlet, Florian

    2014-01-01

    The prevailing method of analyzing GWAS data is still to test each marker individually, although from a statistical point of view it is quite obvious that in case of complex traits such single marker tests are not ideal. Recently several model selection approaches for GWAS have been suggested, most of them based on LASSO-type procedures. Here we will discuss an alternative model selection approach which is based on a modification of the Bayesian Information Criterion (mBIC2) which was previously shown to have certain asymptotic optimality properties in terms of minimizing the misclassification error. Heuristic search strategies are introduced which attempt to find the model which minimizes mBIC2, and which are efficient enough to allow the analysis of GWAS data. Our approach is implemented in a software package called MOSGWA. Its performance in case control GWAS is compared with the two algorithms HLASSO and d-GWASelect, as well as with single marker tests, where we performed a simulation study based on real SNP data from the POPRES sample. Our results show that MOSGWA performs slightly better than HLASSO, where specifically for more complex models MOSGWA is more powerful with only a slight increase in Type I error. On the other hand according to our simulations GWASelect does not at all control the type I error when used to automatically determine the number of important SNPs. We also reanalyze the GWAS data from the Wellcome Trust Case-Control Consortium and compare the findings of the different procedures, where MOSGWA detects for complex diseases a number of interesting SNPs which are not found by other methods.

  9. Analyzing genome-wide association studies with an FDR controlling modification of the Bayesian Information Criterion.

    Directory of Open Access Journals (Sweden)

    Erich Dolejsi

    Full Text Available The prevailing method of analyzing GWAS data is still to test each marker individually, although from a statistical point of view it is quite obvious that in case of complex traits such single marker tests are not ideal. Recently several model selection approaches for GWAS have been suggested, most of them based on LASSO-type procedures. Here we will discuss an alternative model selection approach which is based on a modification of the Bayesian Information Criterion (mBIC2 which was previously shown to have certain asymptotic optimality properties in terms of minimizing the misclassification error. Heuristic search strategies are introduced which attempt to find the model which minimizes mBIC2, and which are efficient enough to allow the analysis of GWAS data. Our approach is implemented in a software package called MOSGWA. Its performance in case control GWAS is compared with the two algorithms HLASSO and d-GWASelect, as well as with single marker tests, where we performed a simulation study based on real SNP data from the POPRES sample. Our results show that MOSGWA performs slightly better than HLASSO, where specifically for more complex models MOSGWA is more powerful with only a slight increase in Type I error. On the other hand according to our simulations GWASelect does not at all control the type I error when used to automatically determine the number of important SNPs. We also reanalyze the GWAS data from the Wellcome Trust Case-Control Consortium and compare the findings of the different procedures, where MOSGWA detects for complex diseases a number of interesting SNPs which are not found by other methods.

  10. Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Gasser Thomas

    2007-07-01

    Full Text Available Abstract Background Genome wide linkage scans have often been successful in the identification of genetic regions containing susceptibility genes for a disease. Meta analysis is used to synthesize information and can even deliver evidence for findings missed by original studies. If researchers are not contributing their data, extracting valid information from publications is technically challenging, but worth the effort. We propose an approach to include data extracted from published figures of genome wide linkage scans. The validity of the extraction was examined on the basis of those 25 markers, for which sufficient information was reported. Monte Carlo simulations were used to take into account the uncertainty in marker position and in linkage test statistic. For the final meta analysis we compared the Genome Search Meta Analysis method (GSMA and the Corrected p-value Meta analysis Method (CPMM. An application to Parkinson's disease is given. Because we had to use secondary data a meta analysis based on original summary values would be desirable. Results Data uncertainty by replicated extraction of marker position is shown to be much smaller than 30 cM, a distance up to which a maximum LOD score may usually be found away from the true locus. The main findings are not impaired by data uncertainty. Conclusion Applying the proposed method a novel linked region for Parkinson's disease was identified on chromosome 14 (p = 0.036. Comparing the two meta analysis methods we found in this analysis more regions of interest being identified by GSMA, whereas CPMM provides stronger evidence for linkage. For further validation of the extraction method comparisons with raw data would be required.

  11. Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease

    Science.gov (United States)

    Rosenberger, Albert; Sharma, Manu; Müller-Myhsok, Bertram; Gasser, Thomas; Bickeböller, Heike

    2007-01-01

    Background Genome wide linkage scans have often been successful in the identification of genetic regions containing susceptibility genes for a disease. Meta analysis is used to synthesize information and can even deliver evidence for findings missed by original studies. If researchers are not contributing their data, extracting valid information from publications is technically challenging, but worth the effort. We propose an approach to include data extracted from published figures of genome wide linkage scans. The validity of the extraction was examined on the basis of those 25 markers, for which sufficient information was reported. Monte Carlo simulations were used to take into account the uncertainty in marker position and in linkage test statistic. For the final meta analysis we compared the Genome Search Meta Analysis method (GSMA) and the Corrected p-value Meta analysis Method (CPMM). An application to Parkinson's disease is given. Because we had to use secondary data a meta analysis based on original summary values would be desirable. Results Data uncertainty by replicated extraction of marker position is shown to be much smaller than 30 cM, a distance up to which a maximum LOD score may usually be found away from the true locus. The main findings are not impaired by data uncertainty. Conclusion Applying the proposed method a novel linked region for Parkinson's disease was identified on chromosome 14 (p = 0.036). Comparing the two meta analysis methods we found in this analysis more regions of interest being identified by GSMA, whereas CPMM provides stronger evidence for linkage. For further validation of the extraction method comparisons with raw data would be required. PMID:17605797

  12. Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs

    Directory of Open Access Journals (Sweden)

    Regan Kelly R

    2010-05-01

    Full Text Available Abstract Background Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog. Results DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 ± 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs. Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks. Conclusions Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.

  13. Use of genomic DNA control features and predicted operon structure in microarray data analysis: ArrayLeaRNA – a Bayesian approach

    Directory of Open Access Journals (Sweden)

    Pin Carmen

    2007-11-01

    Full Text Available Abstract Background Microarrays are widely used for the study of gene expression; however deciding on whether observed differences in expression are significant remains a challenge. Results A computing tool (ArrayLeaRNA has been developed for gene expression analysis. It implements a Bayesian approach which is based on the Gumbel distribution and uses printed genomic DNA control features for normalization and for estimation of the parameters of the Bayesian model and prior knowledge from predicted operon structure. The method is compared with two other approaches: the classical LOWESS normalization followed by a two fold cut-off criterion and the OpWise method (Price, et al. 2006. BMC Bioinformatics. 7, 19, a published Bayesian approach also using predicted operon structure. The three methods were compared on experimental datasets with prior knowledge of gene expression. With ArrayLeaRNA, data normalization is carried out according to the genomic features which reflect the results of equally transcribed genes; also the statistical significance of the difference in expression is based on the variability of the equally transcribed genes. The operon information helps the classification of genes with low confidence measurements. ArrayLeaRNA is implemented in Visual Basic and freely available as an Excel add-in at http://www.ifr.ac.uk/safety/ArrayLeaRNA/ Conclusion We have introduced a novel Bayesian model and demonstrated that it is a robust method for analysing microarray expression profiles. ArrayLeaRNA showed a considerable improvement in data normalization, in the estimation of the experimental variability intrinsic to each hybridization and in the establishment of a clear boundary between non-changing and differentially expressed genes. The method is applicable to data derived from hybridizations of labelled cDNA samples as well as from hybridizations of labelled cDNA with genomic DNA and can be used for the analysis of datasets where

  14. Bayesian reconstruction of disease outbreaks by combining epidemiologic and genomic data.

    Directory of Open Access Journals (Sweden)

    Thibaut Jombart

    2014-01-01

    Full Text Available Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees ("who infected whom" from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS, providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.

  15. Scanning for signatures of geographically restricted selection based on population genomics analysis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Natural selection, as the driving force of human evolution, has direct impact on population differentiation. However, it is still unclear to what extent the genetic differentiation has been caused by natural selection. To explore this question, we performed a genome-wide scan with single nucleotide polymorphism (SNP) data from the International HapMap Project. Single locus FST analysis was applied to assess the frequency difference among populations in autosomes. Based on the empirical distribution of FST, we identified 12669 SNPs correlating to population differentiation and 1853 candidate genes subjected to geographic restricted natural selection. Further interpretation of gene ontogeny revealed 121 categories of biological process with the enrichments of candidate genes. Our results suggest that natural selection may play an important role in human population differentiation. In addition, our analysis provides new clues as well as research methods for our understanding of population differentiation and natural selection.

  16. A genome-wide scan in families with maturity-onset diabetes of the young

    DEFF Research Database (Denmark)

    Frayling, Timothy M; Lindgren, Cecilia M; Chevre, Jean Claude;

    2003-01-01

    Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do...... not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel...... MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage...

  17. A Genome-wide Scan for Selective Sweeps in Racing Horses

    Science.gov (United States)

    Moon, Sunjin; Lee, Jin Woo; Shin, Donghyun; Shin, Kwang-Yun; Kim, Jun; Choi, Ik-Young; Kim, Jaemin; Kim, Heebal

    2015-01-01

    Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2) that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1), pallid (PLDN), and Ras and Rab interactor 2 (RIN2) genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses. PMID:26333666

  18. A Genome-wide Scan for Selective Sweeps in Racing Horses

    Directory of Open Access Journals (Sweden)

    Sunjin Moon

    2015-11-01

    Full Text Available Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2 that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1, pallid (PLDN, and Ras and Rab interactor 2 (RIN2 genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses.

  19. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    Directory of Open Access Journals (Sweden)

    Anouk Georges

    Full Text Available A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  20. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    Science.gov (United States)

    Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

    2013-01-01

    A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  1. Efficient strategies for genome scanning using maximum-likelihood affected-sib-pair analysis

    Energy Technology Data Exchange (ETDEWEB)

    Holmans, P.; Craddock, N. [Univ. of Wales College of Medicine, Cardiff (United Kingdom)

    1997-03-01

    Detection of linkage with a systematic genome scan in nuclear families including an affected sibling pair is an important initial step on the path to cloning susceptibility genes for complex genetic disorders, and it is desirable to optimize the efficiency of such studies. The aim is to maximize power while simultaneously minimizing the total number of genotypings and probability of type I error. One approach to increase efficiency, which has been investigated by other workers, is grid tightening: a sample is initially typed using a coarse grid of markers, and promising results are followed up by use of a finer grid. Another approach, not previously considered in detail in the context of an affected-sib-pair genome scan for linkage, is sample splitting: a portion of the sample is typed in the screening stage, and promising results are followed up in the whole sample. In the current study, we have used computer simulation to investigate the relative efficiency of two-stage strategies involving combinations of both grid tightening and sample splitting and found that the optimal strategy incorporates both approaches. In general, typing half the sample of affected pairs with a coarse grid of markers in the screening stage is an efficient strategy under a variety of conditions. If Hardy-Weinberg equilibrium holds, it is most efficient not to type parents in the screening stage. If Hardy-Weinberg equilibrium does not hold (e.g., because of stratification) failure to type parents in the first stage increases the amount of genotyping required, although the overall probability of type I error is not greatly increased, provided the parents are used in the final analysis. 23 refs., 4 figs., 5 tabs.

  2. A genome scan for quantitative trait loci affecting resistance to Trichostrongylus colubriformis in sheep.

    Science.gov (United States)

    Beh, K J; Hulme, D J; Callaghan, M J; Leish, Z; Lenane, I; Windon, R G; Maddox, J F

    2002-04-01

    A genome linkage scan was carried out using a resource flock of 1029 sheep in six half-sib families. The families were offspring of sires derived by crossing divergent lines of sheep selected for response to challenge with the intestinal parasitic nematode Trichostrongylus colubriformis. All animals in the resource flock were phenotypically assessed for worm resistance soon after weaning using a vaccination/challenge regime. After correcting for fixed effects using a least squares linear model the faecal egg count data obtained following the first challenge and the faecal egg count data obtained after the second challenge were designated Trait 1 and Trait 2, respectively. A total of 472 lambs drawn from the phenotypic extremes of the Trait 2 faecal egg count distribution were genotyped with a panel of 133 microsatellite markers covering all 26 sheep autosomes. Detection of quantitative trait loci (QTL) for each of the faecal egg count traits was determined using interval analysis with the Animap program with recombination rates between markers derived from an existing marker map. No chromosomal regions attained genome-wide significance for QTL influencing either of the traits. However, one region attained chromosome-wide significance and five other regions attained point-wise significance for the presence of QTL affecting parasite resistance.

  3. Identification of the human chromosomal region containing the iridogoniodysgenesis anomaly locus by genomic-mismatch scanning.

    Science.gov (United States)

    Mirzayans, F; Mears, A J; Guo, S W; Pearce, W G; Walter, M A

    1997-01-01

    Genome-mismatch scanning (GMS) is a new method of linkage analysis that rapidly isolates regions of identity between two genomes. DNA molecules from regions of identity by descent from two relatives are isolated based on their ability to form extended mismatch-free heteroduplexes. We have applied this rapid technology to identify the chromosomal region shared by two fifth-degree cousins with autosomal dominant iridogoniodysgenesis anomaly (IGDA), a rare ocular neurocristopathy. Markers on the short arm of human chromosome 6p were recovered, consistent with the results of conventional linkage analysis conducted in parallel, indicating linkage of IGDA to 6p25. Control markers tested on a second human chromosome were not recovered. A GMS error rate of approximately 11% was observed, well within an acceptable range for a rapid, first screening approach, especially since GMS results would be confirmed by family analysis with selected markers from the putative region of identity by descent. These results demonstrate not only the value of this technique in the rapid mapping of human genetic traits, but the first application of GMS to a multicellular organism. Images Figure 2 PMID:9245991

  4. Recovery of known T-cell epitopes by computational scanning of a viral genome

    Science.gov (United States)

    Logean, Antoine; Rognan, Didier

    2002-04-01

    A new computational method (EpiDock) is proposed for predicting peptide binding to class I MHC proteins, from the amino acid sequence of any protein of immunological interest. Starting from the primary structure of the target protein, individual three-dimensional structures of all possible MHC-peptide (8-, 9- and 10-mers) complexes are obtained by homology modelling. A free energy scoring function (Fresno) is then used to predict the absolute binding free energy of all possible peptides to the class I MHC restriction protein. Assuming that immunodominant epitopes are usually found among the top MHC binders, the method can thus be applied to predict the location of immunogenic peptides on the sequence of the protein target. When applied to the prediction of HLA-A*0201-restricted T-cell epitopes from the Hepatitis B virus, EpiDock was able to recover 92% of known high affinity binders and 80% of known epitopes within a filtered subset of all possible nonapeptides corresponding to about one tenth of the full theoretical list. The proposed method is fully automated and fast enough to scan a viral genome in less than an hour on a parallel computing architecture. As it requires very few starting experimental data, EpiDock can be used: (i) to predict potential T-cell epitopes from viral genomes (ii) to roughly predict still unknown peptide binding motifs for novel class I MHC alleles.

  5. Whole genome scan to detect quantitative trait loci for bovine milk protein composition.

    Science.gov (United States)

    Schopen, G C B; Koks, P D; van Arendonk, J A M; Bovenhuis, H; Visker, M H P W

    2009-08-01

    The objective of this study was to perform a whole genome scan to detect quantitative trait loci (QTL) for milk protein composition in 849 Holstein-Friesian cows originating from seven sires. One morning milk sample was analysed for the major milk proteins using capillary zone electrophoresis. A genetic map was constructed with 1341 single nucleotide polymorphisms, covering 2829 centimorgans (cM) and 95% of the cattle genome. The chromosomal regions most significantly related to milk protein composition (P(genome) casein, alpha(S2)-casein, beta-casein and kappa-casein. The QTL on BTA11 was found at 124 cM, and affected beta-lactoglobulin, and the QTL on BTA14 was found at 0 cM, and affected protein percentage. The proportion of phenotypic variance explained by the QTL was 3.6% for beta-casein and 7.9% for kappa-casein on BTA6, 28.3% for beta-lactoglobulin on BTA11, and 8.6% for protein percentage on BTA14. The QTL affecting alpha(S2)-casein on BTA6 and 17 showed a significant interaction. We investigated the extent to which the detected QTL affecting milk protein composition could be explained by known polymorphisms in beta-casein, kappa-casein, beta-lactoglobulin and DGAT1 genes. Correction for these polymorphisms decreased the proportion of phenotypic variance explained by the QTL previously found on BTA6, 11 and 14. Thus, several significant QTL affecting milk protein composition were found, of which some QTL could partially be explained by polymorphisms in milk protein genes.

  6. A genome scan for quantitative trait loci affecting body conformation traits in Spanish Churra dairy sheep.

    Science.gov (United States)

    Gutiérrez-Gil, B; Alvarez, L; de la Fuente, L F; Sanchez, J P; San Primitivo, F; Arranz, J J

    2011-08-01

    A genome scan for chromosomal regions influencing body conformation traits was conducted for a population of Spanish Churra dairy sheep following a daughter design. A total of 739 ewes from 11 half-sib sire families were included in the study. The ewes were scored for the 5 linear traits used in the breeding scheme of the Churra breed to assess body conformation: stature, rear legs-rear view, foot angle, rump width, and general appearance. All the animals, including the 11 sires, were genotyped for 181 microsatellite markers evenly distributed across the 26 sheep autosomes. Using the yield deviations of the raw scores adjusted for fixed factors as phenotypic measurements, a quantitative trait loci (QTL) analysis was performed on the basis of a multi-marker regression method. Seven suggestive QTL were identified on chromosomes Ovis aries (OAR)2, OAR5, OAR16, OAR23, and OAR26, but none reached a genome-wise significance level. Putative QTL were identified for all of the traits analyzed, except for general appearance score. The suggestive QTL showing the highest test statistic influenced rear legs-rear view and was localized on OAR16, close to the growth hormone receptor coding gene, GHR. Some of the putative linkage associations reported here are consistent with previously reported QTL in cattle for similar traits. To the best of our knowledge, this study provides the first report of QTL for body conformation traits in dairy sheep; further studies will be needed to confirm and redefine the linkage associations reported herein. It is expected that future genome-wide association analyses of larger families will help identify genes underlying these putative genetic effects and provide useful markers for marker-assisted selection of such functional traits.

  7. Scanning the landscape of genome architecture of non-O1 and non-O139 Vibrio cholerae by whole genome mapping reveals extensive population genetic diversity.

    Directory of Open Access Journals (Sweden)

    Carol Chapman

    Full Text Available Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

  8. Scanning the landscape of genome architecture of non-O1 and non-O139 Vibrio cholerae by whole genome mapping reveals extensive population genetic diversity.

    Science.gov (United States)

    Chapman, Carol; Henry, Matthew; Bishop-Lilly, Kimberly A; Awosika, Joy; Briska, Adam; Ptashkin, Ryan N; Wagner, Trevor; Rajanna, Chythanya; Tsang, Hsinyi; Johnson, Shannon L; Mokashi, Vishwesh P; Chain, Patrick S G; Sozhamannan, Shanmuga

    2015-01-01

    Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping) based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

  9. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    Directory of Open Access Journals (Sweden)

    Abigail Bigham

    2010-09-01

    Full Text Available High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2, shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association

  10. Detection of quantitative trait loci affecting haematological traits in swine via genome scanning

    Directory of Open Access Journals (Sweden)

    Niu Xiao-Yan

    2010-06-01

    Full Text Available Abstract Background Haematological traits, which consist of mainly three components: leukocyte traits, erythrocyte traits and platelet traits, play extremely important role in animal immune function and disease resistance. But knowledge of the genetic background controlling variability of these traits is very limited, especially in swine. Results In the present study, 18 haematological traits (7 leukocyte traits, 7 erythrocyte traits and 4 platelet traits were measured in a pig resource population consisting of 368 purebred piglets of three breeds (Landrace, Large White and Songliao Black Pig, after inoculation with the swine fever vaccine when the pigs were 21 days old. A whole-genome scan of QTL for these traits was performed using 206 microsatellite markers covering all 18 autosomes and the X chromosome. Using variance component analysis based on a linear mixed model and the false discovery rate (FDR test, 35 QTL with FDR FDR FDR Conclusions Very few QTL were previously identified for hematological traits of pigs and never in purebred populations. Most of the QTL detected here, in particular the QTL for the platelet traits, have not been reported before. Our results lay important foundation for identifying the causal genes underlying the hematological trait variations in pigs.

  11. Allergic rhinitis - a total genome-scan for susceptibility genes suggests a locus on chromosome 4q24-q27

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schøitz, P O

    2001-01-01

    of allergic rhinitis on the contrary have as yet been most sparse. To identify candidate regions holding genes for allergic rhinitis we performed a total genome-scan on affected sib-pair families. From 100 Danish sib-pair families selected for allergy, families containing sib-pairs matching a phenotype...... definition of both clinical allergic rhinitis and confirmed specific allergy were chosen. Thirty-three affected sib-pair families qualified for the scan that was undertaken using 446 microsatellite markers. Non-parametric linkage results were obtained from MAPMAKER/SIBS computer program. The study revealed...

  12. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program.

    Science.gov (United States)

    Moore, Allan F; Jablonski, Kathleen A; McAteer, Jarred B; Saxena, Richa; Pollin, Toni I; Franks, Paul W; Hanson, Robert L; Shuldiner, Alan R; Knowler, William C; Altshuler, David; Florez, Jose C

    2008-09-01

    Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo. We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year. None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported ethnicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in beta-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05). We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B.

  13. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.

    Science.gov (United States)

    Norman, R A; Tataranni, P A; Pratley, R; Thompson, D B; Hanson, R L; Prochazka, M; Baier, L; Ehm, M G; Sakul, H; Foroud, T; Garvey, W T; Burns, D; Knowler, W C; Bennett, P H; Bogardus, C; Ravussin, E

    1998-01-01

    An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2. PMID:9497255

  14. A genome scan for QTL affecting resistance to Haemonchus contortus in sheep.

    Science.gov (United States)

    Sallé, G; Jacquiet, P; Gruner, L; Cortet, J; Sauvé, C; Prévot, F; Grisez, C; Bergeaud, J P; Schibler, L; Tircazes, A; François, D; Pery, C; Bouvier, F; Thouly, J C; Brunel, J C; Legarra, A; Elsen, J M; Bouix, J; Rupp, R; Moreno, C R

    2012-12-01

    Gastrointestinal nematodes are one of the main health issues in sheep breeding. To identify loci affecting the resistance to Haemonchus contortus, a genome scan was carried out using 1,275 Romane × Martinik Black Belly backcross lambs. The entire population was challenged with Haemonchus contortus in 2 consecutive experimental infections, and fecal egg counts (FEC) and packed cell volumes were measured. A subgroup of 332 lambs with extreme FEC was necropsied to determine the total worm burden, length of female worms, sex ratio in the worm population, abomasal pH, and serum and mucosal G immunoglobulins (IgG) responses. Pepsinogen concentration was measured in another subset of 229 lambs. For QTL detection, 160 microsatellite markers were used as well as the Illumina OvineSNP50 BeadChip that provided 42,469 SNP markers after quality control. Linkage, association, and joint linkage and association analyses were performed with the QTLMAP software. Linkage disequilibrium (LD) was estimated within each pure breed, and association analyses were carried out either considering or not the breed origin of the haplotypes. Four QTL regions on sheep chromosomes (OAR)5, 12, 13, and 21 were identified as key players among many other QTL with small to moderate effects. A QTL on OAR21 affecting pepsinogen concentration exactly matched the pepsinogen (PGA5) locus. A 10-Mbp region affecting FEC after the 1st and 2nd infections was found on OAR12. The SNP markers outperformed microsatellites in the linkage analysis. Taking advantage of the LD helped to refine the locations of the QTL mapped on OAR5 and 13.

  15. Genome-wide linkage scan for the metabolic syndrome: the GENNID study.

    Science.gov (United States)

    Edwards, Karen L; Hutter, Carolyn M; Wan, Jia Yin; Kim, Helen; Monks, Stephanie A

    2008-07-01

    In the United States, the metabolic syndrome (MetS) constitutes a major public health problem with over 47 million persons meeting clinical criteria for MetS. Numerous studies have suggested genetic susceptibility to MetS. The goals of this study were (i) to identify susceptibility loci for MetS in well-characterized families with type 2 diabetes (T2D) in four ethnic groups and (ii) to determine whether evidence for linkage varies across the four groups. The GENNID study (Genetics of NIDDM) is a multicenter study established by the American Diabetes Association in 1993 and comprises a comprehensive, well-characterized resource of T2D families from four ethnic groups (whites, Mexican Americans, African Americans, and Japanese Americans). Principal component factor analysis (PCFA) was used to define quantitative phenotypes of the MetS. Variance components linkage analysis was conducted using microsatellite markers from a 10-cM genome-wide linkage scan, separately in each of the four ethnic groups. Three quantitative MetS factors were identified by PCFA and used as phenotypes for MetS: (i) a weight/waist factor, (ii) a blood pressure factor, and (iii) a lipid factor. Evidence for linkage to each of these factors was observed. For each ethnic group, our results suggest that several regions harbor susceptibility genes for the MetS. The strongest evidence for linkage for MetS phenotypes was observed on chromosome 2 (2q12.1-2q13) in the white sample and on chromosome 3 (3q26.1-3q29) in the Mexican-American sample. In conclusion, the results suggest that several regions harbor MetS susceptibility genes and that heterogeneity may exist across groups.

  16. Beyond an AFLP genome scan towards the identification of immune genes involved in plague resistance in Rattus rattus from Madagascar.

    Science.gov (United States)

    Tollenaere, C; Jacquet, S; Ivanova, S; Loiseau, A; Duplantier, J-M; Streiff, R; Brouat, C

    2013-01-01

    Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague-mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague-mediated selection. © 2012 Blackwell Publishing Ltd.

  17. Cross-laboratory validation of the OncoScan® FFPE Assay, a multiplex tool for whole genome tumour profiling

    OpenAIRE

    Foster, Joseph M.; Oumie, Assa; Togneri, Fiona S; Vasques, Fabiana Ramos; Hau, Debra; Taylor, Morag; Tinkler-Hundal, Emma; Southward, Katie; Medlow, Paul; McGreeghan-Crosby, Keith; Halfpenny, Iris; McMullan, Dominic J.; Quirke, Phil; Keating, Katherine E; Griffiths, Mike

    2015-01-01

    Background Adoption of new technology in both basic research and clinical settings requires rigorous validation of analytical performance. The OncoScan® FFPE Assay is a multiplexing tool that offers genome-wide copy number and loss of heterozygosity detection, as well as identification of frequently tested somatic mutations. Methods In this study, 162 formalin fixed paraffin embedded samples, representing six different tumour types, were profiled in triplicate across three independent laborat...

  18. The relative power of genome scans to detect local adaptation depends on sampling design and statistical method.

    Science.gov (United States)

    Lotterhos, Katie E; Whitlock, Michael C

    2015-03-01

    Although genome scans have become a popular approach towards understanding the genetic basis of local adaptation, the field still does not have a firm grasp on how sampling design and demographic history affect the performance of genome scans on complex landscapes. To explore these issues, we compared 20 different sampling designs in equilibrium (i.e. island model and isolation by distance) and nonequilibrium (i.e. range expansion from one or two refugia) demographic histories in spatially heterogeneous environments. We simulated spatially complex landscapes, which allowed us to exploit local maxima and minima in the environment in 'pair' and 'transect' sampling strategies. We compared F(ST) outlier and genetic-environment association (GEA) methods for each of two approaches that control for population structure: with a covariance matrix or with latent factors. We show that while the relative power of two methods in the same category (F(ST) or GEA) depended largely on the number of individuals sampled, overall GEA tests had higher power in the island model and F(ST) had higher power under isolation by distance. In the refugia models, however, these methods varied in their power to detect local adaptation at weakly selected loci. At weakly selected loci, paired sampling designs had equal or higher power than transect or random designs to detect local adaptation. Our results can inform sampling designs for studies of local adaptation and have important implications for the interpretation of genome scans based on landscape data. © 2015 John Wiley & Sons Ltd.

  19. A scan statistic to extract causal gene clusters from case-control genome-wide rare CNV data

    Directory of Open Access Journals (Sweden)

    Scherer Stephen W

    2011-05-01

    Full Text Available Abstract Background Several statistical tests have been developed for analyzing genome-wide association data by incorporating gene pathway information in terms of gene sets. Using these methods, hundreds of gene sets are typically tested, and the tested gene sets often overlap. This overlapping greatly increases the probability of generating false positives, and the results obtained are difficult to interpret, particularly when many gene sets show statistical significance. Results We propose a flexible statistical framework to circumvent these problems. Inspired by spatial scan statistics for detecting clustering of disease occurrence in the field of epidemiology, we developed a scan statistic to extract disease-associated gene clusters from a whole gene pathway. Extracting one or a few significant gene clusters from a global pathway limits the overall false positive probability, which results in increased statistical power, and facilitates the interpretation of test results. In the present study, we applied our method to genome-wide association data for rare copy-number variations, which have been strongly implicated in common diseases. Application of our method to a simulated dataset demonstrated the high accuracy of this method in detecting disease-associated gene clusters in a whole gene pathway. Conclusions The scan statistic approach proposed here shows a high level of accuracy in detecting gene clusters in a whole gene pathway. This study has provided a sound statistical framework for analyzing genome-wide rare CNV data by incorporating topological information on the gene pathway.

  20. Candidate genes revealed by a genome scan for mosquito resistance to a bacterial insecticide: sequence and gene expression variations

    Directory of Open Access Journals (Sweden)

    David Jean-Philippe

    2009-11-01

    Full Text Available Abstract Background Genome scans are becoming an increasingly popular approach to study the genetic basis of adaptation and speciation, but on their own, they are often helpless at identifying the specific gene(s or mutation(s targeted by selection. This shortcoming is hopefully bound to disappear in the near future, thanks to the wealth of new genomic resources that are currently being developed for many species. In this article, we provide a foretaste of this exciting new era by conducting a genome scan in the mosquito Aedes aegypti with the aim to look for candidate genes involved in resistance to Bacillus thuringiensis subsp. israelensis (Bti insecticidal toxins. Results The genome of a Bti-resistant and a Bti-susceptible strains was surveyed using about 500 MITE-based molecular markers, and the loci showing the highest inter-strain genetic differentiation were sequenced and mapped on the Aedes aegypti genome sequence. Several good candidate genes for Bti-resistance were identified in the vicinity of these highly differentiated markers. Two of them, coding for a cadherin and a leucine aminopeptidase, were further examined at the sequence and gene expression levels. In the resistant strain, the cadherin gene displayed patterns of nucleotide polymorphisms consistent with the action of positive selection (e.g. an excess of high compared to intermediate frequency mutations, as well as a significant under-expression compared to the susceptible strain. Conclusion Both sequence and gene expression analyses agree to suggest a role for positive selection in the evolution of this cadherin gene in the resistant strain. However, it is unlikely that resistance to Bti is conferred by this gene alone, and further investigation will be needed to characterize other genes significantly associated with Bti resistance in Ae. aegypti. Beyond these results, this article illustrates how genome scans can build on the body of new genomic information (here, full

  1. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.

    Science.gov (United States)

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Gonzalez-José, Rolando; Headon, Denis; López-Otín, Carlos; Tobin, Desmond J; Balding, David; Ruiz-Linares, Andrés

    2016-03-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

  2. Family-Based Genome-Wide Association Scan of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Mick, Eric; Todorov, Alexandre; Smalley, Susan; Hu, Xiaolan; Loo, Sandra; Todd, Richard D.; Biederman, Joseph; Byrne, Deirdre; Dechairo, Bryan; Guiney, Allan; McCracken, James; McGough, James; Nelson, Stanley F.; Reiersen, Angela M.; Wilens, Timothy E.; Wozniak, Janet; Neale, Benjamin M.; Faraone, Stephen V.

    2010-01-01

    Objective: Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of…

  3. An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error

    DEFF Research Database (Denmark)

    Abbott, Diana; Li, Yi-Ju; Guggenheim, Jeremy A;

    2012-01-01

    To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites.......To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites....

  4. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Science.gov (United States)

    Gao, Hanxiang; Li, Lin; Rao, Shaoqi; Shen, Gongqing; Xi, Quansheng; Chen, Shenghan; Zhang, Zheng; Wang, Kai; Ellis, Stephen G; Chen, Qiuyun; Topol, Eric J; Wang, Qing K

    2014-01-01

    Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  5. Whole genome PCR scanning reveals the syntenic genome structure of toxigenic Vibrio cholerae strains in the O1/O139 population.

    Directory of Open Access Journals (Sweden)

    Bo Pang

    Full Text Available Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+ strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes.

  6. Genome scans for divergent selection in natural populations of the widespread hardwood species Eucalyptus grandis (Myrtaceae) using microsatellites

    Science.gov (United States)

    Song, Zhijiao; Zhang, Miaomiao; Li, Fagen; Weng, Qijie; Zhou, Chanpin; Li, Mei; Li, Jie; Huang, Huanhua; Mo, Xiaoyong; Gan, Siming

    2016-01-01

    Identification of loci or genes under natural selection is important for both understanding the genetic basis of local adaptation and practical applications, and genome scans provide a powerful means for such identification purposes. In this study, genome-wide simple sequence repeats markers (SSRs) were used to scan for molecular footprints of divergent selection in Eucalyptus grandis, a hardwood species occurring widely in costal areas from 32° S to 16° S in Australia. High population diversity levels and weak population structure were detected with putatively neutral genomic SSRs. Using three FST outlier detection methods, a total of 58 outlying SSRs were collectively identified as loci under divergent selection against three non-correlated climatic variables, namely, mean annual temperature, isothermality and annual precipitation. Using a spatial analysis method, nine significant associations were revealed between FST outlier allele frequencies and climatic variables, involving seven alleles from five SSR loci. Of the five significant SSRs, two (EUCeSSR1044 and Embra394) contained alleles of putative genes with known functional importance for response to climatic factors. Our study presents critical information on the population diversity and structure of the important woody species E. grandis and provides insight into the adaptive responses of perennial trees to climatic variations. PMID:27748400

  7. A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL

    Directory of Open Access Journals (Sweden)

    Bidanel Jean P

    2009-12-01

    Full Text Available Abstract Background Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA and total number of piglets born (TNB in a three generation Iberian by Meishan F2 intercross. Results The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P SSC17 (P P P P P Conclusions The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17, dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.

  8. Incremental diagnostic quality gain of CTA over V/Q scan in the assessment of pulmonary embolism by means of a Wells score Bayesian model: results from the ACDC collaboration.

    Science.gov (United States)

    Cochon, Laila; McIntyre, Kaitlin; Nicolás, José M; Baez, Amado Alejandro

    2017-08-01

    Our objective was to evaluate the diagnostic value of computed tomography angiography (CTA) and ventilation perfusion (V/Q) scan in the assessment of pulmonary embolism (PE) by means of a Bayesian statistical model. Wells criteria defined pretest probability. Sensitivity and specificity of CTA and V/Q scan for PE were derived from pooled meta-analysis data. Likelihood ratios calculated for CTA and V/Q were inserted in the nomogram. Absolute (ADG) and relative diagnostic gains (RDG) were analyzed comparing post- and pretest probability. Comparative gain difference was calculated for CTA ADG over V/Q scan integrating ANOVA p value set at 0.05. The sensitivity for CT was 86.0% (95% CI: 80.2%, 92.1%) and specificity of 93.7% (95% CI: 91.1%, 96.3%). The V/Q scan yielded a sensitivity of 96% (95% CI: 95%, 97%) and a specificity of 97% (95% CI: 96%, 98%). Bayes nomogram results for CTA were low risk and yielded a posttest probability of 71.1%, an ADG of 56.1%, and an RDG of 374%, moderate-risk posttest probability was 85.1%, an ADG of 56.1%, and an RDG of 193.4%, and high-risk posttest probability was 95.2%, an ADG of 36.2%, and an RDG of 61.35%. The comparative gain difference for low-risk population was 46.1%; in moderate-risk 41.6%; and in high-risk a 22.1% superiority. ANOVA analysis for LR+ and LR- showed no significant difference (p = 0.8745, p = 0.9841 respectively). This Bayesian model demonstrated a superiority of CTA when compared to V/Q scan for the diagnosis of pulmonary embolism. Low-risk patients are recognized to have a superior overall comparative gain favoring CTA.

  9. ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling | Office of Cancer Genomics

    Science.gov (United States)

    Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives.

  10. The Application of Restriction Landmark Genome Scanning Method for Surveillance of Non-Mendelian Inheritance in F1 Hybrids

    Directory of Open Access Journals (Sweden)

    Tomoko Takamiya

    2009-01-01

    Full Text Available We analyzed inheritance of DNA methylation in reciprocal F1 hybrids (subsp. japonica cv. Nipponbare × subsp. indica cv. Kasalath of rice (Oryza sativa L. using restriction landmark genome scanning (RLGS, and detected differing RLGS spots between the parents and reciprocal F1 hybrids. MspI/HpaII restriction sites in the DNA from these different spots were suspected to be heterozygously methylated in the Nipponbare parent. These spots segregated in F1 plants, but did not segregate in selfed progeny of Nipponbare, showing non-Mendelian inheritance of the methylation status. As a result of RT-PCR and sequencing, a specific allele of the gene nearest to the methylated sites was expressed in reciprocal F1 plants, showing evidence of biased allelic expression. These results show the applicability of RLGS for scanning of non-Mendelian inheritance of DNA methylation and biased allelic expression.

  11. Scanning for genes in large genomic regions: cosmid-based exon trapping of multiple exons in a single product.

    OpenAIRE

    Datson, N.A.; Vosse, E van de; Dauwerse, H.G.; Bout, M; van Ommen, G J; J T den Dunnen

    1996-01-01

    To facilitate the scanning of large genomic regions for the presence of exonic gene segments we have constructed a cosmid-based exon trap vector. The vector serves a dual purpose since it is also suitable for contig construction and physical mapping. The exon trap cassette of vector sCOGH1 consists of the human growth hormone gene driven by the mouse mettallothionein-1 promoter. Inserts are cloned in the multicloning site located in intron 2 of the hGH gene. The efficiency of the system is de...

  12. Whole-Genome Scans Provide Evidence of Adaptive Evolution in Malawian Plasmodium falciparum Isolates

    DEFF Research Database (Denmark)

    Ocholla, Harold; Preston, Mark D; Mipando, Mwapatsa

    2014-01-01

    BACKGROUND:  Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation. METHODS:  We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used ...

  13. A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women

    Science.gov (United States)

    Song, Chi; Chen, Gary K.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Chanock, Stephen J.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Chris A.; Stram, Daniel O.

    2013-01-01

    Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. PMID:23468962

  14. A large genome scan for rare CNVs in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Blauw, H.M.; Al-Chalabi, A.; Andersen, P.M.; Vught, P.W. van; Diekstra, F.P.; Es, M.A. van; Saris, C.G.J.; Groen, E.J.; Rheenen, W. van; Koppers, M.; Slot, R. van 't; Strengman, E.; Estrada, K.; Rivadeneira, F.; Hofman, A.; Uitterlinden, A.G.; Kiemeney, L.A.L.M.; Vermeulen, H.H.M.; Birve, A.; Waibel, S.; Meyer, T.; Cronin, S.; McLaughlin, R.L.; Hardiman, O.; Sapp, P.C.; Tobin, M.D.; Wain, L.V.; Tomik, B.; Slowik, A.; Lemmens, R.; Rujescu, D.; Schulte, C.; Gasser, T.; Brown Jr., R.H.; Landers, J.E.; Robberecht, W.; Ludolph, A.C.; Ophoff, R.A.; Veldink, J.H.; Berg, L.H. van den

    2010-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number

  15. A genome-wide scan for common alleles affecting risk for autism

    NARCIS (Netherlands)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Boelte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; osey, David J.; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Ines; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-01-01

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD fa

  16. A genome-wide scan for common alleles affecting risk for autism

    NARCIS (Netherlands)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Boelte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; osey, David J.; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Ines; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-01-01

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD fa

  17. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evid

  18. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  19. Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan

    Science.gov (United States)

    Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be easily seen by analyzing the unexpected behaviour of the linkage disequilibrium (LD) decay. A heuristic process was proposed to identify those misassembly signatures and presented the ones found in ...

  20. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Directory of Open Access Journals (Sweden)

    Hanxiang Gao

    Full Text Available Coronary artery disease (CAD is the leading cause of death worldwide. Recent genome-wide association studies (GWAS identified >50 common variants associated with CAD or its complication myocardial infarction (MI, but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49 and 3q29 (NPL  = 6.84. We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07. These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  1. Identification of outliers in a genomic scan for selection along environmental gradients in the bamboo locust, Ceracris kiangsu.

    Science.gov (United States)

    Feng, Xiao-Jing; Jiang, Guo-Fang; Fan, Zhou

    2015-09-03

    Identification of loci under divergent selection is a key step in understanding the evolutionary process because those loci are responsible for the genetic variations that affect fitness in different environments. Understanding how environmental forces give rise to adaptive genetic variation is a challenge in pest control. Here, we performed an amplified fragment length polymorphism (AFLP) genome scan in populations of the bamboo locust, Ceracris kiangsu, to search for candidate loci that are influenced by selection along an environmental gradient in southern China. In outlier locus detection, loci that demonstrate significantly higher or lower among-population genetic differentiation than expected under neutrality are identified as outliers. We used several outlier detection methods to study the features of C. kiangsu, including method DFDIST, BayeScan, and logistic regression. A total of 97 outlier loci were detected in the C. kiangsu genome with very high statistical supports. Moreover, the results suggested that divergent selection arising from environmental variation has been driven by differences in temperature, precipitation, humidity and sunshine. These findings illustrate that divergent selection and potential local adaptation are prevalent in locusts despite seemingly high levels of gene flow. Thus, we propose that native environments in each population may induce divergent natural selection.

  2. Efficient Haplotype Inference Algorithms in One Whole Genome Scan for Pedigree Data with Non-genotyped Founders

    Institute of Scientific and Technical Information of China (English)

    Yongxi Cheng; Hadi Sabaa; Zhipeng Cai; Randy Goebel; Guohui Lin

    2009-01-01

    An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases where some pedigree founders are not genotyped, provided that for each nuclear family at least one parent is genotyped and each non-genotyped founder appears in exactly one nuclear family. The importance of this generalization lies in that such cases frequently happen in real data, because some founders may have passed away and their genotype data can no longer be collected. The algorithm runs in O(m3n3) time, where m is the number of single nucleotide polymorphism (SNP) loci under consideration and n is the number of genotyped members in the pedigree. This zero-recombination haplotyping algorithm is extended to a maximum parsimoniously haplotyping algorithm in one whole genome scan to minimize the total number of breakpoint sites, or equivalently, the number of maximal zero-recombination chromosomal regions. We show that such a whole genome scan haplotyping algorithm can be implemented in O(m3n3) time in a novel incremental fashion,here m denotes the total number of SNP loci along the chromosome.

  3. A 2cM genome-wide scan of European Holstein cattle affected by classical BSE

    Directory of Open Access Journals (Sweden)

    Prasad Aparna

    2010-03-01

    Full Text Available Abstract Background Classical bovine spongiform encephalopathy (BSE is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with variations in transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism (SNP markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic. Results Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set of paired cases with controls. The family set comprises half-sibling progeny from six sires. The progeny from four of these sires had previously been scanned with microsatellite markers. The results obtained from the current analysis of the family set yielded both some supporting and new results compared with those obtained in the earlier study. The results revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease. These results confirm a region previously reported on chromosome 20, and identify additional regions on chromosomes 2, 14, 16, 21 and 28. This study did not identify a significant association near the PRNP in the family sample set. The only association found in the PRNP

  4. A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bustamente, Carlos; Clark, Andrew G.

    2005-01-01

    of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome...... such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved...... in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some...

  5. Multiple type 2 diabetes susceptibility genes following genome-wide association scan in UK samples

    OpenAIRE

    Zeggini, Eleftheria; Michael N. Weedon; Lindgren, Cecilia M.; Frayling, Timothy M; Elliott, Katherine S.; Lango, Hana; Nicholas J Timpson; Perry, John R B; Nigel W Rayner; Freathy, Rachel M; Barrett, Jeffrey C.; Shields, Beverley; Andrew P Morris; Ellard, Sian; Groves, Christopher J

    2007-01-01

    The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1,924 diabetic cases and 2,938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3,757 additional cases and 5,346 controls, and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibilit...

  6. A genome-wide scan for selection signatures in Nellore cattle.

    Science.gov (United States)

    Somavilla, A L; Sonstegard, T S; Higa, R H; Rosa, A N; Siqueira, F; Silva, L O C; Torres Júnior, R A A; Coutinho, L L; Mudadu, M A; Alencar, M M; Regitano, L C A

    2014-12-01

    Brazilian Nellore cattle (Bos indicus) have been selected for growth traits for over more than four decades. In recent years, reproductive and meat quality traits have become more important because of increasing consumption, exports and consumer demand. The identification of genome regions altered by artificial selection can potentially permit a better understanding of the biology of specific phenotypes that are useful for the development of tools designed to increase selection efficiency. Therefore, the aims of this study were to detect evidence of recent selection signatures in Nellore cattle using extended haplotype homozygosity methodology and BovineHD marker genotypes (>777,000 single nucleotide polymorphisms) as well as to identify corresponding genes underlying these signals. Thirty-one significant regions (P meat quality, fatty acid profiles and immunity. In addition, 545 genes were identified in regions harboring selection signatures. Within this group, 58 genes were associated with growth, muscle and adipose tissue metabolism, reproductive traits or the immune system. Using relative extended haplotype homozygosity to analyze high-density single nucleotide polymorphism marker data allowed for the identification of regions potentially under artificial selection pressure in the Nellore genome, which might be used to better understand autozygosity and the effects of selection on the Nellore genome.

  7. Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever.

    Science.gov (United States)

    Andersen, Kristian G; Shylakhter, Ilya; Tabrizi, Shervin; Grossman, Sharon R; Happi, Christian T; Sabeti, Pardis C

    2012-03-19

    Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 (IL21), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21. Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit.

  8. The difficulty of avoiding false positives in genome scans for natural selection.

    Science.gov (United States)

    Mallick, Swapan; Gnerre, Sante; Muller, Paul; Reich, David

    2009-05-01

    Several studies have found evidence for more positive selection on the chimpanzee lineage compared with the human lineage since the two species split. A potential concern, however, is that these findings may simply reflect artifacts of the data: inaccuracies in the underlying chimpanzee genome sequence, which is of lower quality than human. To test this hypothesis, we generated de novo genome assemblies of chimpanzee and macaque and aligned them with human. We also implemented a novel bioinformatic procedure for producing alignments of closely related species that uses synteny information to remove misassembled and misaligned regions, and sequence quality scores to remove nucleotides that are less reliable. We applied this procedure to re-examine 59 genes recently identified as candidates for positive selection in chimpanzees. The great majority of these signals disappear after application of our new bioinformatic procedure. We also carried out laboratory-based resequencing of 10 of the regions in multiple chimpanzees and humans, and found that our alignments were correct wherever there was a conflict with the published results. These findings throw into question previous findings that there has been more positive selection in chimpanzees than in humans since the two species diverged. Our study also highlights the challenges of searching the extreme tails of distributions for signals of natural selection. Inaccuracies in the genome sequence at even a tiny fraction of genes can produce false-positive signals, which make it difficult to identify loci that have genuinely been targets of selection.

  9. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Alfred Amambua-Ngwa

    Full Text Available Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3, and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%, indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing

  10. Bayesian biostatistics

    CERN Document Server

    Lesaffre, Emmanuel

    2012-01-01

    The growth of biostatistics has been phenomenal in recent years and has been marked by considerable technical innovation in both methodology and computational practicality. One area that has experienced significant growth is Bayesian methods. The growing use of Bayesian methodology has taken place partly due to an increasing number of practitioners valuing the Bayesian paradigm as matching that of scientific discovery. In addition, computational advances have allowed for more complex models to be fitted routinely to realistic data sets. Through examples, exercises and a combination of introd

  11. Quantitative linkage genome scan for atopy in a large collection of Caucasian families

    DEFF Research Database (Denmark)

    Webb, BT; van den Oord, E; Akkari, A

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early...... adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma...

  12. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    OpenAIRE

    Lindgren, Cecilia; Heid, Iris; Randall, Joshua; Lamina, Claudia; Steinthorsdottir, Valgerdur; Qi, Lu; Speliotes, Elizabeth; Thorleifsson, Gudmar; Willer, Cristen; Herrera, Blanca; Jackson, Anne; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals ...

  13. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    OpenAIRE

    Lindgren, Cecilia M; Heid, Iris M.; Randall, Joshua C.; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Speliotes, Elizabeth K.; Gudmar Thorleifsson; Willer, Cristen J.; Herrera, Blanca M; Jackson, Anne U.; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin

    2009-01-01

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified t...

  14. The prevalences of Salmonella Genomic Island 1 variants in human and animal Salmonella Typhimurium DT104 are distinguishable using a Bayesian approach.

    Directory of Open Access Journals (Sweden)

    Alison E Mather

    Full Text Available Throughout the 1990 s, there was an epidemic of multidrug resistant Salmonella Typhimurium DT104 in both animals and humans in Scotland. The use of antimicrobials in agriculture is often cited as a major source of antimicrobial resistance in pathogenic bacteria of humans, suggesting that DT104 in animals and humans should demonstrate similar prevalences of resistance determinants. Until very recently, only the application of molecular methods would allow such a comparison and our understanding has been hindered by the fact that surveillance data are primarily phenotypic in nature. Here, using large scale surveillance datasets and a novel Bayesian approach, we infer and compare the prevalence of Salmonella Genomic Island 1 (SGI1, SGI1 variants, and resistance determinants independent of SGI1 in animal and human DT104 isolates from such phenotypic data. We demonstrate differences in the prevalences of SGI1, SGI1-B, SGI1-C, absence of SGI1, and tetracycline resistance determinants independent of SGI1 between these human and animal populations, a finding that challenges established tenets that DT104 in domestic animals and humans are from the same well-mixed microbial population.

  15. A scan for positively selected genes in the genomes of humans and chimpanzees.

    Directory of Open Access Journals (Sweden)

    Rasmus Nielsen

    2005-06-01

    Full Text Available Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

  16. An evolutionary genome scan for longevity-related natural selection in mammals.

    Science.gov (United States)

    Jobson, Richard W; Nabholz, Benoit; Galtier, Nicolas

    2010-04-01

    Aging is thought to occur through the accumulation of biochemical damage affecting DNA, proteins, and lipids. The major source of cellular damage involves the generation of reactive oxygen species produced during mitochondrial respiratory activity of the electron transport chain. Energetic metabolism, antioxidative processes, genome maintenance, and cell cycle are the cellular functions most commonly associated with aging, from experimental studies of model organisms. The significance of these experiments with respect to longevity-related selective constraints in nature remains unclear. Here we took a phylogenomic approach to identify the genetic targets of natural selection for elongated life span in mammals. By comparing the nonsynonymous and synonymous evolution of approximately 5.7 million codon sites across 25 species, we identify codons and genes showing a stronger level of amino acid conservation in long-lived than in short-lived lineages. We show that genes involved in lipid composition and (collagen associated) vitamin C binding have collectively undergone increased selective pressure in long-lived species, whereas genes involved in DNA replication/repair or antioxidation have not. Most of the candidate genes experimentally associated with aging (e.g., PolG, Sod, Foxo) have played no detectable role in the evolution of longevity in mammals. A large body of current medical research aims at discovering how to increase longevity in human. In this study, we uncovered the way natural selection has completed this task during mammalian evolution. Cellular membrane and extracellular collagen composition, not genome integrity, have apparently been the optimized features.

  17. A genome-wide scan for common alleles affecting risk for autism

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-01-01

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. PMID:20663923

  18. A genome-wide scan for common alleles affecting risk for autism.

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Sykes, Nuala; Pagnamenta, Alistair T; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chu, Su H; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Melhem, Nadine M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Scherer, Stephen W; Sutcliffe, James S; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  19. Genome-wide association scan suggests basis for microtia in Awassi sheep.

    Science.gov (United States)

    Jawasreh, K; Boettcher, P J; Stella, A

    2016-08-01

    Hereditary underdevelopment of the ear, a condition also known as microtia, has been observed in several sheep breeds as well as in humans and other species. Its genetic basis in sheep is unknown. The Awassi sheep, a breed native to southwest Asia, carries this phenotype and was targeted for molecular characterization via a genome-wide association study. DNA samples were collected from sheep in Jordan. Eight affected and 12 normal individuals were genotyped with the Illumina OvineSNP50(®) chip. Multilocus analyses failed to identify any genotypic association. In contrast, a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago. Many of the earless sheep breeds may thus share the causative mutation, especially within the subgroup of fat-tailed, wool sheep.

  20. A genome-wide scan for common alleles affecting risk for autism.

    LENUS (Irish Health Repository)

    Anney, Richard

    2010-10-15

    Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner\\'s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

  1. Bayesian statistics

    OpenAIRE

    新家, 健精

    2013-01-01

    © 2012 Springer Science+Business Media, LLC. All rights reserved. Article Outline: Glossary Definition of the Subject and Introduction The Bayesian Statistical Paradigm Three Examples Comparison with the Frequentist Statistical Paradigm Future Directions Bibliography

  2. Identifying genomic regions for fine-mapping using genome scan meta-analysis (GSMA to identify the minimum regions of maximum significance (MRMS across populations

    Directory of Open Access Journals (Sweden)

    Maher Brion S

    2005-12-01

    Full Text Available Abstract In order to detect linkage of the simulated complex disease Kofendrerd Personality Disorder across studies from multiple populations, we performed a genome scan meta-analysis (GSMA. Using the 7-cM microsatellite map, nonparametric multipoint linkage analyses were performed separately on each of the four simulated populations independently to determine p-values. The genome of each population was divided into 20-cM bin regions, and each bin was rank-ordered based on the most significant linkage p-value for that population in that region. The bin ranks were then averaged across all four studies to determine the most significant 20-cM regions over all studies. Statistical significance of the averaged bin ranks was determined from a normal distribution of randomly assigned rank averages. To narrow the region of interest for fine-mapping, the meta-analysis was repeated two additional times, with each of the 20-cM bins offset by 7 cM and 13 cM, respectively, creating regions of overlap with the original method. The 6–7 cM shared regions, where the highest averaged 20-cM bins from each of the three offsets overlap, designated the minimum region of maximum significance (MRMS. Application of the GSMA-MRMS method revealed genome wide significance (p-values refer to the average rank assigned to the bin at regions including or adjacent to all of the simulated disease loci: chromosome 1 (p p-value p-value p-value

  3. Identifying genomic regions for fine-mapping using genome scan meta-analysis (GSMA) to identify the minimum regions of maximum significance (MRMS) across populations.

    Science.gov (United States)

    Cooper, Margaret E; Goldstein, Toby H; Maher, Brion S; Marazita, Mary L

    2005-12-30

    In order to detect linkage of the simulated complex disease Kofendrerd Personality Disorder across studies from multiple populations, we performed a genome scan meta-analysis (GSMA). Using the 7-cM microsatellite map, nonparametric multipoint linkage analyses were performed separately on each of the four simulated populations independently to determine p-values. The genome of each population was divided into 20-cM bin regions, and each bin was rank-ordered based on the most significant linkage p-value for that population in that region. The bin ranks were then averaged across all four studies to determine the most significant 20-cM regions over all studies. Statistical significance of the averaged bin ranks was determined from a normal distribution of randomly assigned rank averages. To narrow the region of interest for fine-mapping, the meta-analysis was repeated two additional times, with each of the 20-cM bins offset by 7 cM and 13 cM, respectively, creating regions of overlap with the original method. The 6-7 cM shared regions, where the highest averaged 20-cM bins from each of the three offsets overlap, designated the minimum region of maximum significance (MRMS). Application of the GSMA-MRMS method revealed genome wide significance (p-values refer to the average rank assigned to the bin) at regions including or adjacent to all of the simulated disease loci: chromosome 1 (p value value value < 0.05 for 7-14 cM, the region adjacent to D4). This GSMA analysis approach demonstrates the power of linkage meta-analysis to detect multiple genes simultaneously for a complex disorder. The MRMS method enhances this powerful tool to focus on more localized regions of linkage.

  4. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  5. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  6. Genomic Scans of Zygotic Disequilibrium and Epistatic SNPs in HapMap Phase III Populations.

    Directory of Open Access Journals (Sweden)

    Xin-Sheng Hu

    Full Text Available Previous theory indicates that zygotic linkage disequilibrium (LD is more informative than gametic or composite digenic LD in revealing natural population history. Further, the difference between the composite digenic and maximum zygotic LDs can be used to detect epistatic selection for fitness. Here we corroborate the theory by investigating genome-wide zygotic LDs in HapMap phase III human populations. Results show that non-Africa populations have much more significant zygotic LDs than do Africa populations. Africa populations (ASW, LWK, MKK, and YRI possess more significant zygotic LDs for the double-homozygotes (DAABB than any other significant zygotic LDs (DAABb, DAaBB, and DAaBb, while non-Africa populations generally have more significant DAaBb's than any other significant zygotic LDs (DAABB, DAABb, and DAaBB. Average r-squares for any significant zygotic LDs increase generally in an order of populations YRI, MKK, CEU, CHB, LWK, JPT, CHD, TSI, GIH, ASW, and MEX. Average r-squares are greater for DAABB and DAaBb than for DAaBB and DAABb in each population. YRI and MKK can be separated from LWK and ASW in terms of the pattern of average r-squares. All population divergences in zygotic LDs can be interpreted with the model of Out of Africa for modern human origins. We have also detected 19735-95921 SNP pairs exhibiting strong signals of epistatic selection in different populations. Gene-gene interactions for some epistatic SNP pairs are evident from empirical findings, but many more epistatic SNP pairs await evidence. Common epistatic SNP pairs rarely exist among all populations, but exist in distinct regions (Africa, Europe, and East Asia, which helps to understand geographical genomic medicine.

  7. Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Caporaso, Neil; Casey, Graham; Deming, Sandra L.; Diver, W. Ryan; Gapstur, Susan M.; Gillanders, Elizabeth M.; Harris, Curtis C.; Henderson, Brian E.; Ingles, Sue A.; Isaacs, William; De Jager, Phillip L.; John, Esther M.; Kittles, Rick A.; Larkin, Emma; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Tucker, Margaret A.; Wiencke, John K.; Witte, John S.; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Chanock, Stephen J.; Haiman, Christopher A.; Reich, David; Price, Alkes L.

    2014-01-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. PMID:25242497

  8. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

    Science.gov (United States)

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Caporaso, Neil; Casey, Graham; Deming, Sandra L; Diver, W Ryan; Gapstur, Susan M; Gillanders, Elizabeth M; Harris, Curtis C; Henderson, Brian E; Ingles, Sue A; Isaacs, William; De Jager, Phillip L; John, Esther M; Kittles, Rick A; Larkin, Emma; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Tucker, Margaret A; Wiencke, John K; Witte, John S; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Chanock, Stephen J; Haiman, Christopher A; Reich, David; Price, Alkes L

    2014-10-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

  9. Genome scan for locus involved in mandibular prognathism in pedigrees from China.

    Directory of Open Access Journals (Sweden)

    Qin Li

    Full Text Available BACKGROUND: It is well known that genetic components play an important role in the etiology of mandibular prognathism, but few susceptibility loci have been mapped. METHODOLOGY: In order to identify linkage regions for mandibular prognathism, we analyzed two Chinese pedigrees with 6,090 genome-wide single-nucleotide polymorphism (SNP markers from Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM. Multipoint parametric and non-parametric (model-free linkage analyses were used for the pedigrees. PRINCIPAL FINDING: The most statistically significant linkage results were with markers on chromosome 4 (LOD=3.166 and NPL=3.65 with rs 875864, 4p16.1, 8.38 cM. Candidate genes within the 4p16.1 include EVC, EVC2. CONCLUSION: We detected a novel suggestive linkage locus for mandibular prognathism in two Chinese pedigrees, and this linkage region provides target for susceptibility gene identification, a process that will provide important insights into the molecular and cellular basis of mandibular prognathism.

  10. Univariate/multivariate genome-wide association scans using data from families and unrelated samples.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available As genome-wide association studies (GWAS are becoming more popular, two approaches, among others, could be considered in order to improve statistical power for identifying genes contributing subtle to moderate effects to human diseases. The first approach is to increase sample size, which could be achieved by combining both unrelated and familial subjects together. The second approach is to jointly analyze multiple correlated traits. In this study, by extending generalized estimating equations (GEEs, we propose a simple approach for performing univariate or multivariate association tests for the combined data of unrelated subjects and nuclear families. In particular, we correct for population stratification by integrating principal component analysis and transmission disequilibrium test strategies. The proposed method allows for multiple siblings as well as missing parental information. Simulation studies show that the proposed test has improved power compared to two popular methods, EIGENSTRAT and FBAT, by analyzing the combined data, while correcting for population stratification. In addition, joint analysis of bivariate traits has improved power over univariate analysis when pleiotropic effects are present. Application to the Genetic Analysis Workshop 16 (GAW16 data sets attests to the feasibility and applicability of the proposed method.

  11. A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

    Science.gov (United States)

    Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

    2015-01-01

    Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

  12. A genome scan for quantitative trait loci affecting the Salmonella carrier-state in the chicken

    Directory of Open Access Journals (Sweden)

    Bumstead Nat

    2005-09-01

    Full Text Available Abstract Selection for increased resistance to Salmonella colonisation and excretion could reduce the risk of foodborne Salmonella infection. In order to identify potential loci affecting resistance, differences in resistance were identified between the N and 61 inbred lines and two QTL research performed. In an F2 cross, the animals were inoculated at one week of age with Salmonella enteritidis and cloacal swabs were carried out 4 and 5 wk post inoculation (thereafter called CSW4F2 and CSW4F2 and caecal contamination (CAECF2 was assessed 1 week later. The animals from the (N × 61 × N backcross were inoculated at six weeks of age with Salmonella typhimurium and cloacal swabs were studied from wk 1 to 4 (thereafter called CSW1BC to CSW4BC. A total of 33 F2 and 46 backcross progeny were selectively genotyped for 103 and 135 microsatellite markers respectively. The analysis used least-squares-based and non-parametric interval mapping. Two genome-wise significant QTL were observed on Chromosome 1 for CSW2BC and on Chromosome 2 for CSW4F2, and four suggestive QTL for CSW5F2 on Chromosome 2, for CSW5F2 and CSW2BC on chromosome 5 and for CAECF2 on chromosome 16. These results suggest new regions of interest and the putative role of SAL1.

  13. Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans

    Directory of Open Access Journals (Sweden)

    Avinash M. Veerappa

    2016-01-01

    Full Text Available Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4% than in UGT2B15 (17.6%. Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases.

  14. A genome scan for candidate genes involved in the adaptation of turbot (Scophthalmus maximus).

    Science.gov (United States)

    Vilas, Román; Vandamme, Sara G; Vera, Manuel; Bouza, Carmen; Maes, Gregory E; Volckaert, Filip A M; Martínez, Paulino

    2015-10-01

    Partitioning phenotypic variance in genotypic and environmental variance may benefit from the population genomic assignment of genes putatively involved in adaptation. We analyzed a total of 256 markers (120 microsatellites and 136 Single Nucleotide Polymorphisms - SNPs), several of them associated to Quantitative Trait Loci (QTL) for growth and resistance to pathologies, with the aim to identify potential adaptive variation in turbot Scophthalmus maximus L. The study area in the Northeastern Atlantic Ocean, from Iberian Peninsula to the Baltic Sea, involves a gradual change in temperature and an abrupt change in salinity conditions. We detected 27 candidate loci putatively under selection. At least four of the five SNPs identified as outliers are located within genes coding for ribosomal proteins or directly related with the production of cellular proteins. One of the detected outliers, previously identified as part of a QTL for growth, is a microsatellite linked to a gene coding for a growth factor receptor. A similar set of outliers was detected when natural populations were compared with a sample subjected to strong artificial selection for growth along four generations. The observed association between FST outliers and growth-related QTL supports the hypothesis of changes in growth as an adaptation to differences in temperature and salinity conditions. However, further work is needed to confirm this hypothesis.

  15. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

    Science.gov (United States)

    Qi, Lu; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jian'an; Lyon, Helen N.; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Zhao, Jing Hua; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S. F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Hofman, Albert; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N. A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scott, Laura J.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Yuan, Xin; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C. M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Davey Smith, George; Day, Ian N. M.; Franks, Paul W.; Hattersley, Andrew T.; Hu, Frank B.; Jarvelin, Marjo-Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; van Duijn, Cornelia M.; Wareham, Nicholas J.; Watkins for the PROCARDIS consortia, Hugh; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Hunter, David J.; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H.-Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Hirschhorn, Joel N.; Loos, Ruth J. F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; McCarthy for the GIANT consortium, Mark I.

    2009-01-01

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×10−11) and MSRA (WC, P = 8.9×10−9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10−8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity. PMID:19557161

  16. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  17. A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study

    Science.gov (United States)

    Li, Jian-Liang; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R.; Durr, Alexandra; Dodé, Catherine; Morrison, Patrick J.; Suchowersky, Oksana; Ross, Christopher A.; Margolis, Russell L.; Rosenblatt, Adam; Gómez-Tortosa, Estrella; Cabrero, David Mayo; Novelletto, Andrea; Frontali, Marina; Nance, Martha; Trent, Ronald J. A.; McCusker, Elizabeth; Jones, Randi; Paulsen, Jane S.; Harrison, Madeline; Zanko, Andrea; Abramson, Ruth K.; Russ, Ana L.; Knowlton, Beth; Djoussé, Luc; Mysore, Jayalakshmi S.; Tariot, Suzanne; Gusella, Michael F.; Wheeler, Vanessa C.; Atwood, Larry D.; Cupples, L. Adrienne; Saint-Hilaire, Marie; Cha, Jang-Ho J.; Hersch, Steven M.; Koroshetz, Walter J.; Gusella, James F.; MacDonald, Marcy E.; Myers, Richard H.

    2003-01-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21–23 (LOD=2.29), and 6q24–26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD. PMID:12900792

  18. Bayesian Theory

    CERN Document Server

    Bernardo, Jose M

    2000-01-01

    This highly acclaimed text, now available in paperback, provides a thorough account of key concepts and theoretical results, with particular emphasis on viewing statistical inference as a special case of decision theory. Information-theoretic concepts play a central role in the development of the theory, which provides, in particular, a detailed discussion of the problem of specification of so-called prior ignorance . The work is written from the authors s committed Bayesian perspective, but an overview of non-Bayesian theories is also provided, and each chapter contains a wide-ranging critica

  19. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q.

    NARCIS (Netherlands)

    Bakker, S.C.; Meulen, E.M. van der; Sandkuijl, L.A.; Pauls, D.L.; Monsuur, A.J.; Slot, R. van 't; Minderaa, R.B.; Gunning, W.B.; Pearson, P.L.; Sinke, R.J.

    2003-01-01

    A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition. Initially

  20. A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder : Suggestive evidence for linkage on chromosomes 7p and 15q

    NARCIS (Netherlands)

    Bakker, SC; van der Meulen, EM; Buitelaar, JK; Sandkuijl, LA; Pauls, DL; Monsuur, AJ; van't Slot, R; Minderaa, RB; Gunning, WB; Pearson, PL; Sinke, RJ

    2003-01-01

    A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition. Initially

  1. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    Science.gov (United States)

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  2. Genome-wide scan for bovine milk-fat composition. I. Quantitative trait loci for short- and medium-chain fatty acids

    NARCIS (Netherlands)

    Stoop, W.M.; Schennink, A.; Visker, M.H.P.W.; Mullaart, E.; Arendonk, van J.A.M.; Bovenhuis, H.

    2009-01-01

    A genome-wide scan was performed to identify quantitative trait loci (QTL) for short- and medium-chain fatty acids (expressed in wt/wt %). Milk samples were available from 1,905 cows from 398 commercial herds in the Netherlands, and milk-fat composition was measured by gas chromatography. DNA was av

  3. Short communication: Genome-wide scan for bovine milk-fat composition. II. Quantitative trait loci for long-chain fatty acids

    NARCIS (Netherlands)

    Schennink, A.; Stoop, W.M.; Visker, M.H.P.W.; Poel, van der J.J.; Bovenhuis, H.; Arendonk, van J.A.M.

    2009-01-01

    We present the results of a genome-wide scan to identify quantitative trait loci (QTL) that contribute to genetic variation in long-chain milk fatty acids. Milk-fat composition phenotypes were available on 1,905 Dutch Holstein-Friesian cows. A total of 849 cows and their 7 sires were genotyped for 1

  4. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  5. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Yannick Allanore

    2011-07-01

    Full Text Available Systemic sclerosis (SSc is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10(-5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10(-8, OR = 0.69, 95% CI [0.60-0.79]; rs6457617, P = 1.14×10(-7 and rs9275245, P = 1.39×10(-7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10(-5, OR = 1.36 [1.18-1.56] is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10(-5 that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10(-10, OR:1.25, TNIP1 (P = 4.68×10(-9, OR:1.31, and RHOB loci (P = 3.17×10(-6, OR:1.21. Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of

  6. Bayesian SPLDA

    OpenAIRE

    Villalba, Jesús

    2015-01-01

    In this document we are going to derive the equations needed to implement a Variational Bayes estimation of the parameters of the simplified probabilistic linear discriminant analysis (SPLDA) model. This can be used to adapt SPLDA from one database to another with few development data or to implement the fully Bayesian recipe. Our approach is similar to Bishop's VB PPCA.

  7. An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians.

    Science.gov (United States)

    Hanson, R L; Ehm, M G; Pettitt, D J; Prochazka, M; Thompson, D B; Timberlake, D; Foroud, T; Kobes, S; Baier, L; Burns, D K; Almasy, L; Blangero, J; Garvey, W T; Bennett, P H; Knowler, W C

    1998-01-01

    Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q. PMID:9758619

  8. Scanning for genes in large genomic regions: cosmid-based exon trapping of multiple exons in a single product.

    Science.gov (United States)

    Datson, N A; van de Vosse, E; Dauwerse, H G; Bout, M; van Ommen, G J; den Dunnen, J T

    1996-03-15

    To facilitate the scanning of large genomic regions for the presence of exonic gene segments we have constructed a cosmid-based exon trap vector. The vector serves a dual purpose since it is also suitable for contig construction and physical mapping. The exon trap cassette of vector sCOGH1 consists of the human growth hormone gene driven by the mouse mettallothionein-1 promoter. Inserts are cloned in the multicloning site located in intron 2 of the hGH gene. The efficiency of the system is demonstrated with cosmids containing multiple exons of the Duchenne Muscular Dystrophy gene. All exons present in the inserts were successfully retrieved and no cryptic products were detected. Up to seven exons were isolated simultaneously in a single spliced product. The system has been extended by a transcription-translation-test protocol to determine the presence of large open reading frames in the trapped products, using a combination of tailed PCR primers directing protein synthesis in three different reading frames, followed by in vitro transcription-translation. Having larger stretches of coding sequence in a single exon trap product rather than small single exons greatly facilitates further analysis of potential genes and offers new possibilities for direct mutation analysis of exon trap material.

  9. Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia.

    Science.gov (United States)

    Austin, Melissa A; Edwards, Karen L; Monks, Stephanie A; Koprowicz, Kent M; Brunzell, John D; Motulsky, Arno G; Mahaney, Michael C; Hixson, James E

    2003-11-01

    Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The objective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and genotyping was performed for 355 autosomal markers with an average heterozygosity of 76% and an average spacing of 10.2 centimorgans (cMs). Using variance components linkage analysis, one possible linkage was found for LDL size [logarithm of odds (LOD) = 2.1] on chromosome 6, peak at 140 cM distal to marker F13A1 (closest marker D6S2436). With adjustment for TG and/or HDL cholesterol, the LOD scores were reduced, but remained in exactly the same location. For TG, LOD scores of 2.56 and 2.44 were observed at two locations on chromosome 15, with peaks at 29 and 61 cM distal to marker D15S822 (closest markers D15S643 and D15S211, respectively). These peaks were retained with adjustment for LDL size and/or HDL cholesterol. These findings, if confirmed, suggest that LDL particle size and plasma TG levels could be caused by two different genetic loci in FHTG.

  10. Bayesian signaling

    OpenAIRE

    Hedlund, Jonas

    2014-01-01

    This paper introduces private sender information into a sender-receiver game of Bayesian persuasion with monotonic sender preferences. I derive properties of increasing differences related to the precision of signals and use these to fully characterize the set of equilibria robust to the intuitive criterion. In particular, all such equilibria are either separating, i.e., the sender's choice of signal reveals his private information to the receiver, or fully disclosing, i.e., the outcome of th...

  11. Bayesian Monitoring.

    OpenAIRE

    Kirstein, Roland

    2005-01-01

    This paper presents a modification of the inspection game: The ?Bayesian Monitoring? model rests on the assumption that judges are interested in enforcing compliant behavior and making correct decisions. They may base their judgements on an informative but imperfect signal which can be generated costlessly. In the original inspection game, monitoring is costly and generates a perfectly informative signal. While the inspection game has only one mixed strategy equilibrium, three Perfect Bayesia...

  12. Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

    DEFF Research Database (Denmark)

    Huyghe, J.R.; Laer, L. Van; Hendrickx, J.J.

    2008-01-01

    the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We...... conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were...

  13. Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees

    Science.gov (United States)

    Moser, Kathy L.; Neas, Barbara R.; Salmon, Jane E.; Yu, Hua; Gray-McGuire, Courtney; Asundi, Neeraj; Bruner, Gail R.; Fox, Jerome; Kelly, Jennifer; Henshall, Stephanie; Bacino, Debra; Dietz, Myron; Hogue, Robert; Koelsch, Gerald; Nightingale, Lydia; Shaver, Tim; Abdou, Nabih I.; Albert, Daniel A.; Carson, Craig; Petri, Michelle; Treadwell, Edward L.; James, Judith A.; Harley, John B.

    1998-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcγ receptors (FcγR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, λs > 10, purported linkage at 1q41–42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14–23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26–27, and 12p12–11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcγRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects. PMID:9843982

  14. Bayesian programming

    CERN Document Server

    Bessiere, Pierre; Ahuactzin, Juan Manuel; Mekhnacha, Kamel

    2013-01-01

    Probability as an Alternative to Boolean LogicWhile logic is the mathematical foundation of rational reasoning and the fundamental principle of computing, it is restricted to problems where information is both complete and certain. However, many real-world problems, from financial investments to email filtering, are incomplete or uncertain in nature. Probability theory and Bayesian computing together provide an alternative framework to deal with incomplete and uncertain data. Decision-Making Tools and Methods for Incomplete and Uncertain DataEmphasizing probability as an alternative to Boolean

  15. 畜禽基因组选择中贝叶斯方法及其参数优化策略%The Strategy of Parameter Optimization of Bayesian Methods for Genomic Selection in Livestock

    Institute of Scientific and Technical Information of China (English)

    朱波; 王延晖; 牛红; 陈燕; 张路培; 高会江; 高雪; 李俊雅; 孙少华

    2014-01-01

    Variety selection in livestock breeding occupies an important position. Genomic selection, as a novel technology in livestock breeding, has raised considerable concern. It can shorten the generation interval, speed up the genetic progress, and it can select the candidate individuals as breeding stock without phenotypic data. In 2001, Meuviwisen proposed the concept of genomic selection, which was first applied in dairy cattle. Until August 2014, there were 34 member countries of Interbull organization that had applicated genomic selection in their national dairy cattle breeding group. With the popularization and continuous promotion of genomic selection, some problems of the accuracy of genomic estimated breeding value need to be solved. Various methods of genomic selection have been proposed and more efficient models are being developed. So it has great practical significance to exploit better models and algorithm to improve the accuracy of genomic estimated breeding value. So far, there were 17 Bayesian methods that have been successively proposed. This thesis briefly introduced the classical BayesA and BayesB methods for genomic selection. BayesA assumed that all loca have effect, while BayesB supposed that a small part of locus have effect, and the percentage was extremely small. Therefore, BayesA and BayesB had different models and algorithms. After Meuviwisen proposed classic Bayesian methods, other methods were like mushrooms springing up. New Bayesian methods were based on the classical Bayesian methods, which was optimized by improving the hypothetical model and algorithm. For example, BayesC method, which was based on BayesB, optimized theπvalue in the model. BayesCπ and BayesDπ were the improvement of BayesC, and these two approaches assumed that marker effect variance of each locus had the same value, whereas BayesC assumed that its marker effect variance of each locus was different. BayesDπ, which was based on BayesCπ, optimized the scale

  16. Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

    Science.gov (United States)

    Phasukkijwatana, Nopasak; Kunhapan, Bussaraporn; Stankovich, Jim; Chuenkongkaew, Wanicha L; Thomson, Russell; Thornton, Timothy; Bahlo, Melanie; Mushiroda, Taisei; Nakamura, Yusuke; Mahasirimongkol, Surakameth; Tun, Aung Win; Srisawat, Chatchawan; Limwongse, Chanin; Peerapittayamongkol, Chayanon; Sura, Thanyachai; Suthammarak, Wichit; Lertrit, Patcharee

    2010-07-01

    Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

  17. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    Science.gov (United States)

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems. © 2015 Blackwell Verlag GmbH.

  18. Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11.

    Science.gov (United States)

    Pato, Carlos N; Pato, M T; Kirby, A; Petryshen, T L; Medeiros, H; Carvalho, C; Macedo, A; Dourado, A; Coelho, I; Valente, J; Soares, M J; Ferreira, C P; Lei, M; Verner, A; Hudson, T J; Morley, C P; Kennedy, J L; Azevedo, M H; Daly, M J; Sklar, P

    2004-05-15

    As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley-Liss, Inc.

  19. Scanning genomic areas under selection sweep and association mapping as tools to identify horticultural important genes in watermelon

    Science.gov (United States)

    Watermelon (Citrullus lanatus var. lanatus) contains 88% water, sugars, and several important health-related compounds, including lycopene, citrulline, arginine, and glutathione. The current genetic diversity study uses microsatellites with known map positions to identify genomic regions that under...

  20. A genome-wide scan of selective sweeps in two broiler chicken lines divergently selected for abdominal fat content.

    Science.gov (United States)

    Zhang, Hui; Wang, Shou-Zhi; Wang, Zhi-Peng; Da, Yang; Wang, Ning; Hu, Xiao-Xiang; Zhang, Yuan-Dan; Wang, Yu-Xiang; Leng, Li; Tang, Zhi-Quan; Li, Hui

    2012-12-15

    Genomic regions controlling abdominal fatness (AF) were studied in the Northeast Agricultural University broiler line divergently selected for AF. In this study, the chicken 60KSNP chip and extended haplotype homozygosity (EHH) test were used to detect genome-wide signatures of AF. A total of 5357 and 5593 core regions were detected in the lean and fat lines, and 51 and 57 reached a significant level (Pchickens. We provide a genome-wide map of selection signatures in the chicken genome, and make a contribution to the better understanding the mechanisms of selection for AF content in chickens. The selection for low AF in commercial breeding using this information will accelerate the breeding progress.

  1. Introduction to Bayesian statistics

    CERN Document Server

    Bolstad, William M

    2017-01-01

    There is a strong upsurge in the use of Bayesian methods in applied statistical analysis, yet most introductory statistics texts only present frequentist methods. Bayesian statistics has many important advantages that students should learn about if they are going into fields where statistics will be used. In this Third Edition, four newly-added chapters address topics that reflect the rapid advances in the field of Bayesian staistics. The author continues to provide a Bayesian treatment of introductory statistical topics, such as scientific data gathering, discrete random variables, robust Bayesian methods, and Bayesian approaches to inferenfe cfor discrete random variables, bionomial proprotion, Poisson, normal mean, and simple linear regression. In addition, newly-developing topics in the field are presented in four new chapters: Bayesian inference with unknown mean and variance; Bayesian inference for Multivariate Normal mean vector; Bayesian inference for Multiple Linear RegressionModel; and Computati...

  2. Bayesian artificial intelligence

    CERN Document Server

    Korb, Kevin B

    2010-01-01

    Updated and expanded, Bayesian Artificial Intelligence, Second Edition provides a practical and accessible introduction to the main concepts, foundation, and applications of Bayesian networks. It focuses on both the causal discovery of networks and Bayesian inference procedures. Adopting a causal interpretation of Bayesian networks, the authors discuss the use of Bayesian networks for causal modeling. They also draw on their own applied research to illustrate various applications of the technology.New to the Second EditionNew chapter on Bayesian network classifiersNew section on object-oriente

  3. Bayesian artificial intelligence

    CERN Document Server

    Korb, Kevin B

    2003-01-01

    As the power of Bayesian techniques has become more fully realized, the field of artificial intelligence has embraced Bayesian methodology and integrated it to the point where an introduction to Bayesian techniques is now a core course in many computer science programs. Unlike other books on the subject, Bayesian Artificial Intelligence keeps mathematical detail to a minimum and covers a broad range of topics. The authors integrate all of Bayesian net technology and learning Bayesian net technology and apply them both to knowledge engineering. They emphasize understanding and intuition but also provide the algorithms and technical background needed for applications. Software, exercises, and solutions are available on the authors' website.

  4. Bayesian Graphical Models

    DEFF Research Database (Denmark)

    Jensen, Finn Verner; Nielsen, Thomas Dyhre

    2016-01-01

    Mathematically, a Bayesian graphical model is a compact representation of the joint probability distribution for a set of variables. The most frequently used type of Bayesian graphical models are Bayesian networks. The structural part of a Bayesian graphical model is a graph consisting of nodes...... is largely due to the availability of efficient inference algorithms for answering probabilistic queries about the states of the variables in the network. Furthermore, to support the construction of Bayesian network models, learning algorithms are also available. We give an overview of the Bayesian network...

  5. Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition

    Directory of Open Access Journals (Sweden)

    Moradi Mohammad Hossein

    2012-02-01

    Full Text Available Abstract Background Identification of genomic regions that have been targets of selection for phenotypic traits is one of the most important and challenging areas of research in animal genetics. However, currently there are relatively few genomic regions identified that have been subject to positive selection. In this study, a genome-wide scan using ~50,000 Single Nucleotide Polymorphisms (SNPs was performed in an attempt to identify genomic regions associated with fat deposition in fat-tail breeds. This trait and its modification are very important in those countries grazing these breeds. Results Two independent experiments using either Iranian or Ovine HapMap genotyping data contrasted thin and fat tail breeds. Population differentiation using FST in Iranian thin and fat tail breeds revealed seven genomic regions. Almost all of these regions overlapped with QTLs that had previously been identified as affecting fat and carcass yield traits in beef and dairy cattle. Study of selection sweep signatures using FST in thin and fat tail breeds sampled from the Ovine HapMap project confirmed three of these regions located on Chromosomes 5, 7 and X. We found increased homozygosity in these regions in favour of fat tail breeds on chromosome 5 and X and in favour of thin tail breeds on chromosome 7. Conclusions In this study, we were able to identify three novel regions associated with fat deposition in thin and fat tail sheep breeds. Two of these were associated with an increase of homozygosity in the fat tail breeds which would be consistent with selection for mutations affecting fat tail size several thousand years after domestication.

  6. A Bayesian outlier criterion to detect SNPs under selection in large data sets.

    Directory of Open Access Journals (Sweden)

    Mathieu Gautier

    Full Text Available BACKGROUND: The recent advent of high-throughput SNP genotyping technologies has opened new avenues of research for population genetics. In particular, a growing interest in the identification of footprints of selection, based on genome scans for adaptive differentiation, has emerged. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study is to develop an efficient model-based approach to perform bayesian exploratory analyses for adaptive differentiation in very large SNP data sets. The basic idea is to start with a very simple model for neutral loci that is easy to implement under a bayesian framework and to identify selected loci as outliers via Posterior Predictive P-values (PPP-values. Applications of this strategy are considered using two different statistical models. The first one was initially interpreted in the context of populations evolving respectively under pure genetic drift from a common ancestral population while the second one relies on populations under migration-drift equilibrium. Robustness and power of the two resulting bayesian model-based approaches to detect SNP under selection are further evaluated through extensive simulations. An application to a cattle data set is also provided. CONCLUSIONS/SIGNIFICANCE: The procedure described turns out to be much faster than former bayesian approaches and also reasonably efficient especially to detect loci under positive selection.

  7. Whole-genome scan for quantitative trait loci associated with birth weight, gestation length and passive immune transfer in a Holstein x Jersey crossbred population.

    Science.gov (United States)

    Maltecca, C; Weigel, K A; Khatib, H; Cowan, M; Bagnato, A

    2009-02-01

    We herein report results from a daughter design genome-scan study aiming to identify quantitative trait loci (QTL) associated with birth weight, direct gestation length and passive immune transfer in a backcross (Holstein x Jersey) x Holstein population. Two-hundred and seventy-six calves, offspring of seven crossbred sires, were genotyped for 161 microsatellite markers distributed along the 29 bovine autosomes. The genome scan was performed through interval mapping using an animal model in order to identify QTL accounting for phenotypic differences between individual animals. Based on significant chi-squared values, we identified putative QTL on BTA7 and BTA14 for gestation length, on BTA2, BTA6 and BTA14 for birth weight and on BTA20 for passive immune transfer. In total, these QTL accounted for 12%, 18% and 1% of the phenotypic variance in gestation length, birth weight and passive immune transfer respectively. We also report results from a supplementary and independent influential grand-daughter Holstein family. In this family, findings on BTA7 and BTA14 for direct gestation length were in agreement with results in the crossbred population. Two other regions on BTA6 and BTA21 putatively underlying QTL for direct gestation length variability were discovered with this analysis.

  8. A whole genome scan to detect quantitative trait loci for gestation length and sow maternal ability related traits in a White Duroc × Erhualian F2 resource population.

    Science.gov (United States)

    Chen, C Y; Guo, Y M; Zhang, Z Y; Ren, J; Huang, L S

    2010-06-01

    Gestation length and maternal ability are important to improve the sow reproduction efficiency and their offspring survival. To map quantitative trait loci (QTL) for gestation length and maternal ability related traits including piglet survival rate and average body weight of piglets at weaning, more than 200 F2 sows from a White Duroc × Erhualian resource population were phenotyped. A genome-wide scan was performed with 194 microsatellite markers covering the whole pig genome. QTL analysis was carried out using a composite regression interval mapping method via QTL express. The results showed that total number of born piglets was significantly correlated with gestation length (r = -0.13, P gestation length. The QTL on SSC2 achieved the 5% genome-wide significant level and the QTL on SSC8 was consistent with previous reports. Four suggestive QTL were identified for maternal ability related traits including 1 QTL for survival rate of piglets at weaning on SSC8, 3 QTL for average body weight of piglet at weaning on SSC3, 11 and 13.

  9. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

    OpenAIRE

    Nicola Pirastu; Maarten Kooyman; Antonietta Robino; Ashley van der Spek; Luciano Navarini; Najaf Amin; Lennart C. Karssen; Cornelia M van Duijn; Paolo Gasparini

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using...

  10. Applied Bayesian Hierarchical Methods

    CERN Document Server

    Congdon, Peter D

    2010-01-01

    Bayesian methods facilitate the analysis of complex models and data structures. Emphasizing data applications, alternative modeling specifications, and computer implementation, this book provides a practical overview of methods for Bayesian analysis of hierarchical models.

  11. Genome-wide linkage scan for primary open angle glaucoma: influences of ancestry and age at diagnosis.

    Directory of Open Access Journals (Sweden)

    Kristy R Crooks

    Full Text Available Primary open-angle glaucoma (POAG is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry. Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry. Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15--were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.

  12. Family based genome-wide copy number scan identifies complex rearrangements at 17q21.31 in dyslexics.

    Science.gov (United States)

    Veerappa, Avinash M; Saldanha, Marita; Padakannaya, Prakash; Ramachandra, Nallur B

    2014-10-01

    Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed genome-wide screening for copy number variations (CNVs) in 10 large Indian dyslexic families using Affymetrix Genome-Wide Human SNP Array 6.0. Results revealed the complex genomic rearrangements due to one non-contiguous deletion and five contiguous micro duplications and micro deletions at 17q21.31 region in three dyslexic families. CNVs in this region harbor the genes KIAA1267, LRRC37A, ARL17A/B, NSFP1, and NSF. The CNVs in case 1 and case 2 at this locus were found to be in homozygous state and case 3 was a de novo CNV. These CNVs were found with at least one CNV having a common break and end points in the parents. This cluster of genes containing NSF is implicated in learning, cognition, and memory, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia related module genes suggests NSF and other genes to be associated with cellular/vesicular membrane fusion and synaptic transmission. Thus, we suggest that NSF in this cluster would be the nearest gene responsible for the learning disability phenotype.

  13. Bayesian data analysis

    CERN Document Server

    Gelman, Andrew; Stern, Hal S; Dunson, David B; Vehtari, Aki; Rubin, Donald B

    2013-01-01

    FUNDAMENTALS OF BAYESIAN INFERENCEProbability and InferenceSingle-Parameter Models Introduction to Multiparameter Models Asymptotics and Connections to Non-Bayesian ApproachesHierarchical ModelsFUNDAMENTALS OF BAYESIAN DATA ANALYSISModel Checking Evaluating, Comparing, and Expanding ModelsModeling Accounting for Data Collection Decision AnalysisADVANCED COMPUTATION Introduction to Bayesian Computation Basics of Markov Chain Simulation Computationally Efficient Markov Chain Simulation Modal and Distributional ApproximationsREGRESSION MODELS Introduction to Regression Models Hierarchical Linear

  14. AFLP genome scan to detect genetic structure and candidate loci under selection for local adaptation of the invasive weed Mikania micrantha.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Why some species become successful invaders is an important issue in invasive biology. However, limited genomic resources make it very difficult for identifying candidate genes involved in invasiveness. Mikania micrantha H.B.K. (Asteraceae, one of the world's most invasive weeds, has adapted rapidly in response to novel environments since its introduction to southern China. In its genome, we expect to find outlier loci under selection for local adaptation, critical to dissecting the molecular mechanisms of invasiveness. An explorative amplified fragment length polymorphism (AFLP genome scan was used to detect candidate loci under selection in 28 M. micrantha populations across its entire introduced range in southern China. We also estimated population genetic parameters, bottleneck signatures, and linkage disequilibrium. In binary characters, such as presence or absence of AFLP bands, if all four character combinations are present, it is referred to as a character incompatibility. Since character incompatibility is deemed to be rare in populations with extensive asexual reproduction, a character incompatibility analysis was also performed in order to infer the predominant mating system in the introduced M. micrantha populations. Out of 483 AFLP loci examined using stringent significance criteria, 14 highly credible outlier loci were identified by Dfdist and Bayescan. Moreover, remarkable genetic variation, multiple introductions, substantial bottlenecks and character compatibility were found to occur in M. micrantha. Thus local adaptation at the genome level indeed exists in M. micrantha, and may represent a major evolutionary mechanism of successful invasion. Interactions between genetic diversity, multiple introductions, and reproductive modes contribute to increase the capacity of adaptive evolution.

  15. Five blood pressure loci identified by an updated genome-wide linkage scan: meta-analysis of the Family Blood Pressure Program.

    Science.gov (United States)

    Simino, Jeannette; Shi, Gang; Kume, Rezart; Schwander, Karen; Province, Michael A; Gu, C Charles; Kardia, Sharon; Chakravarti, Aravinda; Ehret, Georg; Olshen, Richard A; Turner, Stephen T; Ho, Low-Tone; Zhu, Xiaofeng; Jaquish, Cashell; Paltoo, Dina; Cooper, Richard S; Weder, Alan; Curb, J David; Boerwinkle, Eric; Hunt, Steven C; Rao, Dabeeru C

    2011-03-01

    A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension. We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups. Five quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score ≥3) in at least one meta-analysis and lod scores ≥1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. The new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.

  16. Whole-genome scan to detect quantitative trait loci associated with milk protein composition in 3 French dairy cattle breeds.

    Science.gov (United States)

    Sanchez, M P; Govignon-Gion, A; Ferrand, M; Gelé, M; Pourchet, D; Amigues, Y; Fritz, S; Boussaha, M; Capitan, A; Rocha, D; Miranda, G; Martin, P; Brochard, M; Boichard, D

    2016-10-01

    In the context of the PhénoFinLait project, a genome-wide analysis was performed to detect quantitative trait loci (QTL) that affect milk protein composition estimated using mid-infrared spectrometry in the Montbéliarde (MO), Normande (NO), and Holstein (HO) French dairy cattle breeds. The 6 main milk proteins (α-lactalbumin, β-lactoglobulin, and αS1-, αS2-, β-, and κ-caseins) expressed as grams per 100g of milk (% of milk) or as grams per 100g of protein (% of protein) were estimated in 848,068 test-day milk samples from 156,660 cows. Genotyping was performed for 2,773 MO, 2,673 NO, and 2,208 HO cows using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). Individual test-day records were adjusted for environmental effects and then averaged per cow to define the phenotypes analyzed. Quantitative trait loci detection was performed within each breed using a linkage disequilibrium and linkage analysis approach. A total of 39 genomic regions distributed on 20 of the 29 Bos taurus autosomes (BTA) were significantly associated with milk protein composition at a genome-wide level of significance in at least 1 of the 3 breeds. The 9 most significant QTL were located on BTA2 (133 Mbp), BTA6 (38, 47, and 87 Mbp), BTA11 (103 Mbp), BTA14 (1.8 Mbp), BTA20 (32 and 58 Mbp), and BTA29 (8 Mbp). The BTA6 (87 Mbp), BTA11, and BTA20 (58 Mbp) QTL were found in all 3 breeds, and they had highly significant effects on κ-casein, β-lactoglobulin, and α-lactalbumin, expressed as a percentage of protein, respectively. Each of these QTL explained between 13% (BTA14) and 51% (BTA11) of the genetic variance of the trait. Many other QTL regions were also identified in at least one breed. They were located on 14 additional chromosomes (1, 3, 4, 5, 7, 15, 17, 19, 21, 22, 24, 25, 26, and 27), and they explained 2 to 8% of the genetic variance of 1 or more protein composition traits. Concordance analyses, performed between QTL status and sequence-derived polymorphisms from

  17. Genome scan for cognitive trait loci of dyslexia: rapid naming and rapid switching of letters, numbers, and colors

    Science.gov (United States)

    Rubenstein, Kevin; Raskind, Wendy H.; Berninger, Virginia W.; Matsushita, Mark M.; Wijsman, Ellen M.

    2014-01-01

    Dyslexia, or specific reading disability, is a common developmental disorder that affects 5–12% of school-aged children. Dyslexia and its component phenotypes, assessed categorically or quantitatively, have complex genetic bases. The ability to rapidly name letters, numbers, and colors from rows presented visually correlates strongly with reading in multiple languages and is a valid predictor of reading and spelling impairment. Performance on measures of rapid naming and switching, RAN and RAS, is stable throughout elementary school years, with slowed performance persisting in adults who still manifest dyslexia. Targeted analyses of dyslexia candidate regions have included RAN measures, but only one other genome-wide linkage study has been reported. As part of a broad effort to identify genetic contributors to dyslexia, we performed combined oligogenic segregation and linkage analyses of measures of RAN and RAS in a family-based cohort ascertained through probands with dyslexia. We obtained strong evidence for linkage of RAN letters to the DYX3 locus on chromosome 2p and RAN colors to chromosome 10q, but were unable to confirm the chromosome 6p21 linkage detected for a composite measure of RAN colors and objects in the previous genome-wide study. PMID:24807833

  18. Genome scanning for interspecific differentiation between two closely related oak species [Quercus robur L. and Q. petraea (Matt.) Liebl.].

    Science.gov (United States)

    Scotti-Saintagne, Caroline; Mariette, Stéphanie; Porth, Ilga; Goicoechea, Pablo G; Barreneche, Teresa; Bodénès, Catherine; Burg, Kornel; Kremer, Antoine

    2004-11-01

    Interspecific differentiation values (G(ST)) between two closely related oak species (Quercus petraea and Q. robur) were compiled across different studies with the aim to explore the distribution of differentiation at the genome level. The study was based on a total set of 389 markers (isozymes, AFLPs, SCARs, microsatellites, and SNPs) for which allelic frequencies were estimated in pairs of populations sampled throughout the sympatric distribution of the two species. The overall distribution of G(ST) values followed an L-shaped curve with most markers exhibiting low species differentiation (G(ST) 10% levels. Twelve percent of the loci exhibited significant G(ST) deviations to neutral expectations, suggesting that selection contributed to species divergence. Coding regions expressed higher differentiation than noncoding regions. Among the 389 markers, 158 could be mapped on the 12 linkage groups of the existing Q. robur genetic map. Outlier loci with large G(ST) values were distributed over 9 linkage groups. One cluster of three outlier loci was found within 0.51 cM; but significant autocorrelation of G(ST) was observed at distances <2 cM. The size and distribution of genomic regions involved in species divergence are discussed in reference to hitchhiking effects and disruptive selection.

  19. Genome scan for cognitive trait loci of dyslexia: Rapid naming and rapid switching of letters, numbers, and colors.

    Science.gov (United States)

    Rubenstein, Kevin B; Raskind, Wendy H; Berninger, Virginia W; Matsushita, Mark M; Wijsman, Ellen M

    2014-06-01

    Dyslexia, or specific reading disability, is a common developmental disorder that affects 5-12% of school-aged children. Dyslexia and its component phenotypes, assessed categorically or quantitatively, have complex genetic bases. The ability to rapidly name letters, numbers, and colors from rows presented visually correlates strongly with reading in multiple languages and is a valid predictor of reading and spelling impairment. Performance on measures of rapid naming and switching, RAN and RAS, is stable throughout elementary school years, with slowed performance persisting in adults who still manifest dyslexia. Targeted analyses of dyslexia candidate regions have included RAN measures, but only one other genome-wide linkage study has been reported. As part of a broad effort to identify genetic contributors to dyslexia, we performed combined oligogenic segregation and linkage analyses of measures of RAN and RAS in a family-based cohort ascertained through probands with dyslexia. We obtained strong evidence for linkage of RAN letters to the DYX3 locus on chromosome 2p and RAN colors to chromosome 10q, but were unable to confirm the chromosome 6p21 linkage detected for a composite measure of RAN colors and objects in the previous genome-wide study. © 2014 Wiley Periodicals, Inc.

  20. Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods.

    Directory of Open Access Journals (Sweden)

    Yuri Tani Utsunomiya

    Full Text Available As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP data generated from dairy and beef cattle (taurine and indicine. The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7 population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3 in Brown Swiss (P = 3.82×10(-12, and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

  1. Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases.

    Directory of Open Access Journals (Sweden)

    Roberto Amato

    Full Text Available Genetic differences both between individuals and populations are studied for their evolutionary relevance and for their potential medical applications. Most of the genetic differentiation among populations are caused by random drift that should affect all loci across the genome in a similar manner. When a locus shows extraordinary high or low levels of population differentiation, this may be interpreted as evidence for natural selection. The most used measure of population differentiation was devised by Wright and is known as fixation index, or F(ST. We performed a genome-wide estimation of F(ST on about 4 millions of SNPs from HapMap project data. We demonstrated a heterogeneous distribution of F(ST values between autosomes and heterochromosomes. When we compared the F(ST values obtained in this study with another evolutionary measure obtained by comparative interspecific approach, we found that genes under positive selection appeared to show low levels of population differentiation. We applied a gene set approach, widely used for microarray data analysis, to detect functional pathways under selection. We found that one pathway related to antigen processing and presentation showed low levels of F(ST, while several pathways related to cell signalling, growth and morphogenesis showed high F(ST values. Finally, we detected a signature of selection within genes associated with human complex diseases. These results can help to identify which process occurred during human evolution and adaptation to different environments. They also support the hypothesis that common diseases could have a genetic background shaped by human evolution.

  2. Sex-specific variability and a 'cage effect' independently mask a neuropathic pain quantitative trait locus detected in a whole genome scan.

    Science.gov (United States)

    Devor, Marshall; Gilad, Amit; Arbilly, Michal; Nissenbaum, Jonathan; Yakir, Benjamin; Raber, Pnina; Minert, Anne; Pisanté, Anne; Darvasi, Ariel

    2007-08-01

    Sex and environment may dramatically affect genetic studies, and thus should be carefully considered. Beginning with two inbred mouse strains with contrasting phenotype in the neuroma model of neuropathic pain (autotomy), we established a backcross population on which we conducted a genome-wide scan. The backcross population was partially maintained in small social groups and partially in isolation. The genome scan detected one previously reported quantitative trait locus (QTL) on chromosome 15 (pain1), but no additional QTLs were found. Interestingly, group caging introduced phenotypic noise large enough to completely mask the genetic effect of the chromosome 15 QTL. The reason appears to be that group-caging animals from the low-autotomy strain together with animals from the high-autotomy strain dramatically increases autotomy in the otherwise low-autotomy mice (males or females). The converse, suppression of pain behaviour in the high-autotomy strain when caged with the low-autotomy strain was also observed, but only in females. Even in isolated mice, the genetic effect of the chromosome 15 QTL was significant only in females. To determine why, we evaluated autotomy levels of females in 12 different inbred stains of mice and compared them to previously reported levels for males. Strikingly larger environmental variation was observed in males than in females for this pain phenotype. The high baseline variance in males can explain the difficulty in detecting the genetic effect, which was readily seen in females. Our study emphasizes the importance of sex and environment in the genetic analysis of pain.

  3. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

    Science.gov (United States)

    Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez, Mirsha; Mendoza-Revilla, Javier; Camilo Chacón-Duque, Juan; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Lozano, Rodrigo Barquera; Pérez, Gastón Macín; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria- Cátira; Canizales-Quinteros, Samuel; Cheeseman, Michael; Rosique, Javier; Bedoya, Gabriel; Rothhammer, Francisco; Headon, Denis; González-José, Rolando; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. PMID:27193062

  4. A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries).

    Science.gov (United States)

    Li, M-H; Tiirikka, T; Kantanen, J

    2014-02-01

    In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10(-11) for all the colours; P=2.3 × 10(-11) for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding.

  5. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.

    Directory of Open Access Journals (Sweden)

    Nicole Soranzo

    2009-04-01

    Full Text Available Recent genome-wide (GW scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8 and rs910316 in TMED10, P-value = 1.4x10(-7 and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7 and rs849141 in JAZF1, P-value = 3.2x10(-11. One locus (rs1182188 at GNA12 identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk and lower-body (hip axis and femur skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5 and rs6817306 in LCORL, P-value = 4x10(-4, hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4 and rs4911494 at UQCC, P-value = 1.9x10(-4, and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5 and rs10946808 at HIST1H1D, P-value = 6.4x10(-6. Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height.

  6. GeneRegionScan: a Bioconductor package for probe-level analysis of specific, small regions of the genome.

    Science.gov (United States)

    Folkersen, Lasse; Diez, Diego; Wheelock, Craig E; Haeggström, Jesper Z; Goto, Susumu; Eriksson, Per; Gabrielsen, Anders

    2009-08-01

    Whole-genome microarrays allow us to interrogate the entire transcriptome of a cell. Affymetrix microarrays are constructed using several probes that match to different regions of a gene and a summarization step reduces this complexity into a single value, representing the expression level of the gene or the expression level of an exon in the case of exon arrays. However, this simplification eliminates information that might be useful when focusing on specific genes of interest. To address these limitations, we present a software package for the R platform that allows detailed analysis of expression at the probe level. The package matches the probe sequences against a target gene sequence (either mRNA or DNA) and shows the expression levels of each probe along the gene. It also features functions to fit a linear regression based on several genetic models that enables study of the relationship between gene expression and genotype. The software is implemented as a platform-independent R package available through the Bioconductor repository at http://www.bioconductor.org/. It is licensed as GPL 2.0. Supplementary data are available at Bioinformatics online.

  7. Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

    Directory of Open Access Journals (Sweden)

    Gray Joanna

    2010-11-01

    Full Text Available Abstract Background We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism microarrays and DNA pooling (SNP-MaP employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations. The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred.

  8. Genome-wide scan for bats and dolphin to detect their genetic basis for new locomotive styles.

    Directory of Open Access Journals (Sweden)

    Yong-Yi Shen

    Full Text Available For most mammals, running is their major locomotive style, however, cetaceans and bats are two mammalian groups that have independently developed new locomotive styles (swimming and flying from their terrestrial ancestors. In this study, we used a genome-wide comparative analysis in an attempt to identify the selective imprint of the development of new locomotive styles by cetaceans and bats to adapt to their new ecological niches. We found that an elevated proportion of mitochondrion-associated genes show evidence of adaptive evolution in cetaceans and on the common ancestral lineage leading to bats, compared to other terrestrial mammals. This result is consistent with the fact that during the independent developments of swimming and flying in these two groups, the changes of energy metabolism ratios would be among the most important factors to overcome elevated energy demands. Furthermore, genes that show evidence of sequence convergence or parallel evolution in these two lineages were overrepresented in the categories of energy metabolism, muscle contraction, heart, and glucose metabolism, genes that perform functions which are essential for locomotion. In conclusion, our analyses showed that on the dolphin and bat lineages, genes associated with locomotion not only both show a greater propensity to adaptively evolve, but also show evidence of sequence convergence, which likely reflects a response to a common requirement during their development of these two drastic locomotive styles.

  9. AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

    Science.gov (United States)

    Tollenaere, C; Duplantier, J-M; Rahalison, L; Ranjalahy, M; Brouat, C

    2011-03-01

    The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

  10. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia.

    Science.gov (United States)

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-12-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species.

  11. Asymmetric Introgression in the Horticultural Living Fossil Cycas Sect. Asiorientales Using a Genome-Wide Scanning Approach

    Directory of Open Access Journals (Sweden)

    Shong Huang

    2013-04-01

    Full Text Available The Asian cycads are mostly allopatric, distributed in small population sizes. Hybridization between allopatric species provides clues in determining the mechanism of species divergence. Horticultural introduction provides the chance of interspecific gene flow between allopatric species. Two allopatrically eastern Asian Cycas sect. Asiorientales species, C. revoluta and C. taitungensis, which are widely distributed in Ryukyus and Fujian Province and endemic to Taiwan, respectively, were planted in eastern Taiwan for horticultural reason. Higher degrees of genetic admixture in cultivated samples than wild populations in both cycad species were detected based on multilocus scans by neutral AFLP markers. Furthermore, bidirectional but asymmetric introgression by horticultural introduction of C. revoluta is evidenced by the reanalyses of species associated loci, which are assumed to be diverged after species divergence. Partial loci introgressed from native cycad to the invaders were also detected at the loci of strong species association. Consistent results tested by all neutral loci, and the species-associated loci, specify the recent introgression from the paradox of sharing of ancestral polymorphisms. Phenomenon of introgression of cultivated cycads implies niche conservation among two geographic-isolated cycads, even though the habitats of the extant wild populations of two species are distinct.

  12. A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.

    Directory of Open Access Journals (Sweden)

    Yin-Ju Lien

    Full Text Available BACKGROUND: As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits. METHODS: Patients with schizophrenia (n  =  1,207 and their first-degree relatives (n  =  1,035 from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT, the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome. RESULTS: A maximum nonparametric logarithm of odds (LOD score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively. CONCLUSION: We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia.

  13. Nonparametric Bayesian inference in biostatistics

    CERN Document Server

    Müller, Peter

    2015-01-01

    As chapters in this book demonstrate, BNP has important uses in clinical sciences and inference for issues like unknown partitions in genomics. Nonparametric Bayesian approaches (BNP) play an ever expanding role in biostatistical inference from use in proteomics to clinical trials. Many research problems involve an abundance of data and require flexible and complex probability models beyond the traditional parametric approaches. As this book's expert contributors show, BNP approaches can be the answer. Survival Analysis, in particular survival regression, has traditionally used BNP, but BNP's potential is now very broad. This applies to important tasks like arrangement of patients into clinically meaningful subpopulations and segmenting the genome into functionally distinct regions. This book is designed to both review and introduce application areas for BNP. While existing books provide theoretical foundations, this book connects theory to practice through engaging examples and research questions. Chapters c...

  14. Bayesian Games with Intentions

    Directory of Open Access Journals (Sweden)

    Adam Bjorndahl

    2016-06-01

    Full Text Available We show that standard Bayesian games cannot represent the full spectrum of belief-dependent preferences. However, by introducing a fundamental distinction between intended and actual strategies, we remove this limitation. We define Bayesian games with intentions, generalizing both Bayesian games and psychological games, and prove that Nash equilibria in psychological games correspond to a special class of equilibria as defined in our setting.

  15. Understanding Computational Bayesian Statistics

    CERN Document Server

    Bolstad, William M

    2011-01-01

    A hands-on introduction to computational statistics from a Bayesian point of view Providing a solid grounding in statistics while uniquely covering the topics from a Bayesian perspective, Understanding Computational Bayesian Statistics successfully guides readers through this new, cutting-edge approach. With its hands-on treatment of the topic, the book shows how samples can be drawn from the posterior distribution when the formula giving its shape is all that is known, and how Bayesian inferences can be based on these samples from the posterior. These ideas are illustrated on common statistic

  16. Bayesian statistics an introduction

    CERN Document Server

    Lee, Peter M

    2012-01-01

    Bayesian Statistics is the school of thought that combines prior beliefs with the likelihood of a hypothesis to arrive at posterior beliefs. The first edition of Peter Lee’s book appeared in 1989, but the subject has moved ever onwards, with increasing emphasis on Monte Carlo based techniques. This new fourth edition looks at recent techniques such as variational methods, Bayesian importance sampling, approximate Bayesian computation and Reversible Jump Markov Chain Monte Carlo (RJMCMC), providing a concise account of the way in which the Bayesian approach to statistics develops as wel

  17. Whole genome scan reveals the genetic signature of African Ankole cattle breed and potential for higher quality beef.

    Science.gov (United States)

    Taye, Mengistie; Kim, Jaemin; Yoon, Sook Hee; Lee, Wonseok; Hanotte, Olivier; Dessie, Tadelle; Kemp, Stephen; Mwai, Okeyo Ally; Caetano-Anolles, Kelsey; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

    2017-02-09

    identified are involved in muscle structure and metabolism, and adipose metabolism and adipogenesis. These genes help in the understanding of the biological mechanisms controlling beef quality characteristics in African Ankole cattle. These results provide a basis for further research on the genomic characteristics of Ankole and other Sanga cattle breeds for quality beef.

  18. Scanning the genome for gene SNPs related to climate adaptation and estimating selection at the molecular level in boreal black spruce.

    Science.gov (United States)

    Prunier, Julien; Laroche, Jérôme; Beaulieu, Jean; Bousquet, Jean

    2011-04-01

    Outlier detection methods were used to scan the genome of the boreal conifer black spruce (Picea mariana [Mill.] B.S.P.) for gene single-nucleotide polymorphisms (SNPs) potentially involved in adaptations to temperature and precipitation variations. The scan involved 583 SNPs from 313 genes potentially playing adaptive roles. Differentiation estimates among population groups defined following variation in temperature and precipitation were moderately high for adaptive quantitative characters such as the timing of budset or tree height (Q(ST) = 0.189-0.314). Average differentiation estimates for gene SNPs were null, with F(ST) values of 0.005 and 0.006, respectively, among temperature and precipitation population groups. Using two detection approaches, a total of 26 SNPs from 25 genes distributed among 11 of the 12 linkage groups of black spruce were detected as outliers with F(ST) as high as 0.078. Nearly half of the outlier SNPs were located in exons and half of those were nonsynonymous. The functional annotations of genes carrying outlier SNPs and regression analyses between the frequencies of these SNPs and climatic variables supported their implication in adaptive processes. Several genes carrying outlier SNPs belonged to gene families previously found to harbour outlier SNPs in a reproductively isolated but largely sympatric congeneric species, suggesting differential subfunctionalization of gene duplicates. Selection coefficient estimates (S) were moderate but well above the magnitude of drift (>1/N(e)), indicating that the signature of natural selection could be detected at the nucleotide level despite the recent establishment of these populations during the Holocene. © 2011 Blackwell Publishing Ltd.

  19. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  20. Bayesian Probability Theory

    Science.gov (United States)

    von der Linden, Wolfgang; Dose, Volker; von Toussaint, Udo

    2014-06-01

    Preface; Part I. Introduction: 1. The meaning of probability; 2. Basic definitions; 3. Bayesian inference; 4. Combinatrics; 5. Random walks; 6. Limit theorems; 7. Continuous distributions; 8. The central limit theorem; 9. Poisson processes and waiting times; Part II. Assigning Probabilities: 10. Transformation invariance; 11. Maximum entropy; 12. Qualified maximum entropy; 13. Global smoothness; Part III. Parameter Estimation: 14. Bayesian parameter estimation; 15. Frequentist parameter estimation; 16. The Cramer-Rao inequality; Part IV. Testing Hypotheses: 17. The Bayesian way; 18. The frequentist way; 19. Sampling distributions; 20. Bayesian vs frequentist hypothesis tests; Part V. Real World Applications: 21. Regression; 22. Inconsistent data; 23. Unrecognized signal contributions; 24. Change point problems; 25. Function estimation; 26. Integral equations; 27. Model selection; 28. Bayesian experimental design; Part VI. Probabilistic Numerical Techniques: 29. Numerical integration; 30. Monte Carlo methods; 31. Nested sampling; Appendixes; References; Index.

  1. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

    Science.gov (United States)

    Voruganti, V Saroja; Göring, Harald H H; Diego, Vincent P; Cai, Guowen; Mehta, Nitesh R; Haack, Karin; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2007-10-01

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

  2. A genome-wide admixture scan identifies MYH9 as a candidate locus associated with non-diabetic end stage renal disease in African Americans

    Science.gov (United States)

    Linda Kao, WH; Klag, Michael J; Meoni, Lucy A; Reich, David; Berthier-Schaad, Yvette; Li, Man; Coresh, Josef; Patterson, Nick; Tandon, Arti; Powe, Neil R; Fink, Nancy E; Sadler, John H; Weir, Matthew R; Abboud, Hanna E; Adler, Sharon; Divers, Jasmin; Iyengar, Sudha K; Freedman, Barry I; Kimmel, Paul L; Knowler, William C; Kohn, Orly F; Kramp, Kristopher; Leehey, David J; Nicholas, Susanne; Pahl, Madeleine; Schelling, Jeffrey R; Sedor, John R; Thornley-Brown, Denyse; Winkler, Cheryl A; Smith, Michael W.; Parekh, Rulan S.

    2008-01-01

    End stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans. This led to the hypothesis that susceptibility alleles for ESRD have a higher frequency in West African than European gene pool. We performed a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and demonstrated a highly significant association between excess African ancestry and non-diabetic ESRD (LOD 5.70) but not diabetic ESRD (LOD 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% credible interval 0.39 – 0.63) compared to African ancestry. Multiple common SNPs (allele frequency ranging from 0.2 to 0.6) in the gene that encodes non-muscle myosin heavy chain type II isoform A (MYH9) were associated with 2-4 times greater risk of non-diabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. PMID:18794854

  3. Konstruksi Bayesian Network Dengan Algoritma Bayesian Association Rule Mining Network

    OpenAIRE

    Octavian

    2015-01-01

    Beberapa tahun terakhir, Bayesian Network telah menjadi konsep yang populer digunakan dalam berbagai bidang kehidupan seperti dalam pengambilan sebuah keputusan dan menentukan peluang suatu kejadian dapat terjadi. Sayangnya, pengkonstruksian struktur dari Bayesian Network itu sendiri bukanlah hal yang sederhana. Oleh sebab itu, penelitian ini mencoba memperkenalkan algoritma Bayesian Association Rule Mining Network untuk memudahkan kita dalam mengkonstruksi Bayesian Network berdasarkan data ...

  4. Model Diagnostics for Bayesian Networks

    Science.gov (United States)

    Sinharay, Sandip

    2006-01-01

    Bayesian networks are frequently used in educational assessments primarily for learning about students' knowledge and skills. There is a lack of works on assessing fit of Bayesian networks. This article employs the posterior predictive model checking method, a popular Bayesian model checking tool, to assess fit of simple Bayesian networks. A…

  5. Bayesian data analysis for newcomers.

    Science.gov (United States)

    Kruschke, John K; Liddell, Torrin M

    2017-04-12

    This article explains the foundational concepts of Bayesian data analysis using virtually no mathematical notation. Bayesian ideas already match your intuitions from everyday reasoning and from traditional data analysis. Simple examples of Bayesian data analysis are presented that illustrate how the information delivered by a Bayesian analysis can be directly interpreted. Bayesian approaches to null-value assessment are discussed. The article clarifies misconceptions about Bayesian methods that newcomers might have acquired elsewhere. We discuss prior distributions and explain how they are not a liability but an important asset. We discuss the relation of Bayesian data analysis to Bayesian models of mind, and we briefly discuss what methodological problems Bayesian data analysis is not meant to solve. After you have read this article, you should have a clear sense of how Bayesian data analysis works and the sort of information it delivers, and why that information is so intuitive and useful for drawing conclusions from data.

  6. BAYESIAN BICLUSTERING FOR PATIENT STRATIFICATION.

    Science.gov (United States)

    Khakabimamaghani, Sahand; Ester, Martin

    2016-01-01

    The move from Empirical Medicine towards Personalized Medicine has attracted attention to Stratified Medicine (SM). Some methods are provided in the literature for patient stratification, which is the central task of SM, however, there are still significant open issues. First, it is still unclear if integrating different datatypes will help in detecting disease subtypes more accurately, and, if not, which datatype(s) are most useful for this task. Second, it is not clear how we can compare different methods of patient stratification. Third, as most of the proposed stratification methods are deterministic, there is a need for investigating the potential benefits of applying probabilistic methods. To address these issues, we introduce a novel integrative Bayesian biclustering method, called B2PS, for patient stratification and propose methods for evaluating the results. Our experimental results demonstrate the superiority of B2PS over a popular state-of-the-art method and the benefits of Bayesian approaches. Our results agree with the intuition that transcriptomic data forms a better basis for patient stratification than genomic data.

  7. Bayesian psychometric scaling

    NARCIS (Netherlands)

    Fox, G.J.A.; Berg, van den S.M.; Veldkamp, B.P.; Irwing, P.; Booth, T.; Hughes, D.

    2015-01-01

    In educational and psychological studies, psychometric methods are involved in the measurement of constructs, and in constructing and validating measurement instruments. Assessment results are typically used to measure student proficiency levels and test characteristics. Recently, Bayesian item resp

  8. Bayesian psychometric scaling

    NARCIS (Netherlands)

    Fox, Gerardus J.A.; van den Berg, Stéphanie Martine; Veldkamp, Bernard P.; Irwing, P.; Booth, T.; Hughes, D.

    2015-01-01

    In educational and psychological studies, psychometric methods are involved in the measurement of constructs, and in constructing and validating measurement instruments. Assessment results are typically used to measure student proficiency levels and test characteristics. Recently, Bayesian item

  9. Practical Bayesian Tomography

    CERN Document Server

    Granade, Christopher; Cory, D G

    2015-01-01

    In recent years, Bayesian methods have been proposed as a solution to a wide range of issues in quantum state and process tomography. State-of- the-art Bayesian tomography solutions suffer from three problems: numerical intractability, a lack of informative prior distributions, and an inability to track time-dependent processes. Here, we solve all three problems. First, we use modern statistical methods, as pioneered by Husz\\'ar and Houlsby and by Ferrie, to make Bayesian tomography numerically tractable. Our approach allows for practical computation of Bayesian point and region estimators for quantum states and channels. Second, we propose the first informative priors on quantum states and channels. Finally, we develop a method that allows online tracking of time-dependent states and estimates the drift and diffusion processes affecting a state. We provide source code and animated visual examples for our methods.

  10. Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22.

    Science.gov (United States)

    Pulli, K; Karma, K; Norio, R; Sistonen, P; Göring, H H H; Järvelä, I

    2008-07-01

    Music perception and performance are comprehensive human cognitive functions and thus provide an excellent model system for studying human behaviour and brain function. However, the molecules involved in mediating music perception and performance are so far uncharacterised. To unravel the biological background of music perception, using molecular and statistical genetic approaches. 15 Finnish multigenerational families (with a total of 234 family members) were recruited via a nationwide search. The phenotype of all family members was determined using three tests used in defining musical aptitude: a test for auditory structuring ability (Karma Music test; KMT) commonly used in Finland, and the Seashore pitch and time discrimination subtests (SP and ST respectively) used internationally. We calculated heritabilities and performed a genome-wide variance components-based linkage scan using genotype data for 1113 microsatellite markers. The heritability estimates were 42% for KMT, 57% for SP, 21% for ST and 48% for the combined music test scores. Significant evidence of linkage was obtained on chromosome 4q22 (LOD 3.33) and suggestive evidence of linkage at 8q13-21 (LOD 2.29) with the combined music test scores, using variance component linkage analyses. The major contribution of the 4q22 locus was obtained for the KMT (LOD 2.91). Interestingly, a positive LOD score of 1.69 was shown at 18q, a region previously linked to dyslexia (DYX6) using combined music test scores. Our results show that there is a genetic contribution to musical aptitude that is likely to be regulated by several predisposing genes or variants.

  11. Genome scan for loci predisposing to anxiety disorders using a novel multivariate approach: strong evidence for a chromosome 4 risk locus.

    Science.gov (United States)

    Kaabi, Belhassen; Gelernter, Joel; Woods, Scott W; Goddard, Andrew; Page, Grier P; Elston, Robert C

    2006-04-01

    We conducted a 10-centimorgan linkage autosomal genome scan in a set of 19 extended American pedigrees (219 subjects) ascertained through probands with panic disorder. Several anxiety disorders--including social phobia, agoraphobia, and simple phobia--in addition to panic disorder segregate in these families. In previous studies of this sample, linkage analyses were based separately on each of the individual categorical affection diagnoses. Given the substantial comorbidity between anxiety disorders and their probable shared genetic liability, it is clear that this method discards a considerable amount of information. In this article, we propose a new approach that considers panic disorder, simple phobia, social phobia, and agoraphobia as expressions of the same multivariate, putatively genetically influenced trait. We applied the most powerful multipoint Haseman-Elston method, using the grade of membership score generated from a fuzzy clustering of these phenotypes as the dependent variable in Haseman-Elston regression. One region on chromosome 4q31-q34, at marker D4S413 (with multipoint and single-point nominal P values < .00001), showed strong evidence of linkage (genomewide significance at P<.05). The same region is known to be the site of a neuropeptide Y receptor gene, NPY1R (4q31-q32), that was recently connected to anxiolytic-like effects in rats. Several other regions on four chromosomes (4q21.21-22.3, 5q14.2-14.3, 8p23.1, and 14q22.3-23.3) met criteria for suggestive linkage (multipoint nominal P values < .01). Family-by-family analysis did not show any strong evidence of heterogeneity. Our findings support the notion that the major anxiety disorders, including phobias and panic disorder, are complex traits that share at least one susceptibility locus. This method could be applied to other complex traits for which shared genetic-liability factors are thought to be important, such as substance dependencies.

  12. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  13. Bayesian Face Sketch Synthesis.

    Science.gov (United States)

    Wang, Nannan; Gao, Xinbo; Sun, Leiyu; Li, Jie

    2017-03-01

    Exemplar-based face sketch synthesis has been widely applied to both digital entertainment and law enforcement. In this paper, we propose a Bayesian framework for face sketch synthesis, which provides a systematic interpretation for understanding the common properties and intrinsic difference in different methods from the perspective of probabilistic graphical models. The proposed Bayesian framework consists of two parts: the neighbor selection model and the weight computation model. Within the proposed framework, we further propose a Bayesian face sketch synthesis method. The essential rationale behind the proposed Bayesian method is that we take the spatial neighboring constraint between adjacent image patches into consideration for both aforementioned models, while the state-of-the-art methods neglect the constraint either in the neighbor selection model or in the weight computation model. Extensive experiments on the Chinese University of Hong Kong face sketch database demonstrate that the proposed Bayesian method could achieve superior performance compared with the state-of-the-art methods in terms of both subjective perceptions and objective evaluations.

  14. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  15. Bayesian Visual Odometry

    Science.gov (United States)

    Center, Julian L.; Knuth, Kevin H.

    2011-03-01

    Visual odometry refers to tracking the motion of a body using an onboard vision system. Practical visual odometry systems combine the complementary accuracy characteristics of vision and inertial measurement units. The Mars Exploration Rovers, Spirit and Opportunity, used this type of visual odometry. The visual odometry algorithms in Spirit and Opportunity were based on Bayesian methods, but a number of simplifying approximations were needed to deal with onboard computer limitations. Furthermore, the allowable motion of the rover had to be severely limited so that computations could keep up. Recent advances in computer technology make it feasible to implement a fully Bayesian approach to visual odometry. This approach combines dense stereo vision, dense optical flow, and inertial measurements. As with all true Bayesian methods, it also determines error bars for all estimates. This approach also offers the possibility of using Micro-Electro Mechanical Systems (MEMS) inertial components, which are more economical, weigh less, and consume less power than conventional inertial components.

  16. Hybrid Batch Bayesian Optimization

    CERN Document Server

    Azimi, Javad; Fern, Xiaoli

    2012-01-01

    Bayesian Optimization aims at optimizing an unknown non-convex/concave function that is costly to evaluate. We are interested in application scenarios where concurrent function evaluations are possible. Under such a setting, BO could choose to either sequentially evaluate the function, one input at a time and wait for the output of the function before making the next selection, or evaluate the function at a batch of multiple inputs at once. These two different settings are commonly referred to as the sequential and batch settings of Bayesian Optimization. In general, the sequential setting leads to better optimization performance as each function evaluation is selected with more information, whereas the batch setting has an advantage in terms of the total experimental time (the number of iterations). In this work, our goal is to combine the strength of both settings. Specifically, we systematically analyze Bayesian optimization using Gaussian process as the posterior estimator and provide a hybrid algorithm t...

  17. Bayesian least squares deconvolution

    Science.gov (United States)

    Asensio Ramos, A.; Petit, P.

    2015-11-01

    Aims: We develop a fully Bayesian least squares deconvolution (LSD) that can be applied to the reliable detection of magnetic signals in noise-limited stellar spectropolarimetric observations using multiline techniques. Methods: We consider LSD under the Bayesian framework and we introduce a flexible Gaussian process (GP) prior for the LSD profile. This prior allows the result to automatically adapt to the presence of signal. We exploit several linear algebra identities to accelerate the calculations. The final algorithm can deal with thousands of spectral lines in a few seconds. Results: We demonstrate the reliability of the method with synthetic experiments and we apply it to real spectropolarimetric observations of magnetic stars. We are able to recover the magnetic signals using a small number of spectral lines, together with the uncertainty at each velocity bin. This allows the user to consider if the detected signal is reliable. The code to compute the Bayesian LSD profile is freely available.

  18. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.;

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corr......This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  19. Bayesian least squares deconvolution

    CERN Document Server

    Ramos, A Asensio

    2015-01-01

    Aims. To develop a fully Bayesian least squares deconvolution (LSD) that can be applied to the reliable detection of magnetic signals in noise-limited stellar spectropolarimetric observations using multiline techniques. Methods. We consider LSD under the Bayesian framework and we introduce a flexible Gaussian Process (GP) prior for the LSD profile. This prior allows the result to automatically adapt to the presence of signal. We exploit several linear algebra identities to accelerate the calculations. The final algorithm can deal with thousands of spectral lines in a few seconds. Results. We demonstrate the reliability of the method with synthetic experiments and we apply it to real spectropolarimetric observations of magnetic stars. We are able to recover the magnetic signals using a small number of spectral lines, together with the uncertainty at each velocity bin. This allows the user to consider if the detected signal is reliable. The code to compute the Bayesian LSD profile is freely available.

  20. Bayesian peak picking for NMR spectra.

    Science.gov (United States)

    Cheng, Yichen; Gao, Xin; Liang, Faming

    2014-02-01

    Protein structure determination is a very important topic in structural genomics, which helps people to understand varieties of biological functions such as protein-protein interactions, protein-DNA interactions and so on. Nowadays, nuclear magnetic resonance (NMR) has often been used to determine the three-dimensional structures of protein in vivo. This study aims to automate the peak picking step, the most important and tricky step in NMR structure determination. We propose to model the NMR spectrum by a mixture of bivariate Gaussian densities and use the stochastic approximation Monte Carlo algorithm as the computational tool to solve the problem. Under the Bayesian framework, the peak picking problem is casted as a variable selection problem. The proposed method can automatically distinguish true peaks from false ones without preprocessing the data. To the best of our knowledge, this is the first effort in the literature that tackles the peak picking problem for NMR spectrum data using Bayesian method.

  1. Bayesian Peak Picking for NMR Spectra

    KAUST Repository

    Cheng, Yichen

    2014-02-01

    Protein structure determination is a very important topic in structural genomics, which helps people to understand varieties of biological functions such as protein-protein interactions, protein–DNA interactions and so on. Nowadays, nuclear magnetic resonance (NMR) has often been used to determine the three-dimensional structures of protein in vivo. This study aims to automate the peak picking step, the most important and tricky step in NMR structure determination. We propose to model the NMR spectrum by a mixture of bivariate Gaussian densities and use the stochastic approximation Monte Carlo algorithm as the computational tool to solve the problem. Under the Bayesian framework, the peak picking problem is casted as a variable selection problem. The proposed method can automatically distinguish true peaks from false ones without preprocessing the data. To the best of our knowledge, this is the first effort in the literature that tackles the peak picking problem for NMR spectrum data using Bayesian method.

  2. Probabilistic Inferences in Bayesian Networks

    OpenAIRE

    Ding, Jianguo

    2010-01-01

    This chapter summarizes the popular inferences methods in Bayesian networks. The results demonstrates that the evidence can propagated across the Bayesian networks by any links, whatever it is forward or backward or intercausal style. The belief updating of Bayesian networks can be obtained by various available inference techniques. Theoretically, exact inferences in Bayesian networks is feasible and manageable. However, the computing and inference is NP-hard. That means, in applications, in ...

  3. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  4. Bayesian methods for hackers probabilistic programming and Bayesian inference

    CERN Document Server

    Davidson-Pilon, Cameron

    2016-01-01

    Bayesian methods of inference are deeply natural and extremely powerful. However, most discussions of Bayesian inference rely on intensely complex mathematical analyses and artificial examples, making it inaccessible to anyone without a strong mathematical background. Now, though, Cameron Davidson-Pilon introduces Bayesian inference from a computational perspective, bridging theory to practice–freeing you to get results using computing power. Bayesian Methods for Hackers illuminates Bayesian inference through probabilistic programming with the powerful PyMC language and the closely related Python tools NumPy, SciPy, and Matplotlib. Using this approach, you can reach effective solutions in small increments, without extensive mathematical intervention. Davidson-Pilon begins by introducing the concepts underlying Bayesian inference, comparing it with other techniques and guiding you through building and training your first Bayesian model. Next, he introduces PyMC through a series of detailed examples a...

  5. The Bayesian Inventory Problem

    Science.gov (United States)

    1984-05-01

    Bayesian Approach to Demand Estimation and Inventory Provisioning," Naval Research Logistics Quarterly. Vol 20, 1973, (p607-624). 4 DeGroot , Morris H...page is blank APPENDIX A SUFFICIENT STATISTICS A convenient reference for moat of this material is DeGroot (41. Su-pose that we are sampling from a

  6. Probability and Bayesian statistics

    CERN Document Server

    1987-01-01

    This book contains selected and refereed contributions to the "Inter­ national Symposium on Probability and Bayesian Statistics" which was orga­ nized to celebrate the 80th birthday of Professor Bruno de Finetti at his birthplace Innsbruck in Austria. Since Professor de Finetti died in 1985 the symposium was dedicated to the memory of Bruno de Finetti and took place at Igls near Innsbruck from 23 to 26 September 1986. Some of the pa­ pers are published especially by the relationship to Bruno de Finetti's scientific work. The evolution of stochastics shows growing importance of probability as coherent assessment of numerical values as degrees of believe in certain events. This is the basis for Bayesian inference in the sense of modern statistics. The contributions in this volume cover a broad spectrum ranging from foundations of probability across psychological aspects of formulating sub­ jective probability statements, abstract measure theoretical considerations, contributions to theoretical statistics an...

  7. Bayesian community detection

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel N

    2012-01-01

    Many networks of scientific interest naturally decompose into clusters or communities with comparatively fewer external than internal links; however, current Bayesian models of network communities do not exert this intuitive notion of communities. We formulate a nonparametric Bayesian model...... for community detection consistent with an intuitive definition of communities and present a Markov chain Monte Carlo procedure for inferring the community structure. A Matlab toolbox with the proposed inference procedure is available for download. On synthetic and real networks, our model detects communities...... consistent with ground truth, and on real networks, it outperforms existing approaches in predicting missing links. This suggests that community structure is an important structural property of networks that should be explicitly modeled....

  8. Introduction to Bayesian statistics

    CERN Document Server

    Koch, Karl-Rudolf

    2007-01-01

    This book presents Bayes' theorem, the estimation of unknown parameters, the determination of confidence regions and the derivation of tests of hypotheses for the unknown parameters. It does so in a simple manner that is easy to comprehend. The book compares traditional and Bayesian methods with the rules of probability presented in a logical way allowing an intuitive understanding of random variables and their probability distributions to be formed.

  9. Bayesian Watermark Attacks

    OpenAIRE

    Shterev, Ivo; Dunson, David

    2012-01-01

    This paper presents an application of statistical machine learning to the field of watermarking. We propose a new attack model on additive spread-spectrum watermarking systems. The proposed attack is based on Bayesian statistics. We consider the scenario in which a watermark signal is repeatedly embedded in specific, possibly chosen based on a secret message bitstream, segments (signals) of the host data. The host signal can represent a patch of pixels from an image or a video frame. We propo...

  10. Subjective Bayesian Beliefs

    DEFF Research Database (Denmark)

    Antoniou, Constantinos; Harrison, Glenn W.; Lau, Morten I.

    2015-01-01

    A large literature suggests that many individuals do not apply Bayes’ Rule when making decisions that depend on them correctly pooling prior information and sample data. We replicate and extend a classic experimental study of Bayesian updating from psychology, employing the methods of experimental...... economics, with careful controls for the confounding effects of risk aversion. Our results show that risk aversion significantly alters inferences on deviations from Bayes’ Rule....

  11. Reduced Bayesian Inversion

    OpenAIRE

    Himpe, Christian; Ohlberger, Mario

    2014-01-01

    Bayesian inversion of models with large state and parameter spaces proves to be computationally complex. A combined state and parameter reduction can significantly decrease the computational time and cost required for the parameter estimation. The presented technique is based on the well-known balanced truncation approach. Classically, the balancing of the controllability and observability gramians allows a truncation of discardable states. Here the underlying model, being a linear or nonline...

  12. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...... in a Matlab toolbox, is demonstrated for non-negative decompositions and compared with non-negative matrix factorization....

  13. Bayesian theory and applications

    CERN Document Server

    Dellaportas, Petros; Polson, Nicholas G; Stephens, David A

    2013-01-01

    The development of hierarchical models and Markov chain Monte Carlo (MCMC) techniques forms one of the most profound advances in Bayesian analysis since the 1970s and provides the basis for advances in virtually all areas of applied and theoretical Bayesian statistics. This volume guides the reader along a statistical journey that begins with the basic structure of Bayesian theory, and then provides details on most of the past and present advances in this field. The book has a unique format. There is an explanatory chapter devoted to each conceptual advance followed by journal-style chapters that provide applications or further advances on the concept. Thus, the volume is both a textbook and a compendium of papers covering a vast range of topics. It is appropriate for a well-informed novice interested in understanding the basic approach, methods and recent applications. Because of its advanced chapters and recent work, it is also appropriate for a more mature reader interested in recent applications and devel...

  14. SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm, efficiently reveals the risk genetic epistasis in bipolar disorder

    Institute of Scientific and Technical Information of China (English)

    Xiaohan Hu; Qiang Liu; Zhao Zhang; Zhiqiang Li; Shilin Wang; Lin He; Yongyong Shi

    2010-01-01

    @@ Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study (GWAS) of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium's (WTCCC)GWAS data of bipolar disorder (BPD) with 500K SNPs.

  15. The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J × SM/J murine model.

    Science.gov (United States)

    Lawson, Heather A; Lee, Arthur; Fawcett, Gloria L; Wang, Bing; Pletscher, L Susan; Maxwell, Taylor J; Ehrich, Thomas H; Kenney-Hunt, Jane P; Wolf, Jason B; Semenkovich, Clay F; Cheverud, James M

    2011-04-01

    Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F(16) Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. We found that different cohorts often have unique genetic effects at the same loci, and that genetic signals can be masked or erroneously assigned to specific cohorts if they are not considered individually. Our data demonstrate that the effects of genes on complex trait variation are highly context-dependent and that the same genomic sequence can affect traits differently depending on an individual's sex and/or dietary environment. Our results have important implications for studies of complex traits in humans.

  16. A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32.

    Science.gov (United States)

    Gonzalez, Suzanne; Camarillo, Cynthia; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Almasy, Laura; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2014-09-01

    A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. © 2014 Wiley Periodicals, Inc.

  17. Genome scans reveal candidate domestication and improvement genes in cultivated sunflower, as well as post-domestication introgression with wild relatives.

    Science.gov (United States)

    Baute, Gregory J; Kane, Nolan C; Grassa, Christopher J; Lai, Zhao; Rieseberg, Loren H

    2015-04-01

    The development of modern crops typically involves both selection and hybridization, but to date most studies have focused on the former. In the present study, we explore how both processes, and their interactions, have molded the genome of the cultivated sunflower (Helianthus annuus), a globally important oilseed. To identify genes targeted by selection during the domestication and improvement of sunflower, and to detect post-domestication hybridization with wild species, we analyzed transcriptome sequences of 80 genotypes, including wild, landrace, and modern lines of H. annuus, as well as two cross-compatible wild relatives, Helianthus argophyllus and Helianthus petiolaris. Outlier analyses identified 122 and 15 candidate genes associated with domestication and improvement, respectively. As in several previous studies, genes putatively involved in oil biosynthesis were the most extreme outliers. Additionally, several promising associations were observed with previously mapped quantitative trait loci (QTLs), such as branching. Admixture analyses revealed that all the modern cultivar genomes we examined contained one or more introgressions from wild populations, with every chromosome having evidence of introgression in at least one modern line. Cumulatively, introgressions cover c. 10% of the cultivated sunflower genome. Surprisingly, introgressions do not avoid candidate domestication genes, probably because of the reintroduction of branching.

  18. A Bayesian variable selection procedure for ranking overlapping gene sets

    DEFF Research Database (Denmark)

    Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

    2012-01-01

    described. In many cases, these methods test one gene set at a time, and therefore do not consider overlaps among the pathways. Here, we present a Bayesian variable selection method to prioritize gene sets that overcomes this limitation by considering all gene sets simultaneously. We applied Bayesian...... variable selection to differential expression to prioritize the molecular and genetic pathways involved in the responses to Escherichia coli infection in Danish Holstein cows. Results We used a Bayesian variable selection method to prioritize Kyoto Encyclopedia of Genes and Genomes pathways. We used our...... data to study how the variable selection method was affected by overlaps among the pathways. In addition, we compared our approach to another that ignores the overlaps, and studied the differences in the prioritization. The variable selection method was robust to a change in prior probability...

  19. Bayesian nonparametric data analysis

    CERN Document Server

    Müller, Peter; Jara, Alejandro; Hanson, Tim

    2015-01-01

    This book reviews nonparametric Bayesian methods and models that have proven useful in the context of data analysis. Rather than providing an encyclopedic review of probability models, the book’s structure follows a data analysis perspective. As such, the chapters are organized by traditional data analysis problems. In selecting specific nonparametric models, simpler and more traditional models are favored over specialized ones. The discussed methods are illustrated with a wealth of examples, including applications ranging from stylized examples to case studies from recent literature. The book also includes an extensive discussion of computational methods and details on their implementation. R code for many examples is included in on-line software pages.

  20. Applied Bayesian modelling

    CERN Document Server

    Congdon, Peter

    2014-01-01

    This book provides an accessible approach to Bayesian computing and data analysis, with an emphasis on the interpretation of real data sets. Following in the tradition of the successful first edition, this book aims to make a wide range of statistical modeling applications accessible using tested code that can be readily adapted to the reader's own applications. The second edition has been thoroughly reworked and updated to take account of advances in the field. A new set of worked examples is included. The novel aspect of the first edition was the coverage of statistical modeling using WinBU

  1. Bayesian grid matching

    DEFF Research Database (Denmark)

    Hartelius, Karsten; Carstensen, Jens Michael

    2003-01-01

    A method for locating distorted grid structures in images is presented. The method is based on the theories of template matching and Bayesian image restoration. The grid is modeled as a deformable template. Prior knowledge of the grid is described through a Markov random field (MRF) model which...... nodes and the arc prior models variations in row and column spacing across the grid. Grid matching is done by placing an initial rough grid over the image and applying an ensemble annealing scheme to maximize the posterior distribution of the grid. The method can be applied to noisy images with missing...

  2. Bayesian Approach for Inconsistent Information.

    Science.gov (United States)

    Stein, M; Beer, M; Kreinovich, V

    2013-10-01

    In engineering situations, we usually have a large amount of prior knowledge that needs to be taken into account when processing data. Traditionally, the Bayesian approach is used to process data in the presence of prior knowledge. Sometimes, when we apply the traditional Bayesian techniques to engineering data, we get inconsistencies between the data and prior knowledge. These inconsistencies are usually caused by the fact that in the traditional approach, we assume that we know the exact sample values, that the prior distribution is exactly known, etc. In reality, the data is imprecise due to measurement errors, the prior knowledge is only approximately known, etc. So, a natural way to deal with the seemingly inconsistent information is to take this imprecision into account in the Bayesian approach - e.g., by using fuzzy techniques. In this paper, we describe several possible scenarios for fuzzifying the Bayesian approach. Particular attention is paid to the interaction between the estimated imprecise parameters. In this paper, to implement the corresponding fuzzy versions of the Bayesian formulas, we use straightforward computations of the related expression - which makes our computations reasonably time-consuming. Computations in the traditional (non-fuzzy) Bayesian approach are much faster - because they use algorithmically efficient reformulations of the Bayesian formulas. We expect that similar reformulations of the fuzzy Bayesian formulas will also drastically decrease the computation time and thus, enhance the practical use of the proposed methods.

  3. Classification using Bayesian neural nets

    NARCIS (Netherlands)

    J.C. Bioch (Cor); O. van der Meer; R. Potharst (Rob)

    1995-01-01

    textabstractRecently, Bayesian methods have been proposed for neural networks to solve regression and classification problems. These methods claim to overcome some difficulties encountered in the standard approach such as overfitting. However, an implementation of the full Bayesian approach to neura

  4. Inference in hybrid Bayesian networks

    DEFF Research Database (Denmark)

    Lanseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2009-01-01

    Since the 1980s, Bayesian Networks (BNs) have become increasingly popular for building statistical models of complex systems. This is particularly true for boolean systems, where BNs often prove to be a more efficient modelling framework than traditional reliability-techniques (like fault trees...... decade's research on inference in hybrid Bayesian networks. The discussions are linked to an example model for estimating human reliability....

  5. Interactive Instruction in Bayesian Inference

    DEFF Research Database (Denmark)

    Khan, Azam; Breslav, Simon; Hornbæk, Kasper

    2017-01-01

    An instructional approach is presented to improve human performance in solving Bayesian inference problems. Starting from the original text of the classic Mammography Problem, the textual expression is modified and visualizations are added according to Mayer’s principles of instruction...... that an instructional approach to improving human performance in Bayesian inference is a promising direction....

  6. Bayesian Intersubjectivity and Quantum Theory

    Science.gov (United States)

    Pérez-Suárez, Marcos; Santos, David J.

    2005-02-01

    Two of the major approaches to probability, namely, frequentism and (subjectivistic) Bayesian theory, are discussed, together with the replacement of frequentist objectivity for Bayesian intersubjectivity. This discussion is then expanded to Quantum Theory, as quantum states and operations can be seen as structural elements of a subjective nature.

  7. Bayesian inference with ecological applications

    CERN Document Server

    Link, William A

    2009-01-01

    This text is written to provide a mathematically sound but accessible and engaging introduction to Bayesian inference specifically for environmental scientists, ecologists and wildlife biologists. It emphasizes the power and usefulness of Bayesian methods in an ecological context. The advent of fast personal computers and easily available software has simplified the use of Bayesian and hierarchical models . One obstacle remains for ecologists and wildlife biologists, namely the near absence of Bayesian texts written specifically for them. The book includes many relevant examples, is supported by software and examples on a companion website and will become an essential grounding in this approach for students and research ecologists. Engagingly written text specifically designed to demystify a complex subject Examples drawn from ecology and wildlife research An essential grounding for graduate and research ecologists in the increasingly prevalent Bayesian approach to inference Companion website with analyt...

  8. Bayesian Inference on Gravitational Waves

    Directory of Open Access Journals (Sweden)

    Asad Ali

    2015-12-01

    Full Text Available The Bayesian approach is increasingly becoming popular among the astrophysics data analysis communities. However, the Pakistan statistics communities are unaware of this fertile interaction between the two disciplines. Bayesian methods have been in use to address astronomical problems since the very birth of the Bayes probability in eighteenth century. Today the Bayesian methods for the detection and parameter estimation of gravitational waves have solid theoretical grounds with a strong promise for the realistic applications. This article aims to introduce the Pakistan statistics communities to the applications of Bayesian Monte Carlo methods in the analysis of gravitational wave data with an  overview of the Bayesian signal detection and estimation methods and demonstration by a couple of simplified examples.

  9. Approximate Bayesian computation.

    Directory of Open Access Journals (Sweden)

    Mikael Sunnåker

    Full Text Available Approximate Bayesian computation (ABC constitutes a class of computational methods rooted in Bayesian statistics. In all model-based statistical inference, the likelihood function is of central importance, since it expresses the probability of the observed data under a particular statistical model, and thus quantifies the support data lend to particular values of parameters and to choices among different models. For simple models, an analytical formula for the likelihood function can typically be derived. However, for more complex models, an analytical formula might be elusive or the likelihood function might be computationally very costly to evaluate. ABC methods bypass the evaluation of the likelihood function. In this way, ABC methods widen the realm of models for which statistical inference can be considered. ABC methods are mathematically well-founded, but they inevitably make assumptions and approximations whose impact needs to be carefully assessed. Furthermore, the wider application domain of ABC exacerbates the challenges of parameter estimation and model selection. ABC has rapidly gained popularity over the last years and in particular for the analysis of complex problems arising in biological sciences (e.g., in population genetics, ecology, epidemiology, and systems biology.

  10. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.

    Directory of Open Access Journals (Sweden)

    Matthew P Johnson

    Full Text Available Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7, OR = 1.57; rs12711941, p = 4.26×10(-7, OR = 1.56 satisfied our genome-wide significance threshold (modified Bonferroni p0.92. We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03. We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s.

  11. A Bayesian variable selection procedure to rank overlapping gene sets

    Directory of Open Access Journals (Sweden)

    Skarman Axel

    2012-05-01

    Full Text Available Abstract Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been described. In many cases, these methods test one gene set at a time, and therefore do not consider overlaps among the pathways. Here, we present a Bayesian variable selection method to prioritize gene sets that overcomes this limitation by considering all gene sets simultaneously. We applied Bayesian variable selection to differential expression to prioritize the molecular and genetic pathways involved in the responses to Escherichia coli infection in Danish Holstein cows. Results We used a Bayesian variable selection method to prioritize Kyoto Encyclopedia of Genes and Genomes pathways. We used our data to study how the variable selection method was affected by overlaps among the pathways. In addition, we compared our approach to another that ignores the overlaps, and studied the differences in the prioritization. The variable selection method was robust to a change in prior probability and stable given a limited number of observations. Conclusions Bayesian variable selection is a useful way to prioritize gene sets while considering their overlaps. Ignoring the overlaps gives different and possibly misleading results. Additional procedures may be needed in cases of highly overlapping pathways that are hard to prioritize.

  12. MRI Scans

    Science.gov (United States)

    Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from ...

  13. Bayesian cloud detection for MERIS, AATSR, and their combination

    Directory of Open Access Journals (Sweden)

    A. Hollstein

    2014-11-01

    Full Text Available A broad range of different of Bayesian cloud detection schemes is applied to measurements from the Medium Resolution Imaging Spectrometer (MERIS, the Advanced Along-Track Scanning Radiometer (AATSR, and their combination. The cloud masks were designed to be numerically efficient and suited for the processing of large amounts of data. Results from the classical and naive approach to Bayesian cloud masking are discussed for MERIS and AATSR as well as for their combination. A sensitivity study on the resolution of multidimensional histograms, which were post-processed by Gaussian smoothing, shows how theoretically insufficient amounts of truth data can be used to set up accurate classical Bayesian cloud masks. Sets of exploited features from single and derived channels are numerically optimized and results for naive and classical Bayesian cloud masks are presented. The application of the Bayesian approach is discussed in terms of reproducing existing algorithms, enhancing existing algorithms, increasing the robustness of existing algorithms, and on setting up new classification schemes based on manually classified scenes.

  14. How to practise Bayesian statistics outside the Bayesian church: What philosophy for Bayesian statistical modelling?

    NARCIS (Netherlands)

    Borsboom, D.; Haig, B.D.

    2013-01-01

    Unlike most other statistical frameworks, Bayesian statistical inference is wedded to a particular approach in the philosophy of science (see Howson & Urbach, 2006); this approach is called Bayesianism. Rather than being concerned with model fitting, this position in the philosophy of science primar

  15. Implementing Bayesian Vector Autoregressions Implementing Bayesian Vector Autoregressions

    Directory of Open Access Journals (Sweden)

    Richard M. Todd

    1988-03-01

    Full Text Available Implementing Bayesian Vector Autoregressions This paper discusses how the Bayesian approach can be used to construct a type of multivariate forecasting model known as a Bayesian vector autoregression (BVAR. In doing so, we mainly explain Doan, Littermann, and Sims (1984 propositions on how to estimate a BVAR based on a certain family of prior probability distributions. indexed by a fairly small set of hyperparameters. There is also a discussion on how to specify a BVAR and set up a BVAR database. A 4-variable model is used to iliustrate the BVAR approach.

  16. Bayesian inference in geomagnetism

    Science.gov (United States)

    Backus, George E.

    1988-01-01

    The inverse problem in empirical geomagnetic modeling is investigated, with critical examination of recently published studies. Particular attention is given to the use of Bayesian inference (BI) to select the damping parameter lambda in the uniqueness portion of the inverse problem. The mathematical bases of BI and stochastic inversion are explored, with consideration of bound-softening problems and resolution in linear Gaussian BI. The problem of estimating the radial magnetic field B(r) at the earth core-mantle boundary from surface and satellite measurements is then analyzed in detail, with specific attention to the selection of lambda in the studies of Gubbins (1983) and Gubbins and Bloxham (1985). It is argued that the selection method is inappropriate and leads to lambda values much larger than those that would result if a reasonable bound on the heat flow at the CMB were assumed.

  17. Bayesian Geostatistical Design

    DEFF Research Database (Denmark)

    Diggle, Peter; Lophaven, Søren Nymand

    2006-01-01

    This paper describes the use of model-based geostatistics for choosing the set of sampling locations, collectively called the design, to be used in a geostatistical analysis. Two types of design situation are considered. These are retrospective design, which concerns the addition of sampling...... locations to, or deletion of locations from, an existing design, and prospective design, which consists of choosing positions for a new set of sampling locations. We propose a Bayesian design criterion which focuses on the goal of efficient spatial prediction whilst allowing for the fact that model...... parameter values are unknown. The results show that in this situation a wide range of interpoint distances should be included in the design, and the widely used regular design is often not the best choice....

  18. Bayesian Rose Trees

    CERN Document Server

    Blundell, Charles; Heller, Katherine A

    2012-01-01

    Hierarchical structure is ubiquitous in data across many domains. There are many hier- archical clustering methods, frequently used by domain experts, which strive to discover this structure. However, most of these meth- ods limit discoverable hierarchies to those with binary branching structure. This lim- itation, while computationally convenient, is often undesirable. In this paper we ex- plore a Bayesian hierarchical clustering algo- rithm that can produce trees with arbitrary branching structure at each node, known as rose trees. We interpret these trees as mixtures over partitions of a data set, and use a computationally efficient, greedy ag- glomerative algorithm to find the rose trees which have high marginal likelihood given the data. Lastly, we perform experiments which demonstrate that rose trees are better models of data than the typical binary trees returned by other hierarchical clustering algorithms.

  19. Bayesian Causal Induction

    CERN Document Server

    Ortega, Pedro A

    2011-01-01

    Discovering causal relationships is a hard task, often hindered by the need for intervention, and often requiring large amounts of data to resolve statistical uncertainty. However, humans quickly arrive at useful causal relationships. One possible reason is that humans use strong prior knowledge; and rather than encoding hard causal relationships, they encode beliefs over causal structures, allowing for sound generalization from the observations they obtain from directly acting in the world. In this work we propose a Bayesian approach to causal induction which allows modeling beliefs over multiple causal hypotheses and predicting the behavior of the world under causal interventions. We then illustrate how this method extracts causal information from data containing interventions and observations.

  20. Book review: Bayesian analysis for population ecology

    Science.gov (United States)

    Link, William A.

    2011-01-01

    Brian Dennis described the field of ecology as “fertile, uncolonized ground for Bayesian ideas.” He continued: “The Bayesian propagule has arrived at the shore. Ecologists need to think long and hard about the consequences of a Bayesian ecology. The Bayesian outlook is a successful competitor, but is it a weed? I think so.” (Dennis 2004)

  1. Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study.

    Directory of Open Access Journals (Sweden)

    Dharambir K Sanghera

    Full Text Available In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, very low-density lipoprotein (VLDL cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS. A total of 870 individuals (526 male/344 female from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using S(all statistics (implemented in Merlin did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011 occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016 and 5p15.33 (p = 0.0031 and for LDL cholesterol at 10p11.23 (p = 0.0045. Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance.

  2. Bayesian adaptive methods for clinical trials

    CERN Document Server

    Berry, Scott M; Muller, Peter

    2010-01-01

    Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, Bayesian Adaptive Methods for Clinical Trials explores the growing role of Bayesian thinking in the rapidly changing world of clinical trial analysis. The book first summarizes the current state of clinical trial design and analysis and introduces the main ideas and potential benefits of a Bayesian alternative. It then gives an overview of basic Bayesian methodological and computational tools needed for Bayesian clinical trials. With a focus on Bayesian designs that achieve good power and Type I error, the next chapters present Bayesian tools useful in early (Phase I) and middle (Phase II) clinical trials as well as two recent Bayesian adaptive Phase II studies: the BATTLE and ISP...

  3. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

    Directory of Open Access Journals (Sweden)

    Fu-Hui Xiao

    Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

  4. Genome-wide scan identifies variant in TNFSF13 associated with serum IgM in a healthy Chinese male population.

    Directory of Open Access Journals (Sweden)

    Ming Yang

    Full Text Available IgM provides a first line of defense during microbial infections. Serum IgM levels are detected routinely in clinical practice. And IgM is a genetically complex trait. We conducted a two-stage genome-wide association study (GWAS to identify genetic variants affecting serum IgM levels in a Chinese population of 3495, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Our data show that a common single nucleotide polymorphism (SNP, rs11552708 located in the TNFSF13 gene was significantly associated with IgM levels (p = 5.00×10(-7 in first stage, p = 1.34×10(-3 in second stage, and p = 4.22×10(-9 when combined. Besides, smoking was identified to be associated with IgM levels in both stages (P0.05. It is suggested that TNFSF13 may be a susceptibility gene affecting serum IgM levels in Chinese male population.

  5. Using regulatory and epistatic networks to extend the findings of a genome scan: identifying the gene drivers of pigmentation in merino sheep.

    Science.gov (United States)

    García-Gámez, Elsa; Reverter, Antonio; Whan, Vicki; McWilliam, Sean M; Arranz, Juan José; Kijas, James

    2011-01-01

    Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino sheep, by analysing multiple data types using a systems approach. First, a case control analysis of 49,034 ovine SNP was performed which confirmed a multigenic basis for the condition. We combined these results with gene expression data from five tissue types analysed with a skin-specific microarray. Promoter sequence analysis of differentially expressed genes allowed us to reverse-engineer a regulatory network. Likewise, by testing two-loci models derived from all pair-wise comparisons across piebald-associated SNP, we generated an epistatic network. At the intersection of both networks, we identified thirteen genes with insulin-like growth factor binding protein 7 (IGFBP7), platelet-derived growth factor alpha (PDGFRA) and the tetraspanin platelet activator CD9 at the kernel of the intersection. Further, we report a number of differentially expressed genes in regions containing highly associated SNP including ATRN, DOCK7, FGFR1OP, GLI3, SILV and TBX15. The application of network theory facilitated co-analysis of genetic variation with gene expression, recapitulated aspects of the known molecular biology of skin pigmentation and provided insights into the transcription regulation and epistatic interactions involved in piebald Merino sheep.

  6. Using regulatory and epistatic networks to extend the findings of a genome scan: identifying the gene drivers of pigmentation in merino sheep.

    Directory of Open Access Journals (Sweden)

    Elsa García-Gámez

    Full Text Available Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino sheep, by analysing multiple data types using a systems approach. First, a case control analysis of 49,034 ovine SNP was performed which confirmed a multigenic basis for the condition. We combined these results with gene expression data from five tissue types analysed with a skin-specific microarray. Promoter sequence analysis of differentially expressed genes allowed us to reverse-engineer a regulatory network. Likewise, by testing two-loci models derived from all pair-wise comparisons across piebald-associated SNP, we generated an epistatic network. At the intersection of both networks, we identified thirteen genes with insulin-like growth factor binding protein 7 (IGFBP7, platelet-derived growth factor alpha (PDGFRA and the tetraspanin platelet activator CD9 at the kernel of the intersection. Further, we report a number of differentially expressed genes in regions containing highly associated SNP including ATRN, DOCK7, FGFR1OP, GLI3, SILV and TBX15. The application of network theory facilitated co-analysis of genetic variation with gene expression, recapitulated aspects of the known molecular biology of skin pigmentation and provided insights into the transcription regulation and epistatic interactions involved in piebald Merino sheep.

  7. A genome scan for quantitative trait loci affecting grain yield and its components of maize both in single-and two-locus levels

    Institute of Scientific and Technical Information of China (English)

    YAN Jianbing; TANG Hua; HUANG Yiqin; ZHENG Yonglian; SUBHASH Chander; LI Jiansheng

    2006-01-01

    By adding thirty-one markers in the previous linkage map, a new genetic linkage map containing 205 markers was constructed, spanning a total of 2305.4 cM with an average interval of 11.2 cM. The genotypic errors in the whole genome were detected by the statistical method and removed manually. The precision of the linkage map was improved significantly. Main and epistatic QTL were detected by R/qtl, and main QTL were confirmed and refined by multiple interval mapping (MIM). Finally, MIM detected seven QTL for rows number, and five QTL for each grain yield, kernels per row and 100-kernel weight. The contribution to genetic variations of QTL varied from 35.3% for grain yield to 61.5% for rows number. Only kernels per row exhibited significant epistatic interactions between QTL. Twenty-four epistatic QTL were detected which distributed on almost all the ten chromosomes. About two-third epistatic QTL were observed between main QTL and another locus, which had no significant effects. These results indicate rather clearly that there are a number of QTL affecting trait expressions, not directly but indirectly through interactions with other loci. Thus, epistatic QTL effects may play a crucial role, if not more important than main QTL effects, in the genetic variation for the measured traits in present study.

  8. Current trends in Bayesian methodology with applications

    CERN Document Server

    Upadhyay, Satyanshu K; Dey, Dipak K; Loganathan, Appaia

    2015-01-01

    Collecting Bayesian material scattered throughout the literature, Current Trends in Bayesian Methodology with Applications examines the latest methodological and applied aspects of Bayesian statistics. The book covers biostatistics, econometrics, reliability and risk analysis, spatial statistics, image analysis, shape analysis, Bayesian computation, clustering, uncertainty assessment, high-energy astrophysics, neural networking, fuzzy information, objective Bayesian methodologies, empirical Bayes methods, small area estimation, and many more topics.Each chapter is self-contained and focuses on

  9. Bayesian Analysis of High Dimensional Classification

    Science.gov (United States)

    Mukhopadhyay, Subhadeep; Liang, Faming

    2009-12-01

    Modern data mining and bioinformatics have presented an important playground for statistical learning techniques, where the number of input variables is possibly much larger than the sample size of the training data. In supervised learning, logistic regression or probit regression can be used to model a binary output and form perceptron classification rules based on Bayesian inference. In these cases , there is a lot of interest in searching for sparse model in High Dimensional regression(/classification) setup. we first discuss two common challenges for analyzing high dimensional data. The first one is the curse of dimensionality. The complexity of many existing algorithms scale exponentially with the dimensionality of the space and by virtue of that algorithms soon become computationally intractable and therefore inapplicable in many real applications. secondly, multicollinearities among the predictors which severely slowdown the algorithm. In order to make Bayesian analysis operational in high dimension we propose a novel 'Hierarchical stochastic approximation monte carlo algorithm' (HSAMC), which overcomes the curse of dimensionality, multicollinearity of predictors in high dimension and also it possesses the self-adjusting mechanism to avoid the local minima separated by high energy barriers. Models and methods are illustrated by simulation inspired from from the feild of genomics. Numerical results indicate that HSAMC can work as a general model selection sampler in high dimensional complex model space.

  10. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  11. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming

    2013-07-26

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  12. Irregular-Time Bayesian Networks

    CERN Document Server

    Ramati, Michael

    2012-01-01

    In many fields observations are performed irregularly along time, due to either measurement limitations or lack of a constant immanent rate. While discrete-time Markov models (as Dynamic Bayesian Networks) introduce either inefficient computation or an information loss to reasoning about such processes, continuous-time Markov models assume either a discrete state space (as Continuous-Time Bayesian Networks), or a flat continuous state space (as stochastic dif- ferential equations). To address these problems, we present a new modeling class called Irregular-Time Bayesian Networks (ITBNs), generalizing Dynamic Bayesian Networks, allowing substantially more compact representations, and increasing the expressivity of the temporal dynamics. In addition, a globally optimal solution is guaranteed when learning temporal systems, provided that they are fully observed at the same irregularly spaced time-points, and a semiparametric subclass of ITBNs is introduced to allow further adaptation to the irregular nature of t...

  13. Bayesian Tracking of Visual Objects

    Science.gov (United States)

    Zheng, Nanning; Xue, Jianru

    Tracking objects in image sequences involves performing motion analysis at the object level, which is becoming an increasingly important technology in a wide range of computer video applications, including video teleconferencing, security and surveillance, video segmentation, and editing. In this chapter, we focus on sequential Bayesian estimation techniques for visual tracking. We first introduce the sequential Bayesian estimation framework, which acts as the theoretic basis for visual tracking. Then, we present approaches to constructing representation models for specific objects.

  14. Bayesian Networks and Influence Diagrams

    DEFF Research Database (Denmark)

    Kjærulff, Uffe Bro; Madsen, Anders Læsø

     Probabilistic networks, also known as Bayesian networks and influence diagrams, have become one of the most promising technologies in the area of applied artificial intelligence, offering intuitive, efficient, and reliable methods for diagnosis, prediction, decision making, classification......, troubleshooting, and data mining under uncertainty. Bayesian Networks and Influence Diagrams: A Guide to Construction and Analysis provides a comprehensive guide for practitioners who wish to understand, construct, and analyze intelligent systems for decision support based on probabilistic networks. Intended...

  15. Bayesian Inference: with ecological applications

    Science.gov (United States)

    Link, William A.; Barker, Richard J.

    2010-01-01

    This text provides a mathematically rigorous yet accessible and engaging introduction to Bayesian inference with relevant examples that will be of interest to biologists working in the fields of ecology, wildlife management and environmental studies as well as students in advanced undergraduate statistics.. This text opens the door to Bayesian inference, taking advantage of modern computational efficiencies and easily accessible software to evaluate complex hierarchical models.

  16. A Focused Bayesian Information Criterion

    OpenAIRE

    Georges Nguefack-Tsague; Ingo Bulla

    2014-01-01

    Myriads of model selection criteria (Bayesian and frequentist) have been proposed in the literature aiming at selecting a single model regardless of its intended use. An honorable exception in the frequentist perspective is the “focused information criterion” (FIC) aiming at selecting a model based on the parameter of interest (focus). This paper takes the same view in the Bayesian context; that is, a model may be good for one estimand but bad for another. The proposed method exploits the Bay...

  17. Bayesian analysis of CCDM Models

    OpenAIRE

    Jesus, J. F.; Valentim, R.; Andrade-Oliveira, F.

    2016-01-01

    Creation of Cold Dark Matter (CCDM), in the context of Einstein Field Equations, leads to negative creation pressure, which can be used to explain the accelerated expansion of the Universe. In this work we tested six different spatially flat models for matter creation using statistical tools, at light of SN Ia data: Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and Bayesian Evidence (BE). These approaches allow to compare models considering goodness of fit and numbe...

  18. Bayesian Methods for Statistical Analysis

    OpenAIRE

    Puza, Borek

    2015-01-01

    Bayesian methods for statistical analysis is a book on statistical methods for analysing a wide variety of data. The book consists of 12 chapters, starting with basic concepts and covering numerous topics, including Bayesian estimation, decision theory, prediction, hypothesis testing, hierarchical models, Markov chain Monte Carlo methods, finite population inference, biased sampling and nonignorable nonresponse. The book contains many exercises, all with worked solutions, including complete c...

  19. Disentangling Pleiotropy along the Genome using Sparse Latent Variable Models

    DEFF Research Database (Denmark)

    Janss, Luc

    Bayesian models are described that use atent variables to model covariances. These models are flexible, scale up linearly in the number of traits, and allow separating covariance structures in different components at the trait level and at the genomic level. Multi-trait version of the BayesA (MT......-BA) and Bayesian LASSO (MT-BL) are described that model heterogeneous variance and covariance over the genome, and a model that directly models multiple genomic breeding values (MT-MG), representing different genomic covariance structures. The models are demonstrated on a mouse data set to model the genomic...

  20. Head CT scan

    Science.gov (United States)

    Brain CT; Cranial CT; CT scan - skull; CT scan - head; CT scan - orbits; CT scan - sinuses; Computed tomography - cranial; CAT scan - brain ... hold your breath for short periods. A complete scan usually take only 30 seconds to a few ...

  1. Dynamic Batch Bayesian Optimization

    CERN Document Server

    Azimi, Javad; Fern, Xiaoli

    2011-01-01

    Bayesian optimization (BO) algorithms try to optimize an unknown function that is expensive to evaluate using minimum number of evaluations/experiments. Most of the proposed algorithms in BO are sequential, where only one experiment is selected at each iteration. This method can be time inefficient when each experiment takes a long time and more than one experiment can be ran concurrently. On the other hand, requesting a fix-sized batch of experiments at each iteration causes performance inefficiency in BO compared to the sequential policies. In this paper, we present an algorithm that asks a batch of experiments at each time step t where the batch size p_t is dynamically determined in each step. Our algorithm is based on the observation that the sequence of experiments selected by the sequential policy can sometimes be almost independent from each other. Our algorithm identifies such scenarios and request those experiments at the same time without degrading the performance. We evaluate our proposed method us...

  2. Bayesian estimation of the discrete coefficient of determination.

    Science.gov (United States)

    Chen, Ting; Braga-Neto, Ulisses M

    2016-12-01

    The discrete coefficient of determination (CoD) measures the nonlinear interaction between discrete predictor and target variables and has had far-reaching applications in Genomic Signal Processing. Previous work has addressed the inference of the discrete CoD using classical parametric and nonparametric approaches. In this paper, we introduce a Bayesian framework for the inference of the discrete CoD. We derive analytically the optimal minimum mean-square error (MMSE) CoD estimator, as well as a CoD estimator based on the Optimal Bayesian Predictor (OBP). For the latter estimator, exact expressions for its bias, variance, and root-mean-square (RMS) are given. The accuracy of both Bayesian CoD estimators with non-informative and informative priors, under fixed or random parameters, is studied via analytical and numerical approaches. We also demonstrate the application of the proposed Bayesian approach in the inference of gene regulatory networks, using gene-expression data from a previously published study on metastatic melanoma.

  3. Deviance Information Criterion (DIC) in Bayesian Multiple QTL Mapping.

    Science.gov (United States)

    Shriner, Daniel; Yi, Nengjun

    2009-03-15

    Mapping multiple quantitative trait loci (QTL) is commonly viewed as a problem of model selection. Various model selection criteria have been proposed, primarily in the non-Bayesian framework. The deviance information criterion (DIC) is the most popular criterion for Bayesian model selection and model comparison but has not been applied to Bayesian multiple QTL mapping. A derivation of the DIC is presented for multiple interacting QTL models and calculation of the DIC is demonstrated using posterior samples generated by Markov chain Monte Carlo (MCMC) algorithms. The DIC measures posterior predictive error by penalizing the fit of a model (deviance) by its complexity, determined by the effective number of parameters. The effective number of parameters simultaneously accounts for the sample size, the cross design, the number and lengths of chromosomes, covariates, the number of QTL, the type of QTL effects, and QTL effect sizes. The DIC provides a computationally efficient way to perform sensitivity analysis and can be used to quantitatively evaluate if including environmental effects, gene-gene interactions, and/or gene-environment interactions in the prior specification is worth the extra parameterization. The DIC has been implemented in the freely available package R/qtlbim, which greatly facilitates the general usage of Bayesian methodology for genome-wide interacting QTL analysis.

  4. A Bayesian Approach for Graph-constrained Estimation for High-dimensional Regression.

    Science.gov (United States)

    Sun, Hokeun; Li, Hongzhe

    Many different biological processes are represented by network graphs such as regulatory networks, metabolic pathways, and protein-protein interaction networks. Since genes that are linked on the networks usually have biologically similar functions, the linked genes form molecular modules to affect the clinical phenotypes/outcomes. Similarly, in large-scale genetic association studies, many SNPs are in high linkage disequilibrium (LD), which can also be summarized as a LD graph. In order to incorporate the graph information into regression analysis with high dimensional genomic data as predictors, we introduce a Bayesian approach for graph-constrained estimation (Bayesian GRACE) and regularization, which controls the amount of regularization for sparsity and smoothness of the regression coefficients. The Bayesian estimation with their posterior distributions can provide credible intervals for the estimates of the regression coefficients along with standard errors. The deviance information criterion (DIC) is applied for model assessment and tuning parameter selection. The performance of the proposed Bayesian approach is evaluated through simulation studies and is compared with Bayesian Lasso and Bayesian Elastic-net procedures. We demonstrate our method in an analysis of data from a case-control genome-wide association study of neuroblastoma using a weighted LD graph.

  5. Bayesian Model Selection and Statistical Modeling

    CERN Document Server

    Ando, Tomohiro

    2010-01-01

    Bayesian model selection is a fundamental part of the Bayesian statistical modeling process. The quality of these solutions usually depends on the goodness of the constructed Bayesian model. Realizing how crucial this issue is, many researchers and practitioners have been extensively investigating the Bayesian model selection problem. This book provides comprehensive explanations of the concepts and derivations of the Bayesian approach for model selection and related criteria, including the Bayes factor, the Bayesian information criterion (BIC), the generalized BIC, and the pseudo marginal lik

  6. Bayesian seismic AVO inversion

    Energy Technology Data Exchange (ETDEWEB)

    Buland, Arild

    2002-07-01

    A new linearized AVO inversion technique is developed in a Bayesian framework. The objective is to obtain posterior distributions for P-wave velocity, S-wave velocity and density. Distributions for other elastic parameters can also be assessed, for example acoustic impedance, shear impedance and P-wave to S-wave velocity ratio. The inversion algorithm is based on the convolutional model and a linearized weak contrast approximation of the Zoeppritz equation. The solution is represented by a Gaussian posterior distribution with explicit expressions for the posterior expectation and covariance, hence exact prediction intervals for the inverted parameters can be computed under the specified model. The explicit analytical form of the posterior distribution provides a computationally fast inversion method. Tests on synthetic data show that all inverted parameters were almost perfectly retrieved when the noise approached zero. With realistic noise levels, acoustic impedance was the best determined parameter, while the inversion provided practically no information about the density. The inversion algorithm has also been tested on a real 3-D dataset from the Sleipner Field. The results show good agreement with well logs but the uncertainty is high. The stochastic model includes uncertainties of both the elastic parameters, the wavelet and the seismic and well log data. The posterior distribution is explored by Markov chain Monte Carlo simulation using the Gibbs sampler algorithm. The inversion algorithm has been tested on a seismic line from the Heidrun Field with two wells located on the line. The uncertainty of the estimated wavelet is low. In the Heidrun examples the effect of including uncertainty of the wavelet and the noise level was marginal with respect to the AVO inversion results. We have developed a 3-D linearized AVO inversion method with spatially coupled model parameters where the objective is to obtain posterior distributions for P-wave velocity, S

  7. Bayesian microsaccade detection

    Science.gov (United States)

    Mihali, Andra; van Opheusden, Bas; Ma, Wei Ji

    2017-01-01

    Microsaccades are high-velocity fixational eye movements, with special roles in perception and cognition. The default microsaccade detection method is to determine when the smoothed eye velocity exceeds a threshold. We have developed a new method, Bayesian microsaccade detection (BMD), which performs inference based on a simple statistical model of eye positions. In this model, a hidden state variable changes between drift and microsaccade states at random times. The eye position is a biased random walk with different velocity distributions for each state. BMD generates samples from the posterior probability distribution over the eye state time series given the eye position time series. Applied to simulated data, BMD recovers the “true” microsaccades with fewer errors than alternative algorithms, especially at high noise. Applied to EyeLink eye tracker data, BMD detects almost all the microsaccades detected by the default method, but also apparent microsaccades embedded in high noise—although these can also be interpreted as false positives. Next we apply the algorithms to data collected with a Dual Purkinje Image eye tracker, whose higher precision justifies defining the inferred microsaccades as ground truth. When we add artificial measurement noise, the inferences of all algorithms degrade; however, at noise levels comparable to EyeLink data, BMD recovers the “true” microsaccades with 54% fewer errors than the default algorithm. Though unsuitable for online detection, BMD has other advantages: It returns probabilities rather than binary judgments, and it can be straightforwardly adapted as the generative model is refined. We make our algorithm available as a software package. PMID:28114483

  8. Maximum margin Bayesian network classifiers.

    Science.gov (United States)

    Pernkopf, Franz; Wohlmayr, Michael; Tschiatschek, Sebastian

    2012-03-01

    We present a maximum margin parameter learning algorithm for Bayesian network classifiers using a conjugate gradient (CG) method for optimization. In contrast to previous approaches, we maintain the normalization constraints on the parameters of the Bayesian network during optimization, i.e., the probabilistic interpretation of the model is not lost. This enables us to handle missing features in discriminatively optimized Bayesian networks. In experiments, we compare the classification performance of maximum margin parameter learning to conditional likelihood and maximum likelihood learning approaches. Discriminative parameter learning significantly outperforms generative maximum likelihood estimation for naive Bayes and tree augmented naive Bayes structures on all considered data sets. Furthermore, maximizing the margin dominates the conditional likelihood approach in terms of classification performance in most cases. We provide results for a recently proposed maximum margin optimization approach based on convex relaxation. While the classification results are highly similar, our CG-based optimization is computationally up to orders of magnitude faster. Margin-optimized Bayesian network classifiers achieve classification performance comparable to support vector machines (SVMs) using fewer parameters. Moreover, we show that unanticipated missing feature values during classification can be easily processed by discriminatively optimized Bayesian network classifiers, a case where discriminative classifiers usually require mechanisms to complete unknown feature values in the data first.

  9. A Focused Bayesian Information Criterion

    Directory of Open Access Journals (Sweden)

    Georges Nguefack-Tsague

    2014-01-01

    Full Text Available Myriads of model selection criteria (Bayesian and frequentist have been proposed in the literature aiming at selecting a single model regardless of its intended use. An honorable exception in the frequentist perspective is the “focused information criterion” (FIC aiming at selecting a model based on the parameter of interest (focus. This paper takes the same view in the Bayesian context; that is, a model may be good for one estimand but bad for another. The proposed method exploits the Bayesian model averaging (BMA machinery to obtain a new criterion, the focused Bayesian model averaging (FoBMA, for which the best model is the one whose estimate is closest to the BMA estimate. In particular, for two models, this criterion reduces to the classical Bayesian model selection scheme of choosing the model with the highest posterior probability. The new method is applied in linear regression, logistic regression, and survival analysis. This criterion is specially important in epidemiological studies in which the objective is often to determine a risk factor (focus for a disease, adjusting for potential confounding factors.

  10. Bayesian and L$_\\mathbf{1}$ Approaches to Sparse Unsupervised Learning

    CERN Document Server

    Mohamed, Shakir; Ghahramani, Zoubin

    2011-01-01

    The use of $L_1$ regularisation for sparse learning has generated immense research interest, with successful application in such diverse areas as signal acquisition, image coding, genomics and collaborative filtering. While existing work highlights the many advantages of $L_1$ methods, in this paper we find that $L_1$ regularisation often dramatically underperforms in terms of predictive performance when compared with other methods for inferring sparsity. We focus on unsupervised latent variable models, and develop $L_1$ minimising factor models, Bayesian variants of "$L_1$", and Bayesian models with a stronger $L_0$-like sparsity induced through spike-and-slab distributions. These spike-and-slab Bayesian factor models encourage sparsity while accounting for uncertainty in a principled manner and avoiding unnecessary shrinkage of non-zero values. We demonstrate on a number of data sets that in practice spike-and-slab Bayesian methods outperform $L_1$ minimisation, even on a computational budget. We thus highl...

  11. Patterns of positive selection in six Mammalian genomes.

    Directory of Open Access Journals (Sweden)

    Carolin Kosiol

    Full Text Available Genome-wide scans for positively selected genes (PSGs in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of approximately 16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05, according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible "selection histories" of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for

  12. Bayesian Methods and Universal Darwinism

    CERN Document Server

    Campbell, John

    2010-01-01

    Bayesian methods since the time of Laplace have been understood by their practitioners as closely aligned to the scientific method. Indeed a recent champion of Bayesian methods, E. T. Jaynes, titled his textbook on the subject Probability Theory: the Logic of Science. Many philosophers of science including Karl Popper and Donald Campbell have interpreted the evolution of Science as a Darwinian process consisting of a 'copy with selective retention' algorithm abstracted from Darwin's theory of Natural Selection. Arguments are presented for an isomorphism between Bayesian Methods and Darwinian processes. Universal Darwinism, as the term has been developed by Richard Dawkins, Daniel Dennett and Susan Blackmore, is the collection of scientific theories which explain the creation and evolution of their subject matter as due to the operation of Darwinian processes. These subject matters span the fields of atomic physics, chemistry, biology and the social sciences. The principle of Maximum Entropy states that system...

  13. Probability biases as Bayesian inference

    Directory of Open Access Journals (Sweden)

    Andre; C. R. Martins

    2006-11-01

    Full Text Available In this article, I will show how several observed biases in human probabilistic reasoning can be partially explained as good heuristics for making inferences in an environment where probabilities have uncertainties associated to them. Previous results show that the weight functions and the observed violations of coalescing and stochastic dominance can be understood from a Bayesian point of view. We will review those results and see that Bayesian methods should also be used as part of the explanation behind other known biases. That means that, although the observed errors are still errors under the be understood as adaptations to the solution of real life problems. Heuristics that allow fast evaluations and mimic a Bayesian inference would be an evolutionary advantage, since they would give us an efficient way of making decisions. %XX In that sense, it should be no surprise that humans reason with % probability as it has been observed.

  14. Introduction to Bayesian modelling in dental research.

    Science.gov (United States)

    Gilthorpe, M S; Maddick, I H; Petrie, A

    2000-12-01

    To explain the concepts and application of Bayesian modelling and how it can be applied to the analysis of dental research data. Methodological in nature, this article introduces Bayesian modelling through hypothetical dental examples. The synthesis of RCT results with previous evidence, including expert opinion, is used to illustrate full Bayesian modelling. Meta-analysis, in the form of empirical Bayesian modelling, is introduced. An example of full Bayesian modelling is described for the synthesis of evidence from several studies that investigate the success of root canal treatment. Hierarchical (Bayesian) modelling is demonstrated for a survey of childhood caries, where surface data is nested within subjects. Bayesian methods enhance interpretation of research evidence through the synthesis of information from multiple sources. Bayesian modelling is now readily accessible to clinical researchers and is able to augment the application of clinical decision making in the development of guidelines and clinical practice.

  15. Bayesian modeling using WinBUGS

    CERN Document Server

    Ntzoufras, Ioannis

    2009-01-01

    A hands-on introduction to the principles of Bayesian modeling using WinBUGS Bayesian Modeling Using WinBUGS provides an easily accessible introduction to the use of WinBUGS programming techniques in a variety of Bayesian modeling settings. The author provides an accessible treatment of the topic, offering readers a smooth introduction to the principles of Bayesian modeling with detailed guidance on the practical implementation of key principles. The book begins with a basic introduction to Bayesian inference and the WinBUGS software and goes on to cover key topics, including: Markov Chain Monte Carlo algorithms in Bayesian inference Generalized linear models Bayesian hierarchical models Predictive distribution and model checking Bayesian model and variable evaluation Computational notes and screen captures illustrate the use of both WinBUGS as well as R software to apply the discussed techniques. Exercises at the end of each chapter allow readers to test their understanding of the presented concepts and all ...

  16. Bayesian Concordance Correlation Coefficient with Application to Repeatedly Measured Data

    Directory of Open Access Journals (Sweden)

    Atanu BHATTACHARJEE

    2015-10-01

    Full Text Available Objective: In medical research, Lin's classical concordance correlation coefficient (CCC is frequently applied to evaluate the similarity of the measurements produced by different raters or methods on the same subjects. It is particularly useful for continuous data. The objective of this paper is to propose the Bayesian counterpart to compute CCC for continuous data. Material and Methods: A total of 33 patients of astrocytoma brain treated in the Department of Radiation Oncology at Malabar Cancer Centre is enrolled in this work. It is a continuous data of tumor volume and tumor size repeatedly measured during baseline pretreatment workup and post surgery follow-ups for all patients. The tumor volume and tumor size are measured separately by MRI and CT scan. The agreement of measurement between MRI and CT scan is calculated through CCC. The statistical inference is performed through Markov Chain Monte Carlo (MCMC technique. Results: Bayesian CCC is found suitable to get prominent evidence for test statistics to explore the relation between concordance measurements. The posterior mean estimates and 95% credible interval of CCC on tumor size and tumor volume are observed with 0.96(0.87,0.99 and 0.98(0.95,0.99 respectively. Conclusion: The Bayesian inference is adopted for development of the computational algorithm. The approach illustrated in this work provides the researchers an opportunity to find out the most appropriate model for specific data and apply CCC to fulfill the desired hypothesis.

  17. Improved inference in Bayesian segmentation using Monte Carlo sampling: Application to hippocampal subfield volumetry

    DEFF Research Database (Denmark)

    Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Van Leemput, Koen

    2013-01-01

    Many segmentation algorithms in medical image analysis use Bayesian modeling to augment local image appearance with prior anatomical knowledge. Such methods often contain a large number of free parameters that are first estimated and then kept fixed during the actual segmentation process. However......, a faithful Bayesian analysis would marginalize over such parameters, accounting for their uncertainty by considering all possible values they may take. Here we propose to incorporate this uncertainty into Bayesian segmentation methods in order to improve the inference process. In particular, we approximate...... the required marginalization over model parameters using computationally efficient Markov chain Monte Carlo techniques. We illustrate the proposed approach using a recently developed Bayesian method for the segmentation of hippocampal subfields in brain MRI scans, showing a significant improvement...

  18. Improved inference in Bayesian segmentation using Monte Carlo sampling: application to hippocampal subfield volumetry.

    Science.gov (United States)

    Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Van Leemput, Koen

    2013-10-01

    Many segmentation algorithms in medical image analysis use Bayesian modeling to augment local image appearance with prior anatomical knowledge. Such methods often contain a large number of free parameters that are first estimated and then kept fixed during the actual segmentation process. However, a faithful Bayesian analysis would marginalize over such parameters, accounting for their uncertainty by considering all possible values they may take. Here we propose to incorporate this uncertainty into Bayesian segmentation methods in order to improve the inference process. In particular, we approximate the required marginalization over model parameters using computationally efficient Markov chain Monte Carlo techniques. We illustrate the proposed approach using a recently developed Bayesian method for the segmentation of hippocampal subfields in brain MRI scans, showing a significant improvement in an Alzheimer's disease classification task. As an additional benefit, the technique also allows one to compute informative "error bars" on the volume estimates of individual structures.

  19. Bayesian Missile System Reliability from Point Estimates

    Science.gov (United States)

    2014-10-28

    OCT 2014 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Bayesian Missile System Reliability from Point Estimates 5a. CONTRACT...Principle (MEP) to convert point estimates to probability distributions to be used as priors for Bayesian reliability analysis of missile data, and...illustrate this approach by applying the priors to a Bayesian reliability model of a missile system. 15. SUBJECT TERMS priors, Bayesian , missile

  20. Thyroid Scan and Uptake

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  1. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  2. Thyroid Scan and Uptake

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses small ... Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a type ...

  3. 3D Bayesian contextual classifiers

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    2000-01-01

    We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours.......We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours....

  4. Attention in a bayesian framework

    DEFF Research Database (Denmark)

    Whiteley, Louise Emma; Sahani, Maneesh

    2012-01-01

    , and include both selective phenomena, where attention is invoked by cues that point to particular stimuli, and integrative phenomena, where attention is invoked dynamically by endogenous processing. However, most previous Bayesian accounts of attention have focused on describing relatively simple experimental......The behavioral phenomena of sensory attention are thought to reflect the allocation of a limited processing resource, but there is little consensus on the nature of the resource or why it should be limited. Here we argue that a fundamental bottleneck emerges naturally within Bayesian models...

  5. Bayesian test and Kuhn's paradigm

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoping

    2006-01-01

    Kuhn's theory of paradigm reveals a pattern of scientific progress,in which normal science alternates with scientific revolution.But Kuhn underrated too much the function of scientific test in his pattern,because he focuses all his attention on the hypothetico-deductive schema instead of Bayesian schema.This paper employs Bayesian schema to re-examine Kuhn's theory of paradigm,to uncover its logical and rational components,and to illustrate the tensional structure of logic and belief,rationality and irrationality,in the process of scientific revolution.

  6. Perception, illusions and Bayesian inference.

    Science.gov (United States)

    Nour, Matthew M; Nour, Joseph M

    2015-01-01

    Descriptive psychopathology makes a distinction between veridical perception and illusory perception. In both cases a perception is tied to a sensory stimulus, but in illusions the perception is of a false object. This article re-examines this distinction in light of new work in theoretical and computational neurobiology, which views all perception as a form of Bayesian statistical inference that combines sensory signals with prior expectations. Bayesian perceptual inference can solve the 'inverse optics' problem of veridical perception and provides a biologically plausible account of a number of illusory phenomena, suggesting that veridical and illusory perceptions are generated by precisely the same inferential mechanisms.

  7. Bayesian networks: a powerful tool for systems biology study

    Institute of Scientific and Technical Information of China (English)

    Xiu-Jie WANG

    2010-01-01

    @@ Higher Education Press and Springer-Verlag Berlin Heidelberg 2010The wide application of omics research approaches caused a burst of biological data in the past decade, and also promoted the growth of systems biology, a research field that studies biological questions from a genome-wide point of view. One feature of systems biology study is to integrate and identify. Not only experiments are carried out at whole-genome scales, but also data from various resources, such as genomics, transcriptomics, proteomics,and metabolics data, need to be integrated to identify correlations among targeted entities. Therefore, plenty amounts of experimental data, robust statistical methods, and reliable network construction models are indispensable for systems biology study. Among the available network construction models, Bayesian network is considered as one of the most effective methods available so far for biological network predictions (Pe'er, 2005).

  8. Plug & Play object oriented Bayesian networks

    DEFF Research Database (Denmark)

    Bangsø, Olav; Flores, J.; Jensen, Finn Verner

    2003-01-01

    Object oriented Bayesian networks have proven themselves useful in recent years. The idea of applying an object oriented approach to Bayesian networks has extended their scope to larger domains that can be divided into autonomous but interrelated entities. Object oriented Bayesian networks have b...

  9. A Bayesian Nonparametric Approach to Test Equating

    Science.gov (United States)

    Karabatsos, George; Walker, Stephen G.

    2009-01-01

    A Bayesian nonparametric model is introduced for score equating. It is applicable to all major equating designs, and has advantages over previous equating models. Unlike the previous models, the Bayesian model accounts for positive dependence between distributions of scores from two tests. The Bayesian model and the previous equating models are…

  10. Bayesian Model Averaging for Propensity Score Analysis

    Science.gov (United States)

    Kaplan, David; Chen, Jianshen

    2013-01-01

    The purpose of this study is to explore Bayesian model averaging in the propensity score context. Previous research on Bayesian propensity score analysis does not take into account model uncertainty. In this regard, an internally consistent Bayesian framework for model building and estimation must also account for model uncertainty. The…

  11. Bayesian networks and food security - An introduction

    NARCIS (Netherlands)

    Stein, A.

    2004-01-01

    This paper gives an introduction to Bayesian networks. Networks are defined and put into a Bayesian context. Directed acyclical graphs play a crucial role here. Two simple examples from food security are addressed. Possible uses of Bayesian networks for implementation and further use in decision sup

  12. A Bayesian Framework for SNP Identification

    Energy Technology Data Exchange (ETDEWEB)

    Webb-Robertson, Bobbie-Jo M.; Havre, Susan L.; Payne, Deborah A.

    2005-07-01

    Current proteomics techniques, such as mass spectrometry, focus on protein identification, usually ignoring most types of modifications beyond post-translational modifications, with the assumption that only a small number of peptides have to be matched to a protein for a positive identification. However, not all proteins are being identified with current techniques and improved methods to locate points of mutation are becoming a necessity. In the case when single-nucleotide polymorphisms (SNPs) are observed, brute force is the most common method to locate them, quickly becoming computationally unattractive as the size of the database associated with the model organism grows. We have developed a Bayesian model for SNPs, BSNP, incorporating evolutionary information at both the nucleotide and amino acid levels. Formulating SNPs as a Bayesian inference problem allows probabilities of interest to be easily obtained, for example the probability of a specific SNP or specific type of mutation over a gene or entire genome. Three SNP databases were observed in the evaluation of the BSNP model; the first SNP database is a disease specific gene in human, hemoglobin, the second is also a disease specific gene in human, p53, and the third is a more general SNP database for multiple genes in mouse. We validate that the BSNP model assigns higher posterior probabilities to the SNPs defined in all three separate databases than can be attributed to chance under specific evolutionary information, for example the amino acid model described by Majewski and Ott in conjunction with either the four-parameter nucleotide model by Bulmer or seven-parameter nucleotide model by Majewski and Ott.

  13. Bayesian Classification of Image Structures

    DEFF Research Database (Denmark)

    Goswami, Dibyendu; Kalkan, Sinan; Krüger, Norbert

    2009-01-01

    In this paper, we describe work on Bayesian classi ers for distinguishing between homogeneous structures, textures, edges and junctions. We build semi-local classiers from hand-labeled images to distinguish between these four different kinds of structures based on the concept of intrinsic dimensi...

  14. Bayesian Analysis of Experimental Data

    Directory of Open Access Journals (Sweden)

    Lalmohan Bhar

    2013-10-01

    Full Text Available Analysis of experimental data from Bayesian point of view has been considered. Appropriate methodology has been developed for application into designed experiments. Normal-Gamma distribution has been considered for prior distribution. Developed methodology has been applied to real experimental data taken from long term fertilizer experiments.

  15. Bayesian Networks and Influence Diagrams

    DEFF Research Database (Denmark)

    Kjærulff, Uffe Bro; Madsen, Anders Læsø

    Bayesian Networks and Influence Diagrams: A Guide to Construction and Analysis, Second Edition, provides a comprehensive guide for practitioners who wish to understand, construct, and analyze intelligent systems for decision support based on probabilistic networks. This new edition contains six new...

  16. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis

    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for salt and pepper noise. The inference in the model is discussed...

  17. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis Linda

    2006-01-01

    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for the salt and pepper noise. The inference in the model is discussed...

  18. Differentiated Bayesian Conjoint Choice Designs

    NARCIS (Netherlands)

    Z. Sándor (Zsolt); M. Wedel (Michel)

    2003-01-01

    textabstractPrevious conjoint choice design construction procedures have produced a single design that is administered to all subjects. This paper proposes to construct a limited set of different designs. The designs are constructed in a Bayesian fashion, taking into account prior uncertainty about

  19. 3-D contextual Bayesian classifiers

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    In this paper we will consider extensions of a series of Bayesian 2-D contextual classification pocedures proposed by Owen (1984) Hjort & Mohn (1984) and Welch & Salter (1971) and Haslett (1985) to 3 spatial dimensions. It is evident that compared to classical pixelwise classification further...

  20. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...

  1. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    2013-01-01

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...

  2. Bayesian Evidence and Model Selection

    CERN Document Server

    Knuth, Kevin H; Malakar, Nabin K; Mubeen, Asim M; Placek, Ben

    2014-01-01

    In this paper we review the concept of the Bayesian evidence and its application to model selection. The theory is presented along with a discussion of analytic, approximate and numerical techniques. Application to several practical examples within the context of signal processing are discussed.

  3. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...

  4. Bayesian stable isotope mixing models

    Science.gov (United States)

    In this paper we review recent advances in Stable Isotope Mixing Models (SIMMs) and place them into an over-arching Bayesian statistical framework which allows for several useful extensions. SIMMs are used to quantify the proportional contributions of various sources to a mixtur...

  5. Naive Bayesian for Email Filtering

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The paper presents a method of email filter based on Naive Bayesian theory that can effectively filter junk mail and illegal mail. Furthermore, the keys of implementation are discussed in detail. The filtering model is obtained from training set of email. The filtering can be done without the users specification of filtering rules.

  6. ANALYSIS OF BAYESIAN CLASSIFIER ACCURACY

    Directory of Open Access Journals (Sweden)

    Felipe Schneider Costa

    2013-01-01

    Full Text Available The naïve Bayes classifier is considered one of the most effective classification algorithms today, competing with more modern and sophisticated classifiers. Despite being based on unrealistic (naïve assumption that all variables are independent, given the output class, the classifier provides proper results. However, depending on the scenario utilized (network structure, number of samples or training cases, number of variables, the network may not provide appropriate results. This study uses a process variable selection, using the chi-squared test to verify the existence of dependence between variables in the data model in order to identify the reasons which prevent a Bayesian network to provide good performance. A detailed analysis of the data is also proposed, unlike other existing work, as well as adjustments in case of limit values between two adjacent classes. Furthermore, variable weights are used in the calculation of a posteriori probabilities, calculated with mutual information function. Tests were applied in both a naïve Bayesian network and a hierarchical Bayesian network. After testing, a significant reduction in error rate has been observed. The naïve Bayesian network presented a drop in error rates from twenty five percent to five percent, considering the initial results of the classification process. In the hierarchical network, there was not only a drop in fifteen percent error rate, but also the final result came to zero.

  7. Bayesian tests of measurement invariance

    NARCIS (Netherlands)

    Verhagen, A.J.; Fox, J.P.

    2013-01-01

    Random item effects models provide a natural framework for the exploration of violations of measurement invariance without the need for anchor items. Within the random item effects modelling framework, Bayesian tests (Bayes factor, deviance information criterion) are proposed which enable multiple m

  8. Bayesian NL interpretation and learning

    NARCIS (Netherlands)

    Zeevat, H.

    2011-01-01

    Everyday natural language communication is normally successful, even though contemporary computational linguistics has shown that NL is characterised by very high degree of ambiguity and the results of stochastic methods are not good enough to explain the high success rate. Bayesian natural language

  9. Bayesian analysis of binary sequences

    Science.gov (United States)

    Torney, David C.

    2005-03-01

    This manuscript details Bayesian methodology for "learning by example", with binary n-sequences encoding the objects under consideration. Priors prove influential; conformable priors are described. Laplace approximation of Bayes integrals yields posterior likelihoods for all n-sequences. This involves the optimization of a definite function over a convex domain--efficiently effectuated by the sequential application of the quadratic program.

  10. Bayesian Networks and Influence Diagrams

    DEFF Research Database (Denmark)

    Kjærulff, Uffe Bro; Madsen, Anders Læsø

    Bayesian Networks and Influence Diagrams: A Guide to Construction and Analysis, Second Edition, provides a comprehensive guide for practitioners who wish to understand, construct, and analyze intelligent systems for decision support based on probabilistic networks. This new edition contains six new...

  11. Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus.

    Directory of Open Access Journals (Sweden)

    Carolina Medina-Gomez

    2012-07-01

    Full Text Available To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11 observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ± 500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD with rs917727 in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P = 2.6 × 10(-31 and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P = 1.42 × 10(-10 for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P = 1.9 × 10(-16 and rs7801723 (P = 8.9 × 10(-28, also mapping to C7orf58 (r(2 = 0.50 with rs4609139. Wnt16 knockout (KO mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of

  12. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease.

    Directory of Open Access Journals (Sweden)

    Eleonora A M Festen

    Full Text Available Crohn's disease (CD and celiac disease (CelD are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls and CD (3,230 cases, 4,829 controls were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD. These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 10⁻⁹, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls and CD (1,835 cases and 1,669 controls cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071 in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55 x 10⁻¹⁰ and 1.38 x 10⁻¹¹ respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a

  13. Bayesian Alternation During Tactile Augmentation

    Directory of Open Access Journals (Sweden)

    Caspar Mathias Goeke

    2016-10-01

    Full Text Available A large number of studies suggest that the integration of multisensory signals by humans is well described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition, rotation only (native condition, and both augmented and native information (bimodal condition. Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants’ responses with a probit model and calculated the just notable difference (JND. Then we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67 than the Bayesian integration model (χred2= 4.34. Slightly higher accuracy showed a non-Bayesian winner takes all model (χred2= 1.64, which either used only native or only augmented values per subject for prediction. However the performance of the Bayesian alternation model could be substantially improved (χred2= 1.09 utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in

  14. Bayesian analysis of rare events

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Daniel, E-mail: straub@tum.de; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

  15. STATISTICAL BAYESIAN ANALYSIS OF EXPERIMENTAL DATA.

    Directory of Open Access Journals (Sweden)

    AHLAM LABDAOUI

    2012-12-01

    Full Text Available The Bayesian researcher should know the basic ideas underlying Bayesian methodology and the computational tools used in modern Bayesian econometrics.  Some of the most important methods of posterior simulation are Monte Carlo integration, importance sampling, Gibbs sampling and the Metropolis- Hastings algorithm. The Bayesian should also be able to put the theory and computational tools together in the context of substantive empirical problems. We focus primarily on recent developments in Bayesian computation. Then we focus on particular models. Inevitably, we combine theory and computation in the context of particular models. Although we have tried to be reasonably complete in terms of covering the basic ideas of Bayesian theory and the computational tools most commonly used by the Bayesian, there is no way we can cover all the classes of models used in econometrics. We propose to the user of analysis of variance and linear regression model.

  16. Bayesian methods for measures of agreement

    CERN Document Server

    Broemeling, Lyle D

    2009-01-01

    Using WinBUGS to implement Bayesian inferences of estimation and testing hypotheses, Bayesian Methods for Measures of Agreement presents useful methods for the design and analysis of agreement studies. It focuses on agreement among the various players in the diagnostic process.The author employs a Bayesian approach to provide statistical inferences based on various models of intra- and interrater agreement. He presents many examples that illustrate the Bayesian mode of reasoning and explains elements of a Bayesian application, including prior information, experimental information, the likelihood function, posterior distribution, and predictive distribution. The appendices provide the necessary theoretical foundation to understand Bayesian methods as well as introduce the fundamentals of programming and executing the WinBUGS software.Taking a Bayesian approach to inference, this hands-on book explores numerous measures of agreement, including the Kappa coefficient, the G coefficient, and intraclass correlation...

  17. Helix Scan: A Scan Design for Diagnosis

    Institute of Scientific and Technical Information of China (English)

    WANG Fei; HU Yu; LI Xiaowei

    2007-01-01

    Scan design is a widely used design-for-testability technique to improve test quality and efficiency. For the scan-designed circuit, test and diagnosis of the scan chain and the circuit is an important process for silicon debug and yield learning. However, conventional scan designs and diagnosis methods abort the subsequent diagnosis process after diagnosing the scan chain if the scan chain is faulty. In this work, we propose a design-for-diagnosis scan strategy called helix scan and a diagnosis algorithm to address this issue. Unlike previous proposed methods, helix scan has the capability to carry on the diagnosis process without losing information when the scan chain is faulty. What is more, it simplifies scan chain diagnosis and achieves high diagnostic resolution as well as accuracy. Experimental results demonstrate the effectiveness of our design.

  18. Lumbar spine CT scan

    Science.gov (United States)

    CAT scan - lumbar spine; Computed axial tomography scan - lumbar spine; Computed tomography scan - lumbar spine; CT - lower back ... your breath for short periods of time. The scan should take only 10 to 15 minutes.

  19. A Sparse Bayesian Learning Algorithm for Longitudinal Image Data.

    Science.gov (United States)

    Sabuncu, Mert R

    2015-10-01

    Longitudinal imaging studies, where serial (multiple) scans are collected on each individual, are becoming increasingly widespread. The field of machine learning has in general neglected the longitudinal design, since many algorithms are built on the assumption that each datapoint is an independent sample. Thus, the application of general purpose machine learning tools to longitudinal image data can be sub-optimal. Here, we present a novel machine learning algorithm designed to handle longitudinal image datasets. Our approach builds on a sparse Bayesian image-based prediction algorithm. Our empirical results demonstrate that the proposed method can offer a significant boost in prediction performance with longitudinal clinical data.

  20. Bayesian Inference for Radio Observations

    CERN Document Server

    Lochner, Michelle; Zwart, Jonathan T L; Smirnov, Oleg; Bassett, Bruce A; Oozeer, Nadeem; Kunz, Martin

    2015-01-01

    (Abridged) New telescopes like the Square Kilometre Array (SKA) will push into a new sensitivity regime and expose systematics, such as direction-dependent effects, that could previously be ignored. Current methods for handling such systematics rely on alternating best estimates of instrumental calibration and models of the underlying sky, which can lead to inaccurate uncertainty estimates and biased results because such methods ignore any correlations between parameters. These deconvolution algorithms produce a single image that is assumed to be a true representation of the sky, when in fact it is just one realisation of an infinite ensemble of images compatible with the noise in the data. In contrast, here we report a Bayesian formalism that simultaneously infers both systematics and science. Our technique, Bayesian Inference for Radio Observations (BIRO), determines all parameters directly from the raw data, bypassing image-making entirely, by sampling from the joint posterior probability distribution. Thi...

  1. Deep Learning and Bayesian Methods

    Science.gov (United States)

    Prosper, Harrison B.

    2017-03-01

    A revolution is underway in which deep neural networks are routinely used to solve diffcult problems such as face recognition and natural language understanding. Particle physicists have taken notice and have started to deploy these methods, achieving results that suggest a potentially significant shift in how data might be analyzed in the not too distant future. We discuss a few recent developments in the application of deep neural networks and then indulge in speculation about how such methods might be used to automate certain aspects of data analysis in particle physics. Next, the connection to Bayesian methods is discussed and the paper ends with thoughts on a significant practical issue, namely, how, from a Bayesian perspective, one might optimize the construction of deep neural networks.

  2. Bayesian approach to rough set

    CERN Document Server

    Marwala, Tshilidzi

    2007-01-01

    This paper proposes an approach to training rough set models using Bayesian framework trained using Markov Chain Monte Carlo (MCMC) method. The prior probabilities are constructed from the prior knowledge that good rough set models have fewer rules. Markov Chain Monte Carlo sampling is conducted through sampling in the rough set granule space and Metropolis algorithm is used as an acceptance criteria. The proposed method is tested to estimate the risk of HIV given demographic data. The results obtained shows that the proposed approach is able to achieve an average accuracy of 58% with the accuracy varying up to 66%. In addition the Bayesian rough set give the probabilities of the estimated HIV status as well as the linguistic rules describing how the demographic parameters drive the risk of HIV.

  3. BAYESIAN IMAGE RESTORATION, USING CONFIGURATIONS

    Directory of Open Access Journals (Sweden)

    Thordis Linda Thorarinsdottir

    2011-05-01

    Full Text Available In this paper, we develop a Bayesian procedure for removing noise from images that can be viewed as noisy realisations of random sets in the plane. The procedure utilises recent advances in configuration theory for noise free random sets, where the probabilities of observing the different boundary configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for salt and pepper noise. The inference in the model is discussed in detail for 3 X 3 and 5 X 5 configurations and examples of the performance of the procedure are given.

  4. Bayesian Source Separation and Localization

    CERN Document Server

    Knuth, K H

    1998-01-01

    The problem of mixed signals occurs in many different contexts; one of the most familiar being acoustics. The forward problem in acoustics consists of finding the sound pressure levels at various detectors resulting from sound signals emanating from the active acoustic sources. The inverse problem consists of using the sound recorded by the detectors to separate the signals and recover the original source waveforms. In general, the inverse problem is unsolvable without additional information. This general problem is called source separation, and several techniques have been developed that utilize maximum entropy, minimum mutual information, and maximum likelihood. In previous work, it has been demonstrated that these techniques can be recast in a Bayesian framework. This paper demonstrates the power of the Bayesian approach, which provides a natural means for incorporating prior information into a source model. An algorithm is developed that utilizes information regarding both the statistics of the amplitudes...

  5. Deep Learning and Bayesian Methods

    Directory of Open Access Journals (Sweden)

    Prosper Harrison B.

    2017-01-01

    Full Text Available A revolution is underway in which deep neural networks are routinely used to solve diffcult problems such as face recognition and natural language understanding. Particle physicists have taken notice and have started to deploy these methods, achieving results that suggest a potentially significant shift in how data might be analyzed in the not too distant future. We discuss a few recent developments in the application of deep neural networks and then indulge in speculation about how such methods might be used to automate certain aspects of data analysis in particle physics. Next, the connection to Bayesian methods is discussed and the paper ends with thoughts on a significant practical issue, namely, how, from a Bayesian perspective, one might optimize the construction of deep neural networks.

  6. Bayesian priors for transiting planets

    CERN Document Server

    Kipping, David M

    2016-01-01

    As astronomers push towards discovering ever-smaller transiting planets, it is increasingly common to deal with low signal-to-noise ratio (SNR) events, where the choice of priors plays an influential role in Bayesian inference. In the analysis of exoplanet data, the selection of priors is often treated as a nuisance, with observers typically defaulting to uninformative distributions. Such treatments miss a key strength of the Bayesian framework, especially in the low SNR regime, where even weak a priori information is valuable. When estimating the parameters of a low-SNR transit, two key pieces of information are known: (i) the planet has the correct geometric alignment to transit and (ii) the transit event exhibits sufficient signal-to-noise to have been detected. These represent two forms of observational bias. Accordingly, when fitting transits, the model parameter priors should not follow the intrinsic distributions of said terms, but rather those of both the intrinsic distributions and the observational ...

  7. Bayesian inference on proportional elections.

    Directory of Open Access Journals (Sweden)

    Gabriel Hideki Vatanabe Brunello

    Full Text Available Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software.

  8. Elements of Bayesian experimental design

    Energy Technology Data Exchange (ETDEWEB)

    Sivia, D.S. [Rutherford Appleton Lab., Oxon (United Kingdom)

    1997-09-01

    We consider some elements of the Bayesian approach that are important for optimal experimental design. While the underlying principles used are very general, and are explained in detail in a recent tutorial text, they are applied here to the specific case of characterising the inferential value of different resolution peakshapes. This particular issue was considered earlier by Silver, Sivia and Pynn (1989, 1990a, 1990b), and the following presentation confirms and extends the conclusions of their analysis.

  9. Space Shuttle RTOS Bayesian Network

    Science.gov (United States)

    Morris, A. Terry; Beling, Peter A.

    2001-01-01

    With shrinking budgets and the requirements to increase reliability and operational life of the existing orbiter fleet, NASA has proposed various upgrades for the Space Shuttle that are consistent with national space policy. The cockpit avionics upgrade (CAU), a high priority item, has been selected as the next major upgrade. The primary functions of cockpit avionics include flight control, guidance and navigation, communication, and orbiter landing support. Secondary functions include the provision of operational services for non-avionics systems such as data handling for the payloads and caution and warning alerts to the crew. Recently, a process to selection the optimal commercial-off-the-shelf (COTS) real-time operating system (RTOS) for the CAU was conducted by United Space Alliance (USA) Corporation, which is a joint venture between Boeing and Lockheed Martin, the prime contractor for space shuttle operations. In order to independently assess the RTOS selection, NASA has used the Bayesian network-based scoring methodology described in this paper. Our two-stage methodology addresses the issue of RTOS acceptability by incorporating functional, performance and non-functional software measures related to reliability, interoperability, certifiability, efficiency, correctness, business, legal, product history, cost and life cycle. The first stage of the methodology involves obtaining scores for the various measures using a Bayesian network. The Bayesian network incorporates the causal relationships between the various and often competing measures of interest while also assisting the inherently complex decision analysis process with its ability to reason under uncertainty. The structure and selection of prior probabilities for the network is extracted from experts in the field of real-time operating systems. Scores for the various measures are computed using Bayesian probability. In the second stage, multi-criteria trade-off analyses are performed between the scores

  10. Multiview Bayesian Correlated Component Analysis

    DEFF Research Database (Denmark)

    Kamronn, Simon Due; Poulsen, Andreas Trier; Hansen, Lars Kai

    2015-01-01

    we denote Bayesian correlated component analysis, evaluates favorably against three relevant algorithms in simulated data. A well-established benchmark EEG data set is used to further validate the new model and infer the variability of spatial representations across multiple subjects....... are identical. Here we propose a hierarchical probabilistic model that can infer the level of universality in such multiview data, from completely unrelated representations, corresponding to canonical correlation analysis, to identical representations as in correlated component analysis. This new model, which...

  11. Bayesian analysis for kaon photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Marsainy, T., E-mail: tmart@fisika.ui.ac.id; Mart, T., E-mail: tmart@fisika.ui.ac.id [Department Fisika, FMIPA, Universitas Indonesia, Depok 16424 (Indonesia)

    2014-09-25

    We have investigated contribution of the nucleon resonances in the kaon photoproduction process by using an established statistical decision making method, i.e. the Bayesian method. This method does not only evaluate the model over its entire parameter space, but also takes the prior information and experimental data into account. The result indicates that certain resonances have larger probabilities to contribute to the process.

  12. Bayesian priors and nuisance parameters

    CERN Document Server

    Gupta, Sourendu

    2016-01-01

    Bayesian techniques are widely used to obtain spectral functions from correlators. We suggest a technique to rid the results of nuisance parameters, ie, parameters which are needed for the regularization but cannot be determined from data. We give examples where the method works, including a pion mass extraction with two flavours of staggered quarks at a lattice spacing of about 0.07 fm. We also give an example where the method does not work.

  13. Bayesian kinematic earthquake source models

    Science.gov (United States)

    Minson, S. E.; Simons, M.; Beck, J. L.; Genrich, J. F.; Galetzka, J. E.; Chowdhury, F.; Owen, S. E.; Webb, F.; Comte, D.; Glass, B.; Leiva, C.; Ortega, F. H.

    2009-12-01

    Most coseismic, postseismic, and interseismic slip models are based on highly regularized optimizations which yield one solution which satisfies the data given a particular set of regularizing constraints. This regularization hampers our ability to answer basic questions such as whether seismic and aseismic slip overlap or instead rupture separate portions of the fault zone. We present a Bayesian methodology for generating kinematic earthquake source models with a focus on large subduction zone earthquakes. Unlike classical optimization approaches, Bayesian techniques sample the ensemble of all acceptable models presented as an a posteriori probability density function (PDF), and thus we can explore the entire solution space to determine, for example, which model parameters are well determined and which are not, or what is the likelihood that two slip distributions overlap in space. Bayesian sampling also has the advantage that all a priori knowledge of the source process can be used to mold the a posteriori ensemble of models. Although very powerful, Bayesian methods have up to now been of limited use in geophysical modeling because they are only computationally feasible for problems with a small number of free parameters due to what is called the "curse of dimensionality." However, our methodology can successfully sample solution spaces of many hundreds of parameters, which is sufficient to produce finite fault kinematic earthquake models. Our algorithm is a modification of the tempered Markov chain Monte Carlo (tempered MCMC or TMCMC) method. In our algorithm, we sample a "tempered" a posteriori PDF using many MCMC simulations running in parallel and evolutionary computation in which models which fit the data poorly are preferentially eliminated in favor of models which better predict the data. We present results for both synthetic test problems as well as for the 2007 Mw 7.8 Tocopilla, Chile earthquake, the latter of which is constrained by InSAR, local high

  14. Bayesian Sampling using Condition Indicators

    DEFF Research Database (Denmark)

    Faber, Michael H.; Sørensen, John Dalsgaard

    2002-01-01

    . This allows for a Bayesian formulation of the indicators whereby the experience and expertise of the inspection personnel may be fully utilized and consistently updated as frequentistic information is collected. The approach is illustrated on an example considering a concrete structure subject to corrosion....... It is shown how half-cell potential measurements may be utilized to update the probability of excessive repair after 50 years....

  15. Bayesian second law of thermodynamics.

    Science.gov (United States)

    Bartolotta, Anthony; Carroll, Sean M; Leichenauer, Stefan; Pollack, Jason

    2016-08-01

    We derive a generalization of the second law of thermodynamics that uses Bayesian updates to explicitly incorporate the effects of a measurement of a system at some point in its evolution. By allowing an experimenter's knowledge to be updated by the measurement process, this formulation resolves a tension between the fact that the entropy of a statistical system can sometimes fluctuate downward and the information-theoretic idea that knowledge of a stochastically evolving system degrades over time. The Bayesian second law can be written as ΔH(ρ_{m},ρ)+〈Q〉_{F|m}≥0, where ΔH(ρ_{m},ρ) is the change in the cross entropy between the original phase-space probability distribution ρ and the measurement-updated distribution ρ_{m} and 〈Q〉_{F|m} is the expectation value of a generalized heat flow out of the system. We also derive refined versions of the second law that bound the entropy increase from below by a non-negative number, as well as Bayesian versions of integral fluctuation theorems. We demonstrate the formalism using simple analytical and numerical examples.

  16. Bayesian second law of thermodynamics

    Science.gov (United States)

    Bartolotta, Anthony; Carroll, Sean M.; Leichenauer, Stefan; Pollack, Jason

    2016-08-01

    We derive a generalization of the second law of thermodynamics that uses Bayesian updates to explicitly incorporate the effects of a measurement of a system at some point in its evolution. By allowing an experimenter's knowledge to be updated by the measurement process, this formulation resolves a tension between the fact that the entropy of a statistical system can sometimes fluctuate downward and the information-theoretic idea that knowledge of a stochastically evolving system degrades over time. The Bayesian second law can be written as Δ H (ρm,ρ ) + F |m≥0 , where Δ H (ρm,ρ ) is the change in the cross entropy between the original phase-space probability distribution ρ and the measurement-updated distribution ρm and F |m is the expectation value of a generalized heat flow out of the system. We also derive refined versions of the second law that bound the entropy increase from below by a non-negative number, as well as Bayesian versions of integral fluctuation theorems. We demonstrate the formalism using simple analytical and numerical examples.

  17. Multiple quantitative trait analysis using bayesian networks.

    Science.gov (United States)

    Scutari, Marco; Howell, Phil; Balding, David J; Mackay, Ian

    2014-09-01

    Models for genome-wide prediction and association studies usually target a single phenotypic trait. However, in animal and plant genetics it is common to record information on multiple phenotypes for each individual that will be genotyped. Modeling traits individually disregards the fact that they are most likely associated due to pleiotropy and shared biological basis, thus providing only a partial, confounded view of genetic effects and phenotypic interactions. In this article we use data from a Multiparent Advanced Generation Inter-Cross (MAGIC) winter wheat population to explore Bayesian networks as a convenient and interpretable framework for the simultaneous modeling of multiple quantitative traits. We show that they are equivalent to multivariate genetic best linear unbiased prediction (GBLUP) and that they are competitive with single-trait elastic net and single-trait GBLUP in predictive performance. Finally, we discuss their relationship with other additive-effects models and their advantages in inference and interpretation. MAGIC populations provide an ideal setting for this kind of investigation because the very low population structure and large sample size result in predictive models with good power and limited confounding due to relatedness.

  18. Seeded Bayesian Networks: Constructing genetic networks from microarray data

    Directory of Open Access Journals (Sweden)

    Quackenbush John

    2008-07-01

    Full Text Available Abstract Background DNA microarrays and other genomics-inspired technologies provide large datasets that often include hidden patterns of correlation between genes reflecting the complex processes that underlie cellular metabolism and physiology. The challenge in analyzing large-scale expression data has been to extract biologically meaningful inferences regarding these processes – often represented as networks – in an environment where the datasets are often imperfect and biological noise can obscure the actual signal. Although many techniques have been developed in an attempt to address these issues, to date their ability to extract meaningful and predictive network relationships has been limited. Here we describe a method that draws on prior information about gene-gene interactions to infer biologically relevant pathways from microarray data. Our approach consists of using preliminary networks derived from the literature and/or protein-protein interaction data as seeds for a Bayesian network analysis of microarray results. Results Through a bootstrap analysis of gene expression data derived from a number of leukemia studies, we demonstrate that seeded Bayesian Networks have the ability to identify high-confidence gene-gene interactions which can then be validated by comparison to other sources of pathway data. Conclusion The use of network seeds greatly improves the ability of Bayesian Network analysis to learn gene interaction networks from gene expression data. We demonstrate that the use of seeds derived from the biomedical literature or high-throughput protein-protein interaction data, or the combination, provides improvement over a standard Bayesian Network analysis, allowing networks involving dynamic processes to be deduced from the static snapshots of biological systems that represent the most common source of microarray data. Software implementing these methods has been included in the widely used TM4 microarray analysis package.

  19. 12th Brazilian Meeting on Bayesian Statistics

    CERN Document Server

    Louzada, Francisco; Rifo, Laura; Stern, Julio; Lauretto, Marcelo

    2015-01-01

    Through refereed papers, this volume focuses on the foundations of the Bayesian paradigm; their comparison to objectivistic or frequentist Statistics counterparts; and the appropriate application of Bayesian foundations. This research in Bayesian Statistics is applicable to data analysis in biostatistics, clinical trials, law, engineering, and the social sciences. EBEB, the Brazilian Meeting on Bayesian Statistics, is held every two years by the ISBrA, the International Society for Bayesian Analysis, one of the most active chapters of the ISBA. The 12th meeting took place March 10-14, 2014 in Atibaia. Interest in foundations of inductive Statistics has grown recently in accordance with the increasing availability of Bayesian methodological alternatives. Scientists need to deal with the ever more difficult choice of the optimal method to apply to their problem. This volume shows how Bayes can be the answer. The examination and discussion on the foundations work towards the goal of proper application of Bayesia...

  20. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Chavira, Mark; Darwiche, Adnan

    2004-01-01

    We describe a system for exact inference with relational Bayesian networks as defined in the publicly available \\primula\\ tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference by evaluating...... and differentiating these circuits in time linear in their size. We report on experimental results showing the successful compilation, and efficient inference, on relational Bayesian networks whose {\\primula}--generated propositional instances have thousands of variables, and whose jointrees have clusters...

  1. Anomaly Detection and Attribution Using Bayesian Networks

    Science.gov (United States)

    2014-06-01

    UNCLASSIFIED Anomaly Detection and Attribution Using Bayesian Networks Andrew Kirk, Jonathan Legg and Edwin El-Mahassni National Security and...detection in Bayesian networks , en- abling both the detection and explanation of anomalous cases in a dataset. By exploiting the structure of a... Bayesian network , our algorithm is able to efficiently search for local maxima of data conflict between closely related vari- ables. Benchmark tests using

  2. 3rd Bayesian Young Statisticians Meeting

    CERN Document Server

    Lanzarone, Ettore; Villalobos, Isadora; Mattei, Alessandra

    2017-01-01

    This book is a selection of peer-reviewed contributions presented at the third Bayesian Young Statisticians Meeting, BAYSM 2016, Florence, Italy, June 19-21. The meeting provided a unique opportunity for young researchers, M.S. students, Ph.D. students, and postdocs dealing with Bayesian statistics to connect with the Bayesian community at large, to exchange ideas, and to network with others working in the same field. The contributions develop and apply Bayesian methods in a variety of fields, ranging from the traditional (e.g., biostatistics and reliability) to the most innovative ones (e.g., big data and networks).

  3. SYNTHESIZED EXPECTED BAYESIAN METHOD OF PARAMETRIC ESTIMATE

    Institute of Scientific and Technical Information of China (English)

    Ming HAN; Yuanyao DING

    2004-01-01

    This paper develops a new method of parametric estimate, which is named as "synthesized expected Bayesian method". When samples of products are tested and no failure events occur, thedefinition of expected Bayesian estimate is introduced and the estimates of failure probability and failure rate are provided. After some failure information is introduced by making an extra-test, a synthesized expected Bayesian method is defined and used to estimate failure probability, failure rateand some other parameters in exponential distribution and Weibull distribution of populations. Finally,calculations are performed according to practical problems, which show that the synthesized expected Bayesian method is feasible and easy to operate.

  4. Variational bayesian method of estimating variance components.

    Science.gov (United States)

    Arakawa, Aisaku; Taniguchi, Masaaki; Hayashi, Takeshi; Mikawa, Satoshi

    2016-07-01

    We developed a Bayesian analysis approach by using a variational inference method, a so-called variational Bayesian method, to determine the posterior distributions of variance components. This variational Bayesian method and an alternative Bayesian method using Gibbs sampling were compared in estimating genetic and residual variance components from both simulated data and publically available real pig data. In the simulated data set, we observed strong bias toward overestimation of genetic variance for the variational Bayesian method in the case of low heritability and low population size, and less bias was detected with larger population sizes in both methods examined. The differences in the estimates of variance components between the variational Bayesian and the Gibbs sampling were not found in the real pig data. However, the posterior distributions of the variance components obtained with the variational Bayesian method had shorter tails than those obtained with the Gibbs sampling. Consequently, the posterior standard deviations of the genetic and residual variances of the variational Bayesian method were lower than those of the method using Gibbs sampling. The computing time required was much shorter with the variational Bayesian method than with the method using Gibbs sampling.

  5. Learning dynamic Bayesian networks with mixed variables

    DEFF Research Database (Denmark)

    Bøttcher, Susanne Gammelgaard

    This paper considers dynamic Bayesian networks for discrete and continuous variables. We only treat the case, where the distribution of the variables is conditional Gaussian. We show how to learn the parameters and structure of a dynamic Bayesian network and also how the Markov order can be learn....... An automated procedure for specifying prior distributions for the parameters in a dynamic Bayesian network is presented. It is a simple extension of the procedure for the ordinary Bayesian networks. Finally the W¨olfer?s sunspot numbers are analyzed....

  6. Practical constraints on real time Bayesian filtering for NDE applications

    Science.gov (United States)

    Summan, R.; Pierce, S.; Dobie, G.; Hensman, J.; MacLeod, C.

    2014-01-01

    An experimental evaluation of Bayesian positional filtering algorithms applied to mobile robots for Non-Destructive Evaluation is presented using multiple positional sensing data - a real time, on-robot implementation of an Extended Kalman and Particle filter was used to control a robot performing representative raster scanning of a sample. Both absolute and relative positioning were employed - the absolute being an indoor acoustic GPS system that required careful calibration. The performance of the tracking algorithms are compared in terms of computational cost and the accuracy of trajectory estimates. It is demonstrated that for real time NDE scanning, the Extended Kalman Filter is a more sensible choice given the high computational overhead for the Particle filter.

  7. Lung gallium scan

    Science.gov (United States)

    Gallium 67 lung scan; Lung scan; Gallium scan - lung; Scan - lung ... Gallium is injected into a vein. The scan will be taken 6 to 24 hours after the gallium is injected. (Test time depends on whether your condition is acute or chronic .) ...

  8. Bayesian flood forecasting methods: A review

    Science.gov (United States)

    Han, Shasha; Coulibaly, Paulin

    2017-08-01

    Over the past few decades, floods have been seen as one of the most common and largely distributed natural disasters in the world. If floods could be accurately forecasted in advance, then their negative impacts could be greatly minimized. It is widely recognized that quantification and reduction of uncertainty associated with the hydrologic forecast is of great importance for flood estimation and rational decision making. Bayesian forecasting system (BFS) offers an ideal theoretic framework for uncertainty quantification that can be developed for probabilistic flood forecasting via any deterministic hydrologic model. It provides suitable theoretical structure, empirically validated models and reasonable analytic-numerical computation method, and can be developed into various Bayesian forecasting approaches. This paper presents a comprehensive review on Bayesian forecasting approaches applied in flood forecasting from 1999 till now. The review starts with an overview of fundamentals of BFS and recent advances in BFS, followed with BFS application in river stage forecasting and real-time flood forecasting, then move to a critical analysis by evaluating advantages and limitations of Bayesian forecasting methods and other predictive uncertainty assessment approaches in flood forecasting, and finally discusses the future research direction in Bayesian flood forecasting. Results show that the Bayesian flood forecasting approach is an effective and advanced way for flood estimation, it considers all sources of uncertainties and produces a predictive distribution of the river stage, river discharge or runoff, thus gives more accurate and reliable flood forecasts. Some emerging Bayesian forecasting methods (e.g. ensemble Bayesian forecasting system, Bayesian multi-model combination) were shown to overcome limitations of single model or fixed model weight and effectively reduce predictive uncertainty. In recent years, various Bayesian flood forecasting approaches have been

  9. Bayesian Methods and Universal Darwinism

    Science.gov (United States)

    Campbell, John

    2009-12-01

    Bayesian methods since the time of Laplace have been understood by their practitioners as closely aligned to the scientific method. Indeed a recent Champion of Bayesian methods, E. T. Jaynes, titled his textbook on the subject Probability Theory: the Logic of Science. Many philosophers of science including Karl Popper and Donald Campbell have interpreted the evolution of Science as a Darwinian process consisting of a `copy with selective retention' algorithm abstracted from Darwin's theory of Natural Selection. Arguments are presented for an isomorphism between Bayesian Methods and Darwinian processes. Universal Darwinism, as the term has been developed by Richard Dawkins, Daniel Dennett and Susan Blackmore, is the collection of scientific theories which explain the creation and evolution of their subject matter as due to the Operation of Darwinian processes. These subject matters span the fields of atomic physics, chemistry, biology and the social sciences. The principle of Maximum Entropy states that Systems will evolve to states of highest entropy subject to the constraints of scientific law. This principle may be inverted to provide illumination as to the nature of scientific law. Our best cosmological theories suggest the universe contained much less complexity during the period shortly after the Big Bang than it does at present. The scientific subject matter of atomic physics, chemistry, biology and the social sciences has been created since that time. An explanation is proposed for the existence of this subject matter as due to the evolution of constraints in the form of adaptations imposed on Maximum Entropy. It is argued these adaptations were discovered and instantiated through the Operations of a succession of Darwinian processes.

  10. Bayesian phylogeography finds its roots.

    Directory of Open Access Journals (Sweden)

    Philippe Lemey

    2009-09-01

    Full Text Available As a key factor in endemic and epidemic dynamics, the geographical distribution of viruses has been frequently interpreted in the light of their genetic histories. Unfortunately, inference of historical dispersal or migration patterns of viruses has mainly been restricted to model-free heuristic approaches that provide little insight into the temporal setting of the spatial dynamics. The introduction of probabilistic models of evolution, however, offers unique opportunities to engage in this statistical endeavor. Here we introduce a Bayesian framework for inference, visualization and hypothesis testing of phylogeographic history. By implementing character mapping in a Bayesian software that samples time-scaled phylogenies, we enable the reconstruction of timed viral dispersal patterns while accommodating phylogenetic uncertainty. Standard Markov model inference is extended with a stochastic search variable selection procedure that identifies the parsimonious descriptions of the diffusion process. In addition, we propose priors that can incorporate geographical sampling distributions or characterize alternative hypotheses about the spatial dynamics. To visualize the spatial and temporal information, we summarize inferences using virtual globe software. We describe how Bayesian phylogeography compares with previous parsimony analysis in the investigation of the influenza A H5N1 origin and H5N1 epidemiological linkage among sampling localities. Analysis of rabies in West African dog populations reveals how virus diffusion may enable endemic maintenance through continuous epidemic cycles. From these analyses, we conclude that our phylogeographic framework will make an important asset in molecular epidemiology that can be easily generalized to infer biogeogeography from genetic data for many organisms.

  11. CGBayesNets: conditional Gaussian Bayesian network learning and inference with mixed discrete and continuous data.

    Science.gov (United States)

    McGeachie, Michael J; Chang, Hsun-Hsien; Weiss, Scott T

    2014-06-01

    Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com.

  12. CGBayesNets: conditional Gaussian Bayesian network learning and inference with mixed discrete and continuous data.

    Directory of Open Access Journals (Sweden)

    Michael J McGeachie

    2014-06-01

    Full Text Available Bayesian Networks (BN have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com.

  13. Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models.

    Science.gov (United States)

    Zucknick, Manuela; Saadati, Maral; Benner, Axel

    2015-11-01

    One important task in translational cancer research is the search for new prognostic biomarkers to improve survival prognosis for patients. The use of high-throughput technologies allows simultaneous measurement of genome-wide gene expression or other genomic data for all patients in a clinical trial. Penalized likelihood methods such as lasso regression can be applied to such high-dimensional data, where the number of (genomic) covariables is usually much larger than the sample size. There is a connection between the lasso and the Bayesian regression model with independent Laplace priors on the regression parameters, and understanding this connection has been useful for understanding the properties of lasso estimates in linear models (e.g. Park and Casella, 2008). In this paper, we study the lasso in the frequentist and Bayesian frameworks in the context of Cox models. For the Bayesian lasso we extend the approach by Lee et al. (2011). In particular, we impose the lasso penalty only on the genome features, but not on relevant clinical covariates, to allow the mandatory inclusion of important established factors. We investigate the models in high- and low-dimensional simulation settings and in an application to chronic lymphocytic leukemia.

  14. Bayesian homeopathy: talking normal again.

    Science.gov (United States)

    Rutten, A L B

    2007-04-01

    Homeopathy has a communication problem: important homeopathic concepts are not understood by conventional colleagues. Homeopathic terminology seems to be comprehensible only after practical experience of homeopathy. The main problem lies in different handling of diagnosis. In conventional medicine diagnosis is the starting point for randomised controlled trials to determine the effect of treatment. In homeopathy diagnosis is combined with other symptoms and personal traits of the patient to guide treatment and predict response. Broadening our scope to include diagnostic as well as treatment research opens the possibility of multi factorial reasoning. Adopting Bayesian methodology opens the possibility of investigating homeopathy in everyday practice and of describing some aspects of homeopathy in conventional terms.

  15. Approximation for Bayesian Ability Estimation.

    Science.gov (United States)

    1987-02-18

    posterior pdfs of ande are given by p(-[Y) p(F) F P((y lei’ j)P )d. SiiJ i (4) a r~d p(e Iy) - p(t0) 1 J i P(Yij ei, (5) As shown in Tsutakawa and Lin...inverse A Hessian of the log of (27) with respect to , evaulatedat a Then, under regularity conditions, the marginal posterior pdf of O is...two-way contingency tables. Journal of Educational Statistics, 11, 33-56. Lindley, D.V. (1980). Approximate Bayesian methods. Trabajos Estadistica , 31

  16. Bayesian Query-Focused Summarization

    CERN Document Server

    Daumé, Hal

    2009-01-01

    We present BayeSum (for ``Bayesian summarization''), a model for sentence extraction in query-focused summarization. BayeSum leverages the common case in which multiple documents are relevant to a single query. Using these documents as reinforcement for query terms, BayeSum is not afflicted by the paucity of information in short queries. We show that approximate inference in BayeSum is possible on large data sets and results in a state-of-the-art summarization system. Furthermore, we show how BayeSum can be understood as a justified query expansion technique in the language modeling for IR framework.

  17. Bayesian tests of measurement invariance.

    Science.gov (United States)

    Verhagen, A J; Fox, J P

    2013-11-01

    Random item effects models provide a natural framework for the exploration of violations of measurement invariance without the need for anchor items. Within the random item effects modelling framework, Bayesian tests (Bayes factor, deviance information criterion) are proposed which enable multiple marginal invariance hypotheses to be tested simultaneously. The performance of the tests is evaluated with a simulation study which shows that the tests have high power and low Type I error rate. Data from the European Social Survey are used to test for measurement invariance of attitude towards immigrant items and to show that background information can be used to explain cross-national variation in item functioning.

  18. Numeracy, frequency, and Bayesian reasoning

    Directory of Open Access Journals (Sweden)

    Gretchen B. Chapman

    2009-02-01

    Full Text Available Previous research has demonstrated that Bayesian reasoning performance is improved if uncertainty information is presented as natural frequencies rather than single-event probabilities. A questionnaire study of 342 college students replicated this effect but also found that the performance-boosting benefits of the natural frequency presentation occurred primarily for participants who scored high in numeracy. This finding suggests that even comprehension and manipulation of natural frequencies requires a certain threshold of numeracy abilities, and that the beneficial effects of natural frequency presentation may not be as general as previously believed.

  19. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan ... tissues in your body. top of page How is the procedure performed? Nuclear medicine imaging is usually ...

  20. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... code: Phone no: Thank you! Do you have a personal story about radiology? Share your patient story ...

  1. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  2. Modeling Diagnostic Assessments with Bayesian Networks

    Science.gov (United States)

    Almond, Russell G.; DiBello, Louis V.; Moulder, Brad; Zapata-Rivera, Juan-Diego

    2007-01-01

    This paper defines Bayesian network models and examines their applications to IRT-based cognitive diagnostic modeling. These models are especially suited to building inference engines designed to be synchronous with the finer grained student models that arise in skills diagnostic assessment. Aspects of the theory and use of Bayesian network models…

  3. Using Bayesian Networks to Improve Knowledge Assessment

    Science.gov (United States)

    Millan, Eva; Descalco, Luis; Castillo, Gladys; Oliveira, Paula; Diogo, Sandra

    2013-01-01

    In this paper, we describe the integration and evaluation of an existing generic Bayesian student model (GBSM) into an existing computerized testing system within the Mathematics Education Project (PmatE--Projecto Matematica Ensino) of the University of Aveiro. This generic Bayesian student model had been previously evaluated with simulated…

  4. Nonparametric Bayesian Modeling of Complex Networks

    DEFF Research Database (Denmark)

    Schmidt, Mikkel Nørgaard; Mørup, Morten

    2013-01-01

    Modeling structure in complex networks using Bayesian nonparametrics makes it possible to specify flexible model structures and infer the adequate model complexity from the observed data. This article provides a gentle introduction to nonparametric Bayesian modeling of complex networks: Using...... for complex networks can be derived and point out relevant literature....

  5. Bayesian analysis of exoplanet and binary orbits

    OpenAIRE

    Schulze-Hartung, Tim; Launhardt, Ralf; Henning, Thomas

    2012-01-01

    We introduce BASE (Bayesian astrometric and spectroscopic exoplanet detection and characterisation tool), a novel program for the combined or separate Bayesian analysis of astrometric and radial-velocity measurements of potential exoplanet hosts and binary stars. The capabilities of BASE are demonstrated using all publicly available data of the binary Mizar A.

  6. Modeling Diagnostic Assessments with Bayesian Networks

    Science.gov (United States)

    Almond, Russell G.; DiBello, Louis V.; Moulder, Brad; Zapata-Rivera, Juan-Diego

    2007-01-01

    This paper defines Bayesian network models and examines their applications to IRT-based cognitive diagnostic modeling. These models are especially suited to building inference engines designed to be synchronous with the finer grained student models that arise in skills diagnostic assessment. Aspects of the theory and use of Bayesian network models…

  7. Bayesian Decision Theoretical Framework for Clustering

    Science.gov (United States)

    Chen, Mo

    2011-01-01

    In this thesis, we establish a novel probabilistic framework for the data clustering problem from the perspective of Bayesian decision theory. The Bayesian decision theory view justifies the important questions: what is a cluster and what a clustering algorithm should optimize. We prove that the spectral clustering (to be specific, the…

  8. Computational Advances for and from Bayesian Analysis

    OpenAIRE

    Andrieu, C.; Doucet, A.; Robert, C. P.

    2004-01-01

    The emergence in the past years of Bayesian analysis in many methodological and applied fields as the solution to the modeling of complex problems cannot be dissociated from major changes in its computational implementation. We show in this review how the advances in Bayesian analysis and statistical computation are intermingled.

  9. Particle identification in ALICE: a Bayesian approach

    NARCIS (Netherlands)

    Adam, J.; Adamova, D.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Almaraz, J. R. M.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Anticic, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Balasubramanian, S.; Baldisseri, A.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnafoeldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Barth, K.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Bathen, B.; Batigne, G.; Camejo, A. Batista; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.; Behera, N. K.; Belikov, I.; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Belmont, R.; Belmont-Moreno, E.; Belyaev, V.; Benacek, P.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Bjelogrlic, S.; Blair, J. T.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Boggild, H.; Boldizsar, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossu, F.; Botta, E.; Bourjau, C.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Cabala, J.; Caffarri, D.; Cai, X.; Caines, H.; Diaz, L. Calero; Caliva, A.; Calvo Villar, E.; Camerini, P.; Carena, F.; Carena, W.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Cepila, J.; Cerello, P.; Cerkala, J.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chauvin, A.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Choi, K.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortes Maldonado, I.; Cortese, P.; Cosentino, M. R.; Costa, F.; Crochet, P.; Cruz Albino, R.; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danisch, M. C.; Danu, A.; Das, I.; Das, S.; Dash, A.; Dash, S.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; Deisting, A.; Deloff, A.; Denes, E.; Deplano, C.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Di Nezza, P.; Corchero, M. A. Diaz; Dietel, T.; Dillenseger, P.; Divia, R.; Djuvsland, O.; Dobrin, A.; Gimenez, D. Domenicis; Doenigus, B.; Dordic, O.; Drozhzhova, T.; Dubey, A. K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Endress, E.; Engel, H.; Epple, E.; Erazmus, B.; Erdemir, I.; Erhardt, F.; Espagnon, B.; Estienne, M.; Esumi, S.; Eum, J.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernandez Tellez, A.; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Fleck, M. G.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gallio, M.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-Solis, E.; Gargiulo, C.; Gasik, P.; Gauger, E. F.; Germain, M.; Gheata, A.; Gheata, M.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-Dziadus, E.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, A. S.; Gonzalez, V.; Gonzalez-Zamora, P.; Gorbunov, S.; Goerlich, L.; Gotovac, S.; Grabski, V.; Grachov, O. A.; Graczykowski, L. K.; Graham, K. L.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Gronefeld, J. M.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Haake, R.; Haaland, O.

    2016-01-01

    We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian

  10. Bayesian credible interval construction for Poisson statistics

    Institute of Scientific and Technical Information of China (English)

    ZHU Yong-Sheng

    2008-01-01

    The construction of the Bayesian credible (confidence) interval for a Poisson observable including both the signal and background with and without systematic uncertainties is presented.Introducing the conditional probability satisfying the requirement of the background not larger than the observed events to construct the Bayesian credible interval is also discussed.A Fortran routine,BPOCI,has been developed to implement the calculation.

  11. Using Bayesian Networks to Improve Knowledge Assessment

    Science.gov (United States)

    Millan, Eva; Descalco, Luis; Castillo, Gladys; Oliveira, Paula; Diogo, Sandra

    2013-01-01

    In this paper, we describe the integration and evaluation of an existing generic Bayesian student model (GBSM) into an existing computerized testing system within the Mathematics Education Project (PmatE--Projecto Matematica Ensino) of the University of Aveiro. This generic Bayesian student model had been previously evaluated with simulated…

  12. The Bayesian Revolution Approaches Psychological Development

    Science.gov (United States)

    Shultz, Thomas R.

    2007-01-01

    This commentary reviews five articles that apply Bayesian ideas to psychological development, some with psychology experiments, some with computational modeling, and some with both experiments and modeling. The reviewed work extends the current Bayesian revolution into tasks often studied in children, such as causal learning and word learning, and…

  13. Advances in Bayesian Modeling in Educational Research

    Science.gov (United States)

    Levy, Roy

    2016-01-01

    In this article, I provide a conceptually oriented overview of Bayesian approaches to statistical inference and contrast them with frequentist approaches that currently dominate conventional practice in educational research. The features and advantages of Bayesian approaches are illustrated with examples spanning several statistical modeling…

  14. Bayesian Network for multiple hypthesis tracking

    NARCIS (Netherlands)

    W.P. Zajdel; B.J.A. Kröse

    2002-01-01

    For a flexible camera-to-camera tracking of multiple objects we model the objects behavior with a Bayesian network and combine it with the multiple hypohesis framework that associates observations with objects. Bayesian networks offer a possibility to factor complex, joint distributions into a produ

  15. Bayesian Statistics for Biological Data: Pedigree Analysis

    Science.gov (United States)

    Stanfield, William D.; Carlton, Matthew A.

    2004-01-01

    The use of Bayes' formula is applied to the biological problem of pedigree analysis to show that the Bayes' formula and non-Bayesian or "classical" methods of probability calculation give different answers. First year college students of biology can be introduced to the Bayesian statistics.

  16. Genomics and Health Impact Update

    Science.gov (United States)

    ... Comparative Effectiveness Developmental Disabilities Liquid Biopsy Lung Cancer Microbiome Nutrigenomics Sudden Death Impact Scan CDC Publications Birth Defects/ Child Health Cancer Cardiovascular Diseases Chronic Disease Ethics, Policy and Law Genomics in ...

  17. Evaluation of logistic Bayesian LASSO for identifying association with rare haplotypes.

    Science.gov (United States)

    Biswas, Swati; Papachristou, Charalampos

    2014-01-01

    It has been hypothesized that rare variants may hold the key to unraveling the genetic transmission mechanism of many common complex traits. Currently, there is a dearth of statistical methods that are powerful enough to detect association with rare haplotypes. One of the recently proposed methods is logistic Bayesian LASSO for case-control data. By penalizing the regression coefficients through appropriate priors, logistic Bayesian LASSO weeds out the unassociated haplotypes, making it possible for the associated rare haplotypes to be detected with higher powers. We used the Genetic Analysis Workshop 18 simulated data to evaluate the behavior of logistic Bayesian LASSO in terms of its power and type I error under a complex disease model. We obtained knowledge of the simulation model, including the locations of the functional variants, and we chose to focus on two genomic regions in the MAP4 gene on chromosome 3. The sample size was 142 individuals and there were 200 replicates. Despite the small sample size, logistic Bayesian LASSO showed high power to detect two haplotypes containing functional variants in these regions while maintaining low type I errors. At the same time, a commonly used approach for haplotype association implemented in the software hapassoc failed to converge because of the presence of rare haplotypes. Thus, we conclude that logistic Bayesian LASSO can play an important role in the search for rare haplotypes.

  18. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  19. Hepatitis disease detection using Bayesian theory

    Science.gov (United States)

    Maseleno, Andino; Hidayati, Rohmah Zahroh

    2017-02-01

    This paper presents hepatitis disease diagnosis using a Bayesian theory for better understanding of the theory. In this research, we used a Bayesian theory for detecting hepatitis disease and displaying the result of diagnosis process. Bayesian algorithm theory is rediscovered and perfected by Laplace, the basic idea is using of the known prior probability and conditional probability density parameter, based on Bayes theorem to calculate the corresponding posterior probability, and then obtained the posterior probability to infer and make decisions. Bayesian methods combine existing knowledge, prior probabilities, with additional knowledge derived from new data, the likelihood function. The initial symptoms of hepatitis which include malaise, fever and headache. The probability of hepatitis given the presence of malaise, fever, and headache. The result revealed that a Bayesian theory has successfully identified the existence of hepatitis disease.

  20. Bayesian natural language semantics and pragmatics

    CERN Document Server

    Zeevat, Henk

    2015-01-01

    The contributions in this volume focus on the Bayesian interpretation of natural languages, which is widely used in areas of artificial intelligence, cognitive science, and computational linguistics. This is the first volume to take up topics in Bayesian Natural Language Interpretation and make proposals based on information theory, probability theory, and related fields. The methodologies offered here extend to the target semantic and pragmatic analyses of computational natural language interpretation. Bayesian approaches to natural language semantics and pragmatics are based on methods from signal processing and the causal Bayesian models pioneered by especially Pearl. In signal processing, the Bayesian method finds the most probable interpretation by finding the one that maximizes the product of the prior probability and the likelihood of the interpretation. It thus stresses the importance of a production model for interpretation as in Grice's contributions to pragmatics or in interpretation by abduction.

  1. 2nd Bayesian Young Statisticians Meeting

    CERN Document Server

    Bitto, Angela; Kastner, Gregor; Posekany, Alexandra

    2015-01-01

    The Second Bayesian Young Statisticians Meeting (BAYSM 2014) and the research presented here facilitate connections among researchers using Bayesian Statistics by providing a forum for the development and exchange of ideas. WU Vienna University of Business and Economics hosted BAYSM 2014 from September 18th to 19th. The guidance of renowned plenary lecturers and senior discussants is a critical part of the meeting and this volume, which follows publication of contributions from BAYSM 2013. The meeting's scientific program reflected the variety of fields in which Bayesian methods are currently employed or could be introduced in the future. Three brilliant keynote lectures by Chris Holmes (University of Oxford), Christian Robert (Université Paris-Dauphine), and Mike West (Duke University), were complemented by 24 plenary talks covering the major topics Dynamic Models, Applications, Bayesian Nonparametrics, Biostatistics, Bayesian Methods in Economics, and Models and Methods, as well as a lively poster session ...

  2. Scan BIST with biased scan test signals

    Institute of Scientific and Technical Information of China (English)

    XIANG Dong; CHEN MingJing; SUN JiaGuang

    2008-01-01

    The conventional test-per-scan built-in self-test (BIST) scheme needs a number of shift cycles followed by one capture cycle.Fault effects received by the scan flip-flops are shifted out while shifting in the next test vector like scan testing.Unlike deterministic testing,it is unnecessary to apply a complete test vector to the scan chains.A new scan-based BIST scheme is proposed by properly controlling the test signals of the scan chains,Different biased random values are assigned to the test signals of scan flip-flops in separate scan chains.Capture cycles can be inserted at any clock cycle if necessary.A new testability estimation procedure according to the proposed testing scheme is presented.A greedy procedure is proposed to select a weight for each scan chain.Experimental results show that the proposed method can improve test effectiveness of scan-based BIST greatly,and most circuits can obtain complete fault coverage or very close to complete fault coverage.

  3. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  4. Bayesian modeling in conjoint analysis

    Directory of Open Access Journals (Sweden)

    Janković-Milić Vesna

    2010-01-01

    Full Text Available Statistical analysis in marketing is largely influenced by the availability of various types of data. There is sudden increase in the number and types of information available to market researchers in the last decade. In such conditions, traditional statistical methods have limited ability to solve problems related to the expression of market uncertainty. The aim of this paper is to highlight the advantages of bayesian inference, as an alternative approach to classical inference. Multivariate statistic methods offer extremely powerful tools to achieve many goals of marketing research. One of these methods is the conjoint analysis, which provides a quantitative measure of the relative importance of product or service attributes in relation to the other attribute. The application of this method involves interviewing consumers, where they express their preferences, and statistical analysis provides numerical indicators of each attribute utility. One of the main objections to the method of discrete choice in the conjoint analysis is to use this method to estimate the utility only at the aggregate level and by expressing the average utility for all respondents in the survey. Application of hierarchical Bayesian models enables capturing of individual utility ratings for each attribute level.

  5. Bayesian Reconstruction of the Velocity Distribution of Weakly Interacting Massive Particles from Direct Dark Matter Detection Data

    CERN Document Server

    Shan, Chung-Lin

    2014-01-01

    In this paper, we extended our earlier work on the reconstruction of the (time-averaged) one-dimensional velocity distribution of Galactic Weakly Interacting Massive Particles (WIMPs) and introduce the Bayesian fitting procedure to the theoretically predicted velocity distribution functions. In this reconstruction process, the (rough) velocity distribution reconstructed by using raw data from direct Dark Matter detection experiments directly, i.e. measured recoil energies, with one or more different target materials, has been used as "reconstructed-input" information. By assuming a fitting velocity distribution function and scanning the parameter space based on the Bayesian analysis, the astronomical characteristic parameters, e.g. the Solar and Earth's orbital velocities, will be pinned down as the output results. Our Monte-Carlo simulations show that this Bayesian scanning procedure could reconstruct the true (input) WIMP velocity distribution function pretty precisely with negligible systematic deviations ...

  6. Bayesian Computation Methods for Inferring Regulatory Network Models Using Biomedical Data.

    Science.gov (United States)

    Tian, Tianhai

    2016-01-01

    The rapid advancement of high-throughput technologies provides huge amounts of information for gene expression and protein activity in the genome-wide scale. The availability of genomics, transcriptomics, proteomics, and metabolomics dataset gives an unprecedented opportunity to study detailed molecular regulations that is very important to precision medicine. However, it is still a significant challenge to design effective and efficient method to infer the network structure and dynamic property of regulatory networks. In recent years a number of computing methods have been designed to explore the regulatory mechanisms as well as estimate unknown model parameters. Among them, the Bayesian inference method can combine both prior knowledge and experimental data to generate updated information regarding the regulatory mechanisms. This chapter gives a brief review for Bayesian statistical methods that are used to infer the network structure and estimate model parameters based on experimental data.

  7. Bayesian approach to noninferiority trials for proportions.

    Science.gov (United States)

    Gamalo, Mark A; Wu, Rui; Tiwari, Ram C

    2011-09-01

    Noninferiority trials are unique because they are dependent upon historical information in order to make meaningful interpretation of their results. Hence, a direct application of the Bayesian paradigm in sequential learning becomes apparently useful in the analysis. This paper describes a Bayesian procedure for testing noninferiority in two-arm studies with a binary primary endpoint that allows the incorporation of historical data on an active control via the use of informative priors. In particular, the posteriors of the response in historical trials are assumed as priors for its corresponding parameters in the current trial, where that treatment serves as the active control. The Bayesian procedure includes a fully Bayesian method and two normal approximation methods on the prior and/or on the posterior distributions. Then a common Bayesian decision criterion is used but with two prespecified cutoff levels, one for the approximation methods and the other for the fully Bayesian method, to determine whether the experimental treatment is noninferior to the active control. This criterion is evaluated and compared with the frequentist method using simulation studies in keeping with regulatory framework that new methods must protect type I error and arrive at a similar conclusion with existing standard strategies. Results show that both methods arrive at comparable conclusions of noninferiority when applied to a modified real data set. The advantage of the proposed Bayesian approach lies in its ability to provide posterior probabilities for effect sizes of the experimental treatment over the active control.

  8. Conventional cerebrospinal fluid scanning

    Energy Technology Data Exchange (ETDEWEB)

    Schicha, H.

    1985-06-01

    Conventional cerebrospinal fluid scanning (CSF scanning) today is mainly carried out in addition to computerized tomography to obtain information about liquor flow kinetics. Especially in patients with communicating obstructive hydrocephalus, CSF scanning is clinically useful for the decision for shunt surgery. In patients with intracranial cysts, CSF scanning can provide information about liquor circulation. Further indications for CSF scanning include the assessment of shunt patency especially in children, as well as the detection and localization of cerebrospinal fluid leaks.

  9. Bayesian networks in educational assessment

    CERN Document Server

    Almond, Russell G; Steinberg, Linda S; Yan, Duanli; Williamson, David M

    2015-01-01

    Bayesian inference networks, a synthesis of statistics and expert systems, have advanced reasoning under uncertainty in medicine, business, and social sciences. This innovative volume is the first comprehensive treatment exploring how they can be applied to design and analyze innovative educational assessments. Part I develops Bayes nets’ foundations in assessment, statistics, and graph theory, and works through the real-time updating algorithm. Part II addresses parametric forms for use with assessment, model-checking techniques, and estimation with the EM algorithm and Markov chain Monte Carlo (MCMC). A unique feature is the volume’s grounding in Evidence-Centered Design (ECD) framework for assessment design. This “design forward” approach enables designers to take full advantage of Bayes nets’ modularity and ability to model complex evidentiary relationships that arise from performance in interactive, technology-rich assessments such as simulations. Part III describes ECD, situates Bayes nets as ...

  10. Bayesian anti-sparse coding

    CERN Document Server

    Elvira, Clément; Dobigeon, Nicolas

    2015-01-01

    Sparse representations have proven their efficiency in solving a wide class of inverse problems encountered in signal and image processing. Conversely, enforcing the information to be spread uniformly over representation coefficients exhibits relevant properties in various applications such as digital communications. Anti-sparse regularization can be naturally expressed through an $\\ell_{\\infty}$-norm penalty. This paper derives a probabilistic formulation of such representations. A new probability distribution, referred to as the democratic prior, is first introduced. Its main properties as well as three random variate generators for this distribution are derived. Then this probability distribution is used as a prior to promote anti-sparsity in a Gaussian linear inverse problem, yielding a fully Bayesian formulation of anti-sparse coding. Two Markov chain Monte Carlo (MCMC) algorithms are proposed to generate samples according to the posterior distribution. The first one is a standard Gibbs sampler. The seco...

  11. On Bayesian System Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen Ringi, M.

    1995-05-01

    The view taken in this thesis is that reliability, the probability that a system will perform a required function for a stated period of time, depends on a person`s state of knowledge. Reliability changes as this state of knowledge changes, i.e. when new relevant information becomes available. Most existing models for system reliability prediction are developed in a classical framework of probability theory and they overlook some information that is always present. Probability is just an analytical tool to handle uncertainty, based on judgement and subjective opinions. It is argued that the Bayesian approach gives a much more comprehensive understanding of the foundations of probability than the so called frequentistic school. A new model for system reliability prediction is given in two papers. The model encloses the fact that component failures are dependent because of a shared operational environment. The suggested model also naturally permits learning from failure data of similar components in non identical environments. 85 refs.

  12. Quantum Bayesianism at the Perimeter

    CERN Document Server

    Fuchs, Christopher A

    2010-01-01

    The author summarizes the Quantum Bayesian viewpoint of quantum mechanics, developed originally by C. M. Caves, R. Schack, and himself. It is a view crucially dependent upon the tools of quantum information theory. Work at the Perimeter Institute for Theoretical Physics continues the development and is focused on the hard technical problem of a finding a good representation of quantum mechanics purely in terms of probabilities, without amplitudes or Hilbert-space operators. The best candidate representation involves a mysterious entity called a symmetric informationally complete quantum measurement. Contemplation of it gives a way of thinking of the Born Rule as an addition to the rules of probability theory, applicable when one gambles on the consequences of interactions with physical systems. The article ends by outlining some directions for future work.

  13. Hedging Strategies for Bayesian Optimization

    CERN Document Server

    Brochu, Eric; de Freitas, Nando

    2010-01-01

    Bayesian optimization with Gaussian processes has become an increasingly popular tool in the machine learning community. It is efficient and can be used when very little is known about the objective function, making it popular in expensive black-box optimization scenarios. It is able to do this by sampling the objective using an acquisition function which incorporates the model's estimate of the objective and the uncertainty at any given point. However, there are several different parameterized acquisition functions in the literature, and it is often unclear which one to use. Instead of using a single acquisition function, we adopt a portfolio of acquisition functions governed by an online multi-armed bandit strategy. We describe the method, which we call GP-Hedge, and show that this method almost always outperforms the best individual acquisition function.

  14. Bayesian Inference with Optimal Maps

    CERN Document Server

    Moselhy, Tarek A El

    2011-01-01

    We present a new approach to Bayesian inference that entirely avoids Markov chain simulation, by constructing a map that pushes forward the prior measure to the posterior measure. Existence and uniqueness of a suitable measure-preserving map is established by formulating the problem in the context of optimal transport theory. We discuss various means of explicitly parameterizing the map and computing it efficiently through solution of an optimization problem, exploiting gradient information from the forward model when possible. The resulting algorithm overcomes many of the computational bottlenecks associated with Markov chain Monte Carlo. Advantages of a map-based representation of the posterior include analytical expressions for posterior moments and the ability to generate arbitrary numbers of independent posterior samples without additional likelihood evaluations or forward solves. The optimization approach also provides clear convergence criteria for posterior approximation and facilitates model selectio...

  15. Bayesian Approach to Inverse Problems

    CERN Document Server

    2008-01-01

    Many scientific, medical or engineering problems raise the issue of recovering some physical quantities from indirect measurements; for instance, detecting or quantifying flaws or cracks within a material from acoustic or electromagnetic measurements at its surface is an essential problem of non-destructive evaluation. The concept of inverse problems precisely originates from the idea of inverting the laws of physics to recover a quantity of interest from measurable data.Unfortunately, most inverse problems are ill-posed, which means that precise and stable solutions are not easy to devise. Regularization is the key concept to solve inverse problems.The goal of this book is to deal with inverse problems and regularized solutions using the Bayesian statistical tools, with a particular view to signal and image estimation

  16. Bayesian Inference in Queueing Networks

    CERN Document Server

    Sutton, Charles

    2010-01-01

    Modern Web services, such as those at Google, Yahoo!, and Amazon, handle billions of requests per day on clusters of thousands of computers. Because these services operate under strict performance requirements, a statistical understanding of their performance is of great practical interest. Such services are modeled by networks of queues, where one queue models each of the individual computers in the system. A key challenge is that the data is incomplete, because recording detailed information about every request to a heavily used system can require unacceptable overhead. In this paper we develop a Bayesian perspective on queueing models in which the arrival and departure times that are not observed are treated as latent variables. Underlying this viewpoint is the observation that a queueing model defines a deterministic transformation between the data and a set of independent variables called the service times. With this viewpoint in hand, we sample from the posterior distribution over missing data and model...

  17. A Bayesian Reflection on Surfaces

    Directory of Open Access Journals (Sweden)

    David R. Wolf

    1999-10-01

    Full Text Available Abstract: The topic of this paper is a novel Bayesian continuous-basis field representation and inference framework. Within this paper several problems are solved: The maximally informative inference of continuous-basis fields, that is where the basis for the field is itself a continuous object and not representable in a finite manner; the tradeoff between accuracy of representation in terms of information learned, and memory or storage capacity in bits; the approximation of probability distributions so that a maximal amount of information about the object being inferred is preserved; an information theoretic justification for multigrid methodology. The maximally informative field inference framework is described in full generality and denoted the Generalized Kalman Filter. The Generalized Kalman Filter allows the update of field knowledge from previous knowledge at any scale, and new data, to new knowledge at any other scale. An application example instance, the inference of continuous surfaces from measurements (for example, camera image data, is presented.

  18. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Darwiche, Adnan; Chavira, Mark

    2006-01-01

    We describe in this paper a system for exact inference with relational Bayesian networks as defined in the publicly available PRIMULA tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference...... by evaluating and differentiating these circuits in time linear in their size. We report on experimental results showing successful compilation and efficient inference on relational Bayesian networks, whose PRIMULA--generated propositional instances have thousands of variables, and whose jointrees have clusters...

  19. Bayesian models a statistical primer for ecologists

    CERN Document Server

    Hobbs, N Thompson

    2015-01-01

    Bayesian modeling has become an indispensable tool for ecological research because it is uniquely suited to deal with complexity in a statistically coherent way. This textbook provides a comprehensive and accessible introduction to the latest Bayesian methods-in language ecologists can understand. Unlike other books on the subject, this one emphasizes the principles behind the computations, giving ecologists a big-picture understanding of how to implement this powerful statistical approach. Bayesian Models is an essential primer for non-statisticians. It begins with a definition of probabili

  20. The Diagnosis of Reciprocating Machinery by Bayesian Networks

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A Bayesian Network is a reasoning tool based on probability theory and has many advantages that other reasoning tools do not have. This paper discusses the basic theory of Bayesian networks and studies the problems in constructing Bayesian networks. The paper also constructs a Bayesian diagnosis network of a reciprocating compressor. The example helps us to draw a conclusion that Bayesian diagnosis networks can diagnose reciprocating machinery effectively.

  1. Genomic signals of diversification along ecological gradients in a tropical lizard.

    Science.gov (United States)

    Freedman, Adam H; Thomassen, Henri A; Buermann, Wolfgang; Smith, Thomas B

    2010-09-01

    Studies of rainforest diversification that simultaneously consider the effects of genetic drift and natural selection are rare. We use Amplified Fragment Length Polymorphism genome scans of the African rainforest lizard Trachylepis affinis from Cameroon to examine the spatial patterns and environmental associations of both neutrally evolving loci and those thought to be under selection. Bayesian selection scans revealed that approximately 7% of the genome may be under divergent selection. Using non-linear environmental modelling techniques, we fit patterns of genetic differentiation recovered from the pooled neutral data and from individual loci showing a signature of natural selection. Neutral differentiation occurred along a cline from coastal lowland rainforest inland toward the gallery forests-savanna mosaic (ecotone), and was associated with both geographic distance and changing precipitation patterns. Loci under selection were differentiated predominantly along the forest-ecotone gradient-in concordance with morphological divergence in traits related to fitness. A second set of these loci was differentiated between lowland and montane habitats. A third set of loci was indicative of divergent selection between rainforest refugia. Niche models and demographic signals in mitochondrial sequence data support a population expansion out of a core rainforest area into savanna since the last glacial maximum. Our findings indicate adaptive diversification in T. affinis may be taking place along the forest-ecotone gradient during range expansions or contractions, and that refugial isolation augmented by divergent adaptation to different rainforest environments appears to play a less significant role.

  2. Correction for Measurement Error from Genotyping-by-Sequencing in Genomic Variance and Genomic Prediction Models

    DEFF Research Database (Denmark)

    Ashraf, Bilal; Janss, Luc; Jensen, Just

    Genotyping-by-sequencing (GBSeq) is becoming a cost-effective genotyping platform for species without available SNP arrays. GBSeq considers to sequence short reads from restriction sites covering a limited part of the genome (e.g., 5-10%) with low sequencing depth per individual (e.g., 5-10X per....... In the current work we show how the correction for measurement error in GBSeq can also be applied in whole genome genomic variance and genomic prediction models. Bayesian whole-genome random regression models are proposed to allow implementation of large-scale SNP-based models with a per-SNP correction...... for measurement error. We show correct retrieval of genomic explained variance, and improved genomic prediction when accounting for the measurement error in GBSeq data...

  3. A Variational Bayes Genomic-Enabled Prediction Model with Genotype × Environment Interaction

    Directory of Open Access Journals (Sweden)

    Osval A. Montesinos-López

    2017-06-01

    Full Text Available There are Bayesian and non-Bayesian genomic models that take into account G×E interactions. However, the computational cost of implementing Bayesian models is high, and becomes almost impossible when the number of genotypes, environments, and traits is very large, while, in non-Bayesian models, there are often important and unsolved convergence problems. The variational Bayes method is popular in machine learning, and, by approximating the probability distributions through optimization, it tends to be faster than Markov Chain Monte Carlo methods. For this reason, in this paper, we propose a new genomic variational Bayes version of the Bayesian genomic model with G×E using half-t priors on each standard deviation (SD term to guarantee highly noninformative and posterior inferences that are not sensitive to the choice of hyper-parameters. We show the complete theoretical derivation of the full conditional and the variational posterior distributions, and their implementations. We used eight experimental genomic maize and wheat data sets to illustrate the new proposed variational Bayes approximation, and compared its predictions and implementation time with a standard Bayesian genomic model with G×E. Results indicated that prediction accuracies are slightly higher in the standard Bayesian model with G×E than in its variational counterpart, but, in terms of computation time, the variational Bayes genomic model with G×E is, in general, 10 times faster than the conventional Bayesian genomic model with G×E. For this reason, the proposed model may be a useful tool for researchers who need to predict and select genotypes in several environments.

  4. Line scanning, stage scanning confocal microscope (LSSSCM).

    Science.gov (United States)

    Gareau, Daniel S; Krueger, James G; Hawkes, Jason E; Lish, Samantha R; Dietz, Michael P; Mülberger, Alba Guembe; Mu, Euphemia W; Stevenson, Mary L; Lewin, Jesse M; Meehan, Shane A; Carucci, John A

    2017-08-01

    For rapid pathological assessment of large surgical tissue excisions with cellular resolution, we present a line scanning, stage scanning confocal microscope (LSSSCM). LSSSCM uses no scanning mirrors. Laser light is focused with a single cylindrical lens to a line of diffraction-limited width directly into the (Z) sample focal plane, which is parallel to and near the flattened specimen surface. Semi-confocal optical sections are derived from the linear array distribution (Y) and a single mechanical drive that moves the sample parallel to the focal plane and perpendicular to the focused line (X). LSSSCM demonstrates cellular resolution in the conditions of high nuclear density within micronodular basal cell carcinoma.

  5. An overview on Approximate Bayesian computation*

    Directory of Open Access Journals (Sweden)

    Baragatti Meïli

    2014-01-01

    Full Text Available Approximate Bayesian computation techniques, also called likelihood-free methods, are one of the most satisfactory approach to intractable likelihood problems. This overview presents recent results since its introduction about ten years ago in population genetics.

  6. A Bayesian Concept Learning Approach to Crowdsourcing

    DEFF Research Database (Denmark)

    Viappiani, Paolo Renato; Zilles, Sandra; Hamilton, Howard J.

    2011-01-01

    We develop a Bayesian approach to concept learning for crowdsourcing applications. A probabilistic belief over possible concept definitions is maintained and updated according to (noisy) observations from experts, whose behaviors are modeled using discrete types. We propose recommendation...

  7. Bayesian analysis for the social sciences

    CERN Document Server

    Jackman, Simon

    2009-01-01

    Bayesian methods are increasingly being used in the social sciences, as the problems encountered lend themselves so naturally to the subjective qualities of Bayesian methodology. This book provides an accessible introduction to Bayesian methods, tailored specifically for social science students. It contains lots of real examples from political science, psychology, sociology, and economics, exercises in all chapters, and detailed descriptions of all the key concepts, without assuming any background in statistics beyond a first course. It features examples of how to implement the methods using WinBUGS - the most-widely used Bayesian analysis software in the world - and R - an open-source statistical software. The book is supported by a Website featuring WinBUGS and R code, and data sets.

  8. Bayesian Uncertainty Analyses Via Deterministic Model

    Science.gov (United States)

    Krzysztofowicz, R.

    2001-05-01

    Rational decision-making requires that the total uncertainty about a variate of interest (a predictand) be quantified in terms of a probability distribution, conditional on all available information and knowledge. Suppose the state-of-knowledge is embodied in a deterministic model, which is imperfect and outputs only an estimate of the predictand. Fundamentals are presented of three Bayesian approaches to producing a probability distribution of the predictand via any deterministic model. The Bayesian Processor of Output (BPO) quantifies the total uncertainty in terms of a posterior distribution, conditional on model output. The Bayesian Processor of Ensemble (BPE) quantifies the total uncertainty in terms of a posterior distribution, conditional on an ensemble of model output. The Bayesian Forecasting System (BFS) decomposes the total uncertainty into input uncertainty and model uncertainty, which are characterized independently and then integrated into a predictive distribution.

  9. GPstuff: Bayesian Modeling with Gaussian Processes

    NARCIS (Netherlands)

    Vanhatalo, J.; Riihimaki, J.; Hartikainen, J.; Jylänki, P.P.; Tolvanen, V.; Vehtari, A.

    2013-01-01

    The GPstuff toolbox is a versatile collection of Gaussian process models and computational tools required for Bayesian inference. The tools include, among others, various inference methods, sparse approximations and model assessment methods.

  10. Domino effect analysis using Bayesian networks.

    Science.gov (United States)

    Khakzad, Nima; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

    2013-02-01

    A new methodology is introduced based on Bayesian network both to model domino effect propagation patterns and to estimate the domino effect probability at different levels. The flexible structure and the unique modeling techniques offered by Bayesian network make it possible to analyze domino effects through a probabilistic framework, considering synergistic effects, noisy probabilities, and common cause failures. Further, the uncertainties and the complex interactions among the domino effect components are captured using Bayesian network. The probabilities of events are updated in the light of new information, and the most probable path of the domino effect is determined on the basis of the new data gathered. This study shows how probability updating helps to update the domino effect model either qualitatively or quantitatively. The methodology is applied to a hypothetical example and also to an earlier-studied case study. These examples accentuate the effectiveness of Bayesian network in modeling domino effects in processing facility. © 2012 Society for Risk Analysis.

  11. Picturing classical and quantum Bayesian inference

    CERN Document Server

    Coecke, Bob

    2011-01-01

    We introduce a graphical framework for Bayesian inference that is sufficiently general to accommodate not just the standard case but also recent proposals for a theory of quantum Bayesian inference wherein one considers density operators rather than probability distributions as representative of degrees of belief. The diagrammatic framework is stated in the graphical language of symmetric monoidal categories and of compact structures and Frobenius structures therein, in which Bayesian inversion boils down to transposition with respect to an appropriate compact structure. We characterize classical Bayesian inference in terms of a graphical property and demonstrate that our approach eliminates some purely conventional elements that appear in common representations thereof, such as whether degrees of belief are represented by probabilities or entropic quantities. We also introduce a quantum-like calculus wherein the Frobenius structure is noncommutative and show that it can accommodate Leifer's calculus of `cond...

  12. Learning Bayesian networks for discrete data

    KAUST Repository

    Liang, Faming

    2009-02-01

    Bayesian networks have received much attention in the recent literature. In this article, we propose an approach to learn Bayesian networks using the stochastic approximation Monte Carlo (SAMC) algorithm. Our approach has two nice features. Firstly, it possesses the self-adjusting mechanism and thus avoids essentially the local-trap problem suffered by conventional MCMC simulation-based approaches in learning Bayesian networks. Secondly, it falls into the class of dynamic importance sampling algorithms; the network features can be inferred by dynamically weighted averaging the samples generated in the learning process, and the resulting estimates can have much lower variation than the single model-based estimates. The numerical results indicate that our approach can mix much faster over the space of Bayesian networks than the conventional MCMC simulation-based approaches. © 2008 Elsevier B.V. All rights reserved.

  13. An Intuitive Dashboard for Bayesian Network Inference

    Science.gov (United States)

    Reddy, Vikas; Charisse Farr, Anna; Wu, Paul; Mengersen, Kerrie; Yarlagadda, Prasad K. D. V.

    2014-03-01

    Current Bayesian network software packages provide good graphical interface for users who design and develop Bayesian networks for various applications. However, the intended end-users of these networks may not necessarily find such an interface appealing and at times it could be overwhelming, particularly when the number of nodes in the network is large. To circumvent this problem, this paper presents an intuitive dashboard, which provides an additional layer of abstraction, enabling the end-users to easily perform inferences over the Bayesian networks. Unlike most software packages, which display the nodes and arcs of the network, the developed tool organises the nodes based on the cause-and-effect relationship, making the user-interaction more intuitive and friendly. In addition to performing various types of inferences, the users can conveniently use the tool to verify the behaviour of the developed Bayesian network. The tool has been developed using QT and SMILE libraries in C++.

  14. Helical mode lung 4D-CT reconstruction using Bayesian model.

    Science.gov (United States)

    He, Tiancheng; Xue, Zhong; Nitsch, Paige L; Teh, Bin S; Wong, Stephen T

    2013-01-01

    4D computed tomography (CT) has been widely used for treatment planning of thoracic and abdominal cancer radiotherapy. Current 4D-CT lung image reconstruction methods rely on respiratory gating to rearrange the large number of axial images into different phases, which may be subject to external surrogate errors due to poor reproducibility of breathing cycles. New image-matching-based reconstruction works better for the cine mode of 4D-CT acquisition than the helical mode because the table position of each axial image is different in helical mode and image matching might suffer from bigger errors. In helical mode, not only the phases but also the un-uniform table positions of images need to be considered. We propose a Bayesian method for automated 4D-CT lung image reconstruction in helical mode 4D scans. Each axial image is assigned to a respiratory phase based on the Bayesian framework that ensures spatial and temporal smoothness of surfaces of anatomical structures. Iterative optimization is used to reconstruct a series of 3D-CT images for subjects undergoing 4D scans. In experiments, we compared visually and quantitatively the results of the proposed Bayesian 4D-CT reconstruction algorithm with the respiratory surrogate and the image matching-based method. The results showed that the proposed algorithm yielded better 4D-CT for helical scans.

  15. A Bayesian spatial approach for predicting seagrass occurrence

    Science.gov (United States)

    March, D.; Alós, J.; Cabanellas-Reboredo, M.; Infantes, E.; Jordi, A.; Palmer, M.

    2013-10-01

    We implement a Bayesian spatial approach to predict and map the probability of occurrence of seagrass Posidonia oceanica at high spatial resolution based environmental variables. We found that depth, near-bottom orbital velocities and a spectral pattern of Landsat imagery were relevant environmental variables, although there was no effect of slope or water residence time. We generated a data inventory of P. oceanica samples at Palma Bay, NW Mediterranean, from three main sources: side scan sonar, aerial imagery and a customized drop-camera system. A hierarchical Bayesian spatial model for non-Gaussian data was used to relate presence-absence data of P. oceanica with environmental variables in the presence of spatial autocorrelation (SA). A spatial dimension reduction method, the predictive process approach, was implemented to overcome computational constraints for moderately large datasets. Our results suggest that incorporating spatial random effects removes SA from the residuals and improves model fit compared to non-spatial regression models. The main products of this work were probability and uncertainty model maps, which could benefit seagrass management and the assessment of the ecological status of seagrass meadows.

  16. Variational Bayesian Approximation methods for inverse problems

    Science.gov (United States)

    Mohammad-Djafari, Ali

    2012-09-01

    Variational Bayesian Approximation (VBA) methods are recent tools for effective Bayesian computations. In this paper, these tools are used for inverse problems where the prior models include hidden variables and where where the estimation of the hyper parameters has also to be addressed. In particular two specific prior models (Student-t and mixture of Gaussian models) are considered and details of the algorithms are given.

  17. Bayesian Modeling of a Human MMORPG Player

    CERN Document Server

    Synnaeve, Gabriel

    2010-01-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  18. Bayesian Modeling of a Human MMORPG Player

    Science.gov (United States)

    Synnaeve, Gabriel; Bessière, Pierre

    2011-03-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  19. Fuzzy Functional Dependencies and Bayesian Networks

    Institute of Scientific and Technical Information of China (English)

    LIU WeiYi(刘惟一); SONG Ning(宋宁)

    2003-01-01

    Bayesian networks have become a popular technique for representing and reasoning with probabilistic information. The fuzzy functional dependency is an important kind of data dependencies in relational databases with fuzzy values. The purpose of this paper is to set up a connection between these data dependencies and Bayesian networks. The connection is done through a set of methods that enable people to obtain the most information of independent conditions from fuzzy functional dependencies.

  20. A Bayesian classifier for symbol recognition

    OpenAIRE

    Barrat, Sabine; Tabbone, Salvatore; Nourrissier, Patrick

    2007-01-01

    URL : http://www.buyans.com/POL/UploadedFile/134_9977.pdf; International audience; We present in this paper an original adaptation of Bayesian networks to symbol recognition problem. More precisely, a descriptor combination method, which enables to improve significantly the recognition rate compared to the recognition rates obtained by each descriptor, is presented. In this perspective, we use a simple Bayesian classifier, called naive Bayes. In fact, probabilistic graphical models, more spec...

  1. Bayesian Inversion of Seabed Scattering Data

    Science.gov (United States)

    2014-09-30

    uncertainties as well as parameter values, thereby quantifying the information content of the data to resolve the model parameters. Bayesian inversion...method based on deviance information criterion to determine the dominant scattering mechanism is in development. This work has been compiled in two... Bayesian Inversion of Seabed Scattering Data (Special Research Award in Ocean Acoustics) Gavin A.M.W. Steininger School of Earth & Ocean

  2. Bayesian target tracking based on particle filter

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    For being able to deal with the nonlinear or non-Gaussian problems, particle filters have been studied by many researchers. Based on particle filter, the extended Kalman filter (EKF) proposal function is applied to Bayesian target tracking. Markov chain Monte Carlo (MCMC) method, the resampling step, etc novel techniques are also introduced into Bayesian target tracking. And the simulation results confirm the improved particle filter with these techniques outperforms the basic one.

  3. ProFit: Bayesian galaxy fitting tool

    Science.gov (United States)

    Robotham, A. S. G.; Taranu, D.; Tobar, R.

    2016-12-01

    ProFit is a Bayesian galaxy fitting tool that uses the fast C++ image generation library libprofit (ascl:1612.003) and a flexible R interface to a large number of likelihood samplers. It offers a fully featured Bayesian interface to galaxy model fitting (also called profiling), using mostly the same standard inputs as other popular codes (e.g. GALFIT ascl:1104.010), but it is also able to use complex priors and a number of likelihoods.

  4. BNFinder2: Faster Bayesian network learning and Bayesian classification.

    Science.gov (United States)

    Dojer, Norbert; Bednarz, Pawel; Podsiadlo, Agnieszka; Wilczynski, Bartek

    2013-08-15

    Bayesian Networks (BNs) are versatile probabilistic models applicable to many different biological phenomena. In biological applications the structure of the network is usually unknown and needs to be inferred from experimental data. BNFinder is a fast software implementation of an exact algorithm for finding the optimal structure of the network given a number of experimental observations. Its second version, presented in this article, represents a major improvement over the previous version. The improvements include (i) a parallelized learning algorithm leading to an order of magnitude speed-ups in BN structure learning time; (ii) inclusion of an additional scoring function based on mutual information criteria; (iii) possibility of choosing the resulting network specificity based on statistical criteria and (iv) a new module for classification by BNs, including cross-validation scheme and classifier quality measurements with receiver operator characteristic scores. BNFinder2 is implemented in python and freely available under the GNU general public license at the project Web site https://launchpad.net/bnfinder, together with a user's manual, introductory tutorial and supplementary methods.

  5. Philosophy and the practice of Bayesian statistics.

    Science.gov (United States)

    Gelman, Andrew; Shalizi, Cosma Rohilla

    2013-02-01

    A substantial school in the philosophy of science identifies Bayesian inference with inductive inference and even rationality as such, and seems to be strengthened by the rise and practical success of Bayesian statistics. We argue that the most successful forms of Bayesian statistics do not actually support that particular philosophy but rather accord much better with sophisticated forms of hypothetico-deductivism. We examine the actual role played by prior distributions in Bayesian models, and the crucial aspects of model checking and model revision, which fall outside the scope of Bayesian confirmation theory. We draw on the literature on the consistency of Bayesian updating and also on our experience of applied work in social science. Clarity about these matters should benefit not just philosophy of science, but also statistical practice. At best, the inductivist view has encouraged researchers to fit and compare models without checking them; at worst, theorists have actively discouraged practitioners from performing model checking because it does not fit into their framework.

  6. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... interfere with the procedure. You will receive specific instructions based on the type of scan you are ... after your nuclear medicine scan. If any special instructions are necessary, you will be informed by a ...

  7. RBC nuclear scan

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  9. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  10. Bayesian inference on the sphere beyond statistical isotropy

    CERN Document Server

    Das, Santanu; Souradeep, Tarun

    2015-01-01

    We present a general method for Bayesian inference of the underlying covariance structure of random fields on a sphere. We employ the Bipolar Spherical Harmonic (BipoSH) representation of general covariance structure on the sphere. We illustrate the efficacy of the method as a principled approach to assess violation of statistical isotropy (SI) in the sky maps of Cosmic Microwave Background (CMB) fluctuations. SI violation in observed CMB maps arise due to known physical effects such as Doppler boost and weak lensing; yet unknown theoretical possibilities like cosmic topology and subtle violations of the cosmological principle, as well as, expected observational artefacts of scanning the sky with a non-circular beam, masking, foreground residuals, anisotropic noise, etc. We explicitly demonstrate the recovery of the input SI violation signals with their full statistics in simulated CMB maps. Our formalism easily adapts to exploring parametric physical models with non-SI covariance, as we illustrate for the in...

  11. Pulmonary ventilation/perfusion scan

    Science.gov (United States)

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health care provider injects ...

  12. Cloud clearing techniques over land for land surface temperature retrieval from the Advanced Along Track Scanning Radiometer

    OpenAIRE

    Bulgin, C.E.; H. Sembhi; D. Ghent; Remedios, J.J.; Merchant, Christopher

    2014-01-01

    We present five new cloud detection algorithms over land based on dynamic threshold or Bayesian techniques, applicable to the Advanced Along Track Scanning Radiometer (AATSR) instrument and compare these with the standard threshold based SADIST cloud detection scheme. We use a manually classified dataset as a reference to assess algorithm performance and quantify the impact of each cloud detection scheme on land surface temperature (LST) retrieval. The use of probabilistic Bayesian cloud dete...

  13. Bayesian inference for OPC modeling

    Science.gov (United States)

    Burbine, Andrew; Sturtevant, John; Fryer, David; Smith, Bruce W.

    2016-03-01

    The use of optical proximity correction (OPC) demands increasingly accurate models of the photolithographic process. Model building and inference techniques in the data science community have seen great strides in the past two decades which make better use of available information. This paper aims to demonstrate the predictive power of Bayesian inference as a method for parameter selection in lithographic models by quantifying the uncertainty associated with model inputs and wafer data. Specifically, the method combines the model builder's prior information about each modelling assumption with the maximization of each observation's likelihood as a Student's t-distributed random variable. Through the use of a Markov chain Monte Carlo (MCMC) algorithm, a model's parameter space is explored to find the most credible parameter values. During parameter exploration, the parameters' posterior distributions are generated by applying Bayes' rule, using a likelihood function and the a priori knowledge supplied. The MCMC algorithm used, an affine invariant ensemble sampler (AIES), is implemented by initializing many walkers which semiindependently explore the space. The convergence of these walkers to global maxima of the likelihood volume determine the parameter values' highest density intervals (HDI) to reveal champion models. We show that this method of parameter selection provides insights into the data that traditional methods do not and outline continued experiments to vet the method.

  14. Bayesian analysis of cosmic structures

    CERN Document Server

    Kitaura, Francisco-Shu

    2011-01-01

    We revise the Bayesian inference steps required to analyse the cosmological large-scale structure. Here we make special emphasis in the complications which arise due to the non-Gaussian character of the galaxy and matter distribution. In particular we investigate the advantages and limitations of the Poisson-lognormal model and discuss how to extend this work. With the lognormal prior using the Hamiltonian sampling technique and on scales of about 4 h^{-1} Mpc we find that the over-dense regions are excellent reconstructed, however, under-dense regions (void statistics) are quantitatively poorly recovered. Contrary to the maximum a posteriori (MAP) solution which was shown to over-estimate the density in the under-dense regions we obtain lower densities than in N-body simulations. This is due to the fact that the MAP solution is conservative whereas the full posterior yields samples which are consistent with the prior statistics. The lognormal prior is not able to capture the full non-linear regime at scales ...

  15. Bayesian demography 250 years after Bayes.

    Science.gov (United States)

    Bijak, Jakub; Bryant, John

    2016-01-01

    Bayesian statistics offers an alternative to classical (frequentist) statistics. It is distinguished by its use of probability distributions to describe uncertain quantities, which leads to elegant solutions to many difficult statistical problems. Although Bayesian demography, like Bayesian statistics more generally, is around 250 years old, only recently has it begun to flourish. The aim of this paper is to review the achievements of Bayesian demography, address some misconceptions, and make the case for wider use of Bayesian methods in population studies. We focus on three applications: demographic forecasts, limited data, and highly structured or complex models. The key advantages of Bayesian methods are the ability to integrate information from multiple sources and to describe uncertainty coherently. Bayesian methods also allow for including additional (prior) information next to the data sample. As such, Bayesian approaches are complementary to many traditional methods, which can be productively re-expressed in Bayesian terms.

  16. Bayesian analysis of censored response data in family-based genetic association studies.

    Science.gov (United States)

    Del Greco M, Fabiola; Pattaro, Cristian; Minelli, Cosetta; Thompson, John R

    2016-09-01

    Biomarkers are subject to censoring whenever some measurements are not quantifiable given a laboratory detection limit. Methods for handling censoring have received less attention in genetic epidemiology, and censored data are still often replaced with a fixed value. We compared different strategies for handling a left-censored continuous biomarker in a family-based study, where the biomarker is tested for association with a genetic variant, S, adjusting for a covariate, X. Allowing different correlations between X and S, we compared simple substitution of censored observations with the detection limit followed by a linear mixed effect model (LMM), Bayesian model with noninformative priors, Tobit model with robust standard errors, the multiple imputation (MI) with and without S in the imputation followed by a LMM. Our comparison was based on real and simulated data in which 20% and 40% censoring were artificially induced. The complete data were also analyzed with a LMM. In the MICROS study, the Bayesian model gave results closer to those obtained with the complete data. In the simulations, simple substitution was always the most biased method, the Tobit approach gave the least biased estimates at all censoring levels and correlation values, the Bayesian model and both MI approaches gave slightly biased estimates but smaller root mean square errors. On the basis of these results the Bayesian approach is highly recommended for candidate gene studies; however, the computationally simpler Tobit and the MI without S are both good options for genome-wide studies.

  17. An introduction to Gaussian Bayesian networks.

    Science.gov (United States)

    Grzegorczyk, Marco

    2010-01-01

    The extraction of regulatory networks and pathways from postgenomic data is important for drug -discovery and development, as the extracted pathways reveal how genes or proteins regulate each other. Following up on the seminal paper of Friedman et al. (J Comput Biol 7:601-620, 2000), Bayesian networks have been widely applied as a popular tool to this end in systems biology research. Their popularity stems from the tractability of the marginal likelihood of the network structure, which is a consistent scoring scheme in the Bayesian context. This score is based on an integration over the entire parameter space, for which highly expensive computational procedures have to be applied when using more complex -models based on differential equations; for example, see (Bioinformatics 24:833-839, 2008). This chapter gives an introduction to reverse engineering regulatory networks and pathways with Gaussian Bayesian networks, that is Bayesian networks with the probabilistic BGe scoring metric [see (Geiger and Heckerman 235-243, 1995)]. In the BGe model, the data are assumed to stem from a Gaussian distribution and a normal-Wishart prior is assigned to the unknown parameters. Gaussian Bayesian network methodology for analysing static observational, static interventional as well as dynamic (observational) time series data will be described in detail in this chapter. Finally, we apply these Bayesian network inference methods (1) to observational and interventional flow cytometry (protein) data from the well-known RAF pathway to evaluate the global network reconstruction accuracy of Bayesian network inference and (2) to dynamic gene expression time series data of nine circadian genes in Arabidopsis thaliana to reverse engineer the unknown regulatory network topology for this domain.

  18. Bayesian prediction of microbial oxygen requirement [v1; ref status: indexed, http://f1000r.es/1m6

    Directory of Open Access Journals (Sweden)

    Dan B. Jensen

    2013-09-01

    Full Text Available Background: Prediction of the optimal habitat conditions for a given bacterium, based on genome sequence alone would be of value for scientific as well as industrial purposes. One example of such a habitat adaptation is the requirement for oxygen. In spite of good genome data availability, there have been only a few prediction attempts of bacterial oxygen requirements, using genome sequences. Here, we describe a method for distinguishing aerobic, anaerobic and facultative anaerobic bacteria, based on genome sequence-derived input, using naive Bayesian inference. In contrast, other studies found in literature only demonstrate the ability to distinguish two classes at a time. Results: The results shown in the present study are as good as or better than comparable methods previously described in the scientific literature, with an arguably simpler method, when results are directly compared. This method further compares the performance of a single-step naive Bayesian prediction of the three included classifications, compared to a simple Bayesian network with two steps. A two-step network, distinguishing first respiring from non-respiring organisms, followed by the distinction of aerobe and facultative anaerobe organisms within the respiring group, is found to perform best. Conclusions: A simple naive Bayesian network based on the presence or absence of specific protein domains within a genome is an effective and easy way to predict bacterial habitat preferences, such as oxygen requirement.

  19. Radiation dose reduction in computed tomography perfusion using spatial-temporal Bayesian methods

    Science.gov (United States)

    Fang, Ruogu; Raj, Ashish; Chen, Tsuhan; Sanelli, Pina C.

    2012-03-01

    In current computed tomography (CT) examinations, the associated X-ray radiation dose is of significant concern to patients and operators, especially CT perfusion (CTP) imaging that has higher radiation dose due to its cine scanning technique. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) parameter as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and degrade CT perfusion maps greatly if no adequate noise control is applied during image reconstruction. To capture the essential dynamics of CT perfusion, a simple spatial-temporal Bayesian method that uses a piecewise parametric model of the residual function is used, and then the model parameters are estimated from a Bayesian formulation of prior smoothness constraints on perfusion parameters. From the fitted residual function, reliable CTP parameter maps are obtained from low dose CT data. The merit of this scheme exists in the combination of analytical piecewise residual function with Bayesian framework using a simpler prior spatial constrain for CT perfusion application. On a dataset of 22 patients, this dynamic spatial-temporal Bayesian model yielded an increase in signal-tonoise-ratio (SNR) of 78% and a decrease in mean-square-error (MSE) of 40% at low dose radiation of 43mA.

  20. Bayesian Calibration of Microsimulation Models.

    Science.gov (United States)

    Rutter, Carolyn M; Miglioretti, Diana L; Savarino, James E

    2009-12-01

    Microsimulation models that describe disease processes synthesize information from multiple sources and can be used to estimate the effects of screening and treatment on cancer incidence and mortality at a population level. These models are characterized by simulation of individual event histories for an idealized population of interest. Microsimulation models are complex and invariably include parameters that are not well informed by existing data. Therefore, a key component of model development is the choice of parameter values. Microsimulation model parameter values are selected to reproduce expected or known results though the process of model calibration. Calibration may be done by perturbing model parameters one at a time or by using a search algorithm. As an alternative, we propose a Bayesian method to calibrate microsimulation models that uses Markov chain Monte Carlo. We show that this approach converges to the target distribution and use a simulation study to demonstrate its finite-sample performance. Although computationally intensive, this approach has several advantages over previously proposed methods, including the use of statistical criteria to select parameter values, simultaneous calibration of multiple parameters to multiple data sources, incorporation of information via prior distributions, description of parameter identifiability, and the ability to obtain interval estimates of model parameters. We develop a microsimulation model for colorectal cancer and use our proposed method to calibrate model parameters. The microsimulation model provides a good fit to the calibration data. We find evidence that some parameters are identified primarily through prior distributions. Our results underscore the need to incorporate multiple sources of variability (i.e., due to calibration data, unknown parameters, and estimated parameters and predicted values) when calibrating and applying microsimulation models.