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Sample records for nonparametric linkage analysis

  1. Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, J H; Iachine, I

    2004-01-01

    This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently...... developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated...... in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity....

  2. A Unified Discussion on the Concept of Score Functions Used in the Context of Nonparametric Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Lars Ängquist

    2008-01-01

    Full Text Available In this article we try to discuss nonparametric linkage (NPL score functions within a broad and quite general framework. The main focus of the paper is the structure, derivation principles and interpretations of the score function entity itself. We define and discuss several families of one-locus score function definitions, i.e. the implicit, explicit and optimal ones. Some generalizations and comments to the two-locus, unconditional and conditional, cases are included as well. Although this article mainly aims at serving as an overview, where the concept of score functions are put into a covering context, we generalize the noncentrality parameter (NCP optimal score functions in Ängquist et al. (2007 to facilitate—through weighting—for incorporation of several plausible distinct genetic models. Since the genetic model itself most oftenly is to some extent unknown this facilitates weaker prior assumptions with respect to plausible true disease models without loosing the property of NCP-optimality. Moreover, we discuss general assumptions and properties of score functions in the above sense. For instance, the concept of identical by descent (IBD sharing structures and score function equivalence are discussed in some detail.

  3. 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.

  4. A Bayesian nonparametric meta-analysis model.

    Science.gov (United States)

    Karabatsos, George; Talbott, Elizabeth; Walker, Stephen G

    2015-03-01

    In a meta-analysis, it is important to specify a model that adequately describes the effect-size distribution of the underlying population of studies. The conventional normal fixed-effect and normal random-effects models assume a normal effect-size population distribution, conditionally on parameters and covariates. For estimating the mean overall effect size, such models may be adequate, but for prediction, they surely are not if the effect-size distribution exhibits non-normal behavior. To address this issue, we propose a Bayesian nonparametric meta-analysis model, which can describe a wider range of effect-size distributions, including unimodal symmetric distributions, as well as skewed and more multimodal distributions. We demonstrate our model through the analysis of real meta-analytic data arising from behavioral-genetic research. We compare the predictive performance of the Bayesian nonparametric model against various conventional and more modern normal fixed-effects and random-effects models.

  5. Nonparametric Bayes analysis of social science data

    Science.gov (United States)

    Kunihama, Tsuyoshi

    Social science data often contain complex characteristics that standard statistical methods fail to capture. Social surveys assign many questions to respondents, which often consist of mixed-scale variables. Each of the variables can follow a complex distribution outside parametric families and associations among variables may have more complicated structures than standard linear dependence. Therefore, it is not straightforward to develop a statistical model which can approximate structures well in the social science data. In addition, many social surveys have collected data over time and therefore we need to incorporate dynamic dependence into the models. Also, it is standard to observe massive number of missing values in the social science data. To address these challenging problems, this thesis develops flexible nonparametric Bayesian methods for the analysis of social science data. Chapter 1 briefly explains backgrounds and motivations of the projects in the following chapters. Chapter 2 develops a nonparametric Bayesian modeling of temporal dependence in large sparse contingency tables, relying on a probabilistic factorization of the joint pmf. Chapter 3 proposes nonparametric Bayes inference on conditional independence with conditional mutual information used as a measure of the strength of conditional dependence. Chapter 4 proposes a novel Bayesian density estimation method in social surveys with complex designs where there is a gap between sample and population. We correct for the bias by adjusting mixture weights in Bayesian mixture models. Chapter 5 develops a nonparametric model for mixed-scale longitudinal surveys, in which various types of variables can be induced through latent continuous variables and dynamic latent factors lead to flexibly time-varying associations among variables.

  6. Local Component Analysis for Nonparametric Bayes Classifier

    CERN Document Server

    Khademi, Mahmoud; safayani, Meharn

    2010-01-01

    The decision boundaries of Bayes classifier are optimal because they lead to maximum probability of correct decision. It means if we knew the prior probabilities and the class-conditional densities, we could design a classifier which gives the lowest probability of error. However, in classification based on nonparametric density estimation methods such as Parzen windows, the decision regions depend on the choice of parameters such as window width. Moreover, these methods suffer from curse of dimensionality of the feature space and small sample size problem which severely restricts their practical applications. In this paper, we address these problems by introducing a novel dimension reduction and classification method based on local component analysis. In this method, by adopting an iterative cross-validation algorithm, we simultaneously estimate the optimal transformation matrices (for dimension reduction) and classifier parameters based on local information. The proposed method can classify the data with co...

  7. Linkage analysis in alcohol dependence.

    Science.gov (United States)

    Windemuth, C; Hahn, A; Strauch, K; Baur, M P; Wienker, T F

    1999-01-01

    Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucasian ancestry comprising 745 persons, 339 of whom are affected according to DSM-III-R and Feighner criteria. Using parametric and nonparametric methods, evidence for linkage was found on chromosome 1 (near markers D1S532, D1S1588, and D1S534), as well as on chromosome 15 (near marker D15S642). Other regions of the genome showed suggestive evidence for contributing loci. Related findings are discussed in recent publications investigating linkage in humans [Reich et al., 1998] and mice [Melo et al., 1996].

  8. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been ...

  9. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been...

  10. A Nonparametric Analogy of Analysis of Covariance

    Science.gov (United States)

    Burnett, Thomas D.; Barr, Donald R.

    1977-01-01

    A nonparametric test of the hypothesis of no treatment effect is suggested for a situation where measures of the severity of the condition treated can be obtained and ranked both pre- and post-treatment. The test allows the pre-treatment rank to be used as a concomitant variable. (Author/JKS)

  11. Model-free linkage analysis of a binary trait.

    Science.gov (United States)

    Xu, Wei; Bull, Shelley B; Mirea, Lucia; Greenwood, Celia M T

    2012-01-01

    Genetic linkage analysis aims to detect chromosomal regions containing genes that influence risk of specific inherited diseases. The presence of linkage is indicated when a disease or trait cosegregates through the families with genetic markers at a particular region of the genome. Two main types of genetic linkage analysis are in common use, namely model-based linkage analysis and model-free linkage analysis. In this chapter, we focus solely on the latter type and specifically on binary traits or phenotypes, such as the presence or absence of a specific disease. Model-free linkage analysis is based on allele-sharing, where patterns of genetic similarity among affected relatives are compared to chance expectations. Because the model-free methods do not require the specification of the inheritance parameters of a genetic model, they are preferred by many researchers at early stages in the study of a complex disease. We introduce the history of model-free linkage analysis in Subheading 1. Table 1 describes a standard model-free linkage analysis workflow. We describe three popular model-free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees. The theory behind each linkage test is described in this section, together with a simple example of the relevant calculations. Table 4 provides a summary of popular genetic analysis software packages that implement model-free linkage models. In Subheading 2, we work through the methods on a rich example providing sample software code and output. Subheading 3 contains notes with additional details on various topics that may need further consideration during analysis.

  12. Lottery spending: a non-parametric analysis.

    Science.gov (United States)

    Garibaldi, Skip; Frisoli, Kayla; Ke, Li; Lim, Melody

    2015-01-01

    We analyze the spending of individuals in the United States on lottery tickets in an average month, as reported in surveys. We view these surveys as sampling from an unknown distribution, and we use non-parametric methods to compare properties of this distribution for various demographic groups, as well as claims that some properties of this distribution are constant across surveys. We find that the observed higher spending by Hispanic lottery players can be attributed to differences in education levels, and we dispute previous claims that the top 10% of lottery players consistently account for 50% of lottery sales.

  13. Lottery spending: a non-parametric analysis.

    Directory of Open Access Journals (Sweden)

    Skip Garibaldi

    Full Text Available We analyze the spending of individuals in the United States on lottery tickets in an average month, as reported in surveys. We view these surveys as sampling from an unknown distribution, and we use non-parametric methods to compare properties of this distribution for various demographic groups, as well as claims that some properties of this distribution are constant across surveys. We find that the observed higher spending by Hispanic lottery players can be attributed to differences in education levels, and we dispute previous claims that the top 10% of lottery players consistently account for 50% of lottery sales.

  14. Investigating the cultural patterns of corruption: A nonparametric analysis

    OpenAIRE

    Halkos, George; Tzeremes, Nickolaos

    2011-01-01

    By using a sample of 77 countries our analysis applies several nonparametric techniques in order to reveal the link between national culture and corruption. Based on Hofstede’s cultural dimensions and the corruption perception index, the results reveal that countries with higher levels of corruption tend to have higher power distance and collectivism values in their society.

  15. Parametric and nonparametric Granger causality testing: Linkages between international stock markets

    NARCIS (Netherlands)

    de Gooijer, J.G.; Sivarajasingham, S.

    2008-01-01

    This study investigates long-term linear and nonlinear causal linkages among eleven stock markets, six industrialized markets and five emerging markets of South-East Asia. We cover the period 1987-2006, taking into account the on-set of the Asian financial crisis of 1997. We first apply a test for t

  16. A Bayesian Nonparametric Meta-Analysis Model

    Science.gov (United States)

    Karabatsos, George; Talbott, Elizabeth; Walker, Stephen G.

    2015-01-01

    In a meta-analysis, it is important to specify a model that adequately describes the effect-size distribution of the underlying population of studies. The conventional normal fixed-effect and normal random-effects models assume a normal effect-size population distribution, conditionally on parameters and covariates. For estimating the mean overall…

  17. Nonparametric inference procedures for multistate life table analysis.

    Science.gov (United States)

    Dow, M M

    1985-01-01

    Recent generalizations of the classical single state life table procedures to the multistate case provide the means to analyze simultaneously the mobility and mortality experience of 1 or more cohorts. This paper examines fairly general nonparametric combinatorial matrix procedures, known as quadratic assignment, as an analysis technic of various transitional patterns commonly generated by cohorts over the life cycle course. To some degree, the output from a multistate life table analysis suggests inference procedures. In his discussion of multstate life table construction features, the author focuses on the matrix formulation of the problem. He then presents several examples of the proposed nonparametric procedures. Data for the mobility and life expectancies at birth matrices come from the 458 member Cayo Santiago rhesus monkey colony. The author's matrix combinatorial approach to hypotheses testing may prove to be a useful inferential strategy in several multidimensional demographic areas.

  18. Using non-parametric methods in econometric production analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    2012-01-01

    by investigating the relationship between the elasticity of scale and the farm size. We use a balanced panel data set of 371~specialised crop farms for the years 2004-2007. A non-parametric specification test shows that neither the Cobb-Douglas function nor the Translog function are consistent with the "true......Econometric estimation of production functions is one of the most common methods in applied economic production analysis. These studies usually apply parametric estimation techniques, which obligate the researcher to specify a functional form of the production function of which the Cobb...... parameter estimates, but also in biased measures which are derived from the parameters, such as elasticities. Therefore, we propose to use non-parametric econometric methods. First, these can be applied to verify the functional form used in parametric production analysis. Second, they can be directly used...

  19. Using non-parametric methods in econometric production analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    -Douglas function nor the Translog function are consistent with the “true” relationship between the inputs and the output in our data set. We solve this problem by using non-parametric regression. This approach delivers reasonable results, which are on average not too different from the results of the parametric......Econometric estimation of production functions is one of the most common methods in applied economic production analysis. These studies usually apply parametric estimation techniques, which obligate the researcher to specify the functional form of the production function. Most often, the Cobb...... results—including measures that are of interest of applied economists, such as elasticities. Therefore, we propose to use nonparametric econometric methods. First, they can be applied to verify the functional form used in parametric estimations of production functions. Second, they can be directly used...

  20. Digital spectral analysis parametric, non-parametric and advanced methods

    CERN Document Server

    Castanié, Francis

    2013-01-01

    Digital Spectral Analysis provides a single source that offers complete coverage of the spectral analysis domain. This self-contained work includes details on advanced topics that are usually presented in scattered sources throughout the literature.The theoretical principles necessary for the understanding of spectral analysis are discussed in the first four chapters: fundamentals, digital signal processing, estimation in spectral analysis, and time-series models.An entire chapter is devoted to the non-parametric methods most widely used in industry.High resolution methods a

  1. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  2. Linkage and association analysis of CACNG3 in childhood absence epilepsy

    DEFF Research Database (Denmark)

    Everett, Kate V; Chioza, Barry; Aicardi, Jean

    2007-01-01

    and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD = 3.54, alpha = 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P ... and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P

  3. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    2007-01-01

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  4. Using non-parametric methods in econometric production analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    2012-01-01

    Econometric estimation of production functions is one of the most common methods in applied economic production analysis. These studies usually apply parametric estimation techniques, which obligate the researcher to specify a functional form of the production function of which the Cobb-Douglas a......Econometric estimation of production functions is one of the most common methods in applied economic production analysis. These studies usually apply parametric estimation techniques, which obligate the researcher to specify a functional form of the production function of which the Cobb...... parameter estimates, but also in biased measures which are derived from the parameters, such as elasticities. Therefore, we propose to use non-parametric econometric methods. First, these can be applied to verify the functional form used in parametric production analysis. Second, they can be directly used...... to estimate production functions without the specification of a functional form. Therefore, they avoid possible misspecification errors due to the use of an unsuitable functional form. In this paper, we use parametric and non-parametric methods to identify the optimal size of Polish crop farms...

  5. Glaucoma Monitoring in a Clinical Setting Glaucoma Progression Analysis vs Nonparametric Progression Analysis in the Groningen Longitudinal Glaucoma Study

    NARCIS (Netherlands)

    Wesselink, Christiaan; Heeg, Govert P.; Jansonius, Nomdo M.

    Objective: To compare prospectively 2 perimetric progression detection algorithms for glaucoma, the Early Manifest Glaucoma Trial algorithm (glaucoma progression analysis [GPA]) and a nonparametric algorithm applied to the mean deviation (MD) (nonparametric progression analysis [NPA]). Methods:

  6. Linkage analysis of chromosome 14 and essential hypertension in Chinese population

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-yan; HUANG Jian-feng; GE Dong-liang; SU Shao-yong; LI Biao; GU Dong-feng

    2005-01-01

    Background Hypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings. Methods A linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package. Results In the qualitative analysis, the highest non-parametric linkage score is 1.0 (P=0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with λs≥2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure. Conclusion There was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.

  7. Using non-parametric methods in econometric production analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    Econometric estimation of production functions is one of the most common methods in applied economic production analysis. These studies usually apply parametric estimation techniques, which obligate the researcher to specify the functional form of the production function. Most often, the Cobb......-Douglas or the Translog production function is used. However, the specification of a functional form for the production function involves the risk of specifying a functional form that is not similar to the “true” relationship between the inputs and the output. This misspecification might result in biased estimation...... results—including measures that are of interest of applied economists, such as elasticities. Therefore, we propose to use nonparametric econometric methods. First, they can be applied to verify the functional form used in parametric estimations of production functions. Second, they can be directly used...

  8. Multi-Directional Non-Parametric Analysis of Agricultural Efficiency

    DEFF Research Database (Denmark)

    Balezentis, Tomas

    This thesis seeks to develop methodologies for assessment of agricultural efficiency and employ them to Lithuanian family farms. In particular, we focus on three particular objectives throughout the research: (i) to perform a fully non-parametric analysis of efficiency effects, (ii) to extend...... relative to labour, intermediate consumption and land (in some cases land was not treated as a discretionary input). These findings call for further research on relationships among financial structure, investment decisions, and efficiency in Lithuanian family farms. Application of different techniques...... of stochasticity associated with Lithuanian family farm performance. The former technique showed that the farms differed in terms of the mean values and variance of the efficiency scores over time with some clear patterns prevailing throughout the whole research period. The fuzzy Free Disposal Hull showed...

  9. Bayesian nonparametric meta-analysis using Polya tree mixture models.

    Science.gov (United States)

    Branscum, Adam J; Hanson, Timothy E

    2008-09-01

    Summary. A common goal in meta-analysis is estimation of a single effect measure using data from several studies that are each designed to address the same scientific inquiry. Because studies are typically conducted in geographically disperse locations, recent developments in the statistical analysis of meta-analytic data involve the use of random effects models that account for study-to-study variability attributable to differences in environments, demographics, genetics, and other sources that lead to heterogeneity in populations. Stemming from asymptotic theory, study-specific summary statistics are modeled according to normal distributions with means representing latent true effect measures. A parametric approach subsequently models these latent measures using a normal distribution, which is strictly a convenient modeling assumption absent of theoretical justification. To eliminate the influence of overly restrictive parametric models on inferences, we consider a broader class of random effects distributions. We develop a novel hierarchical Bayesian nonparametric Polya tree mixture (PTM) model. We present methodology for testing the PTM versus a normal random effects model. These methods provide researchers a straightforward approach for conducting a sensitivity analysis of the normality assumption for random effects. An application involving meta-analysis of epidemiologic studies designed to characterize the association between alcohol consumption and breast cancer is presented, which together with results from simulated data highlight the performance of PTMs in the presence of nonnormality of effect measures in the source population.

  10. Nonparametric Cointegration Analysis of Fractional Systems With Unknown Integration Orders

    DEFF Research Database (Denmark)

    Nielsen, Morten Ørregaard

    2009-01-01

    In this paper a nonparametric variance ratio testing approach is proposed for determining the number of cointegrating relations in fractionally integrated systems. The test statistic is easily calculated without prior knowledge of the integration order of the data, the strength of the cointegrating...

  11. Non-parametric analysis of rating transition and default data

    DEFF Research Database (Denmark)

    Fledelius, Peter; Lando, David; Perch Nielsen, Jens

    2004-01-01

    We demonstrate the use of non-parametric intensity estimation - including construction of pointwise confidence sets - for analyzing rating transition data. We find that transition intensities away from the class studied here for illustration strongly depend on the direction of the previous move b...... but that this dependence vanishes after 2-3 years....

  12. Non-parametric analysis of rating transition and default data

    DEFF Research Database (Denmark)

    Fledelius, Peter; Lando, David; Perch Nielsen, Jens

    2004-01-01

    We demonstrate the use of non-parametric intensity estimation - including construction of pointwise confidence sets - for analyzing rating transition data. We find that transition intensities away from the class studied here for illustration strongly depend on the direction of the previous move...

  13. Poverty and life cycle effects: A nonparametric analysis for Germany

    OpenAIRE

    Stich, Andreas

    1996-01-01

    Most empirical studies on poverty consider the extent of poverty either for the entire society or for separate groups like elderly people.However, these papers do not show what the situation looks like for persons of a certain age. In this paper poverty measures depending on age are derived using the joint density of income and age. The density is nonparametrically estimated by weighted Gaussian kernel density estimation. Applying the conditional density of income to several poverty measures ...

  14. ANALYSIS OF TIED DATA: AN ALTERNATIVE NON-PARAMETRIC APPROACH

    Directory of Open Access Journals (Sweden)

    I. C. A. OYEKA

    2012-02-01

    Full Text Available This paper presents a non-parametric statistical method of analyzing two-sample data that makes provision for the possibility of ties in the data. A test statistic is developed and shown to be free of the effect of any possible ties in the data. An illustrative example is provided and the method is shown to compare favourably with its competitor; the Mann-Whitney test and is more powerful than the latter when there are ties.

  15. A Bayesian nonparametric method for prediction in EST analysis

    Directory of Open Access Journals (Sweden)

    Prünster Igor

    2007-09-01

    Full Text Available Abstract Background Expressed sequence tags (ESTs analyses are a fundamental tool for gene identification in organisms. Given a preliminary EST sample from a certain library, several statistical prediction problems arise. In particular, it is of interest to estimate how many new genes can be detected in a future EST sample of given size and also to determine the gene discovery rate: these estimates represent the basis for deciding whether to proceed sequencing the library and, in case of a positive decision, a guideline for selecting the size of the new sample. Such information is also useful for establishing sequencing efficiency in experimental design and for measuring the degree of redundancy of an EST library. Results In this work we propose a Bayesian nonparametric approach for tackling statistical problems related to EST surveys. In particular, we provide estimates for: a the coverage, defined as the proportion of unique genes in the library represented in the given sample of reads; b the number of new unique genes to be observed in a future sample; c the discovery rate of new genes as a function of the future sample size. The Bayesian nonparametric model we adopt conveys, in a statistically rigorous way, the available information into prediction. Our proposal has appealing properties over frequentist nonparametric methods, which become unstable when prediction is required for large future samples. EST libraries, previously studied with frequentist methods, are analyzed in detail. Conclusion The Bayesian nonparametric approach we undertake yields valuable tools for gene capture and prediction in EST libraries. The estimators we obtain do not feature the kind of drawbacks associated with frequentist estimators and are reliable for any size of the additional sample.

  16. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    OpenAIRE

    Noor Rashidah Rashid

    2012-01-01

    Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis tes...

  17. Categorical and nonparametric data analysis choosing the best statistical technique

    CERN Document Server

    Nussbaum, E Michael

    2014-01-01

    Featuring in-depth coverage of categorical and nonparametric statistics, this book provides a conceptual framework for choosing the most appropriate type of test in various research scenarios. Class tested at the University of Nevada, the book's clear explanations of the underlying assumptions, computer simulations, and Exploring the Concept boxes help reduce reader anxiety. Problems inspired by actual studies provide meaningful illustrations of the techniques. The underlying assumptions of each test and the factors that impact validity and statistical power are reviewed so readers can explain

  18. Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

    Science.gov (United States)

    Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

    2011-07-13

    Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

  19. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E. [Emory Univ. School of Public Health, Atlanta, GA (United States); Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1995-02-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of {open_quotes}susceptibility{close_quotes} alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes. 20 refs., 5 figs., 1 tab.

  20. Model-based methods for linkage analysis.

    Science.gov (United States)

    Rice, John P; Saccone, Nancy L; Corbett, Jonathan

    2008-01-01

    The logarithm of an odds ratio (LOD) score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential so that pedigrees or LOD curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders where the maximum LOD score statistic shares some of the advantages of the traditional LOD score approach, but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the LOD score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

  1. Local kernel nonparametric discriminant analysis for adaptive extraction of complex structures

    Science.gov (United States)

    Li, Quanbao; Wei, Fajie; Zhou, Shenghan

    2017-05-01

    The linear discriminant analysis (LDA) is one of popular means for linear feature extraction. It usually performs well when the global data structure is consistent with the local data structure. Other frequently-used approaches of feature extraction usually require linear, independence, or large sample condition. However, in real world applications, these assumptions are not always satisfied or cannot be tested. In this paper, we introduce an adaptive method, local kernel nonparametric discriminant analysis (LKNDA), which integrates conventional discriminant analysis with nonparametric statistics. LKNDA is adept in identifying both complex nonlinear structures and the ad hoc rule. Six simulation cases demonstrate that LKNDA have both parametric and nonparametric algorithm advantages and higher classification accuracy. Quartic unilateral kernel function may provide better robustness of prediction than other functions. LKNDA gives an alternative solution for discriminant cases of complex nonlinear feature extraction or unknown feature extraction. At last, the application of LKNDA in the complex feature extraction of financial market activities is proposed.

  2. Linkages among U.S. Treasury Bond Yields, Commodity Futures and Stock Market Implied Volatility: New Nonparametric Evidence

    Directory of Open Access Journals (Sweden)

    Vychytilova Jana

    2015-09-01

    Full Text Available This paper aims to explore specific cross-asset market correlations over the past fifteen- yearperiod-from January 04, 1999 till April 01, 2015, and within four sub-phases covering both the crisis and the non-crisis periods. On the basis of multivariate statistical methods, we focus on investigating relations between selected well-known market indices- U.S. treasury bond yields- the 30-year treasury yield index (TYX and the 10-year treasury yield (TNX; commodity futures the TR/J CRB; and implied volatility of S&P 500 index- the VIX. We estimate relative logarithmic returns by using monthly close prices adjusted for dividends and splits and run normality and correlation analyses. This paper indicates that the TR/J CRB can be adequately modeled by a normal distribution, whereas the rest of benchmarks do not come from a normal distribution. This paper, inter alia, points out some evidence of a statistically significant negative relationship between bond yields and the VIX in the past fifteen years and a statistically significant negative linkage between the TR/J CRB and the VIX since 2009. In rather general terms, this paper thereafter supports the a priori idea- financial markets are interconnected. Such knowledge can be beneficial for building and testing accurate financial market models, and particularly for the understanding and recognizing market cycles.

  3. Non-parametric production analysis of pesticides use in the Netherlands

    NARCIS (Netherlands)

    Oude Lansink, A.G.J.M.; Silva, E.

    2004-01-01

    Many previous empirical studies on the productivity of pesticides suggest that pesticides are under-utilized in agriculture despite the general held believe that these inputs are substantially over-utilized. This paper uses data envelopment analysis (DEA) to calculate non-parametric measures of the

  4. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E.; Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

  5. Comparison of Rank Analysis of Covariance and Nonparametric Randomized Blocks Analysis.

    Science.gov (United States)

    Porter, Andrew C.; McSweeney, Maryellen

    The relative power of three possible experimental designs under the condition that data is to be analyzed by nonparametric techniques; the comparison of the power of each nonparametric technique to its parametric analogue; and the comparison of relative powers using nonparametric and parametric techniques are discussed. The three nonparametric…

  6. Spline Nonparametric Regression Analysis of Stress-Strain Curve of Confined Concrete

    Directory of Open Access Journals (Sweden)

    Tavio Tavio

    2008-01-01

    Full Text Available Due to enormous uncertainties in confinement models associated with the maximum compressive strength and ductility of concrete confined by rectilinear ties, the implementation of spline nonparametric regression analysis is proposed herein as an alternative approach. The statistical evaluation is carried out based on 128 large-scale column specimens of either normal-or high-strength concrete tested under uniaxial compression. The main advantage of this kind of analysis is that it can be applied when the trend of relation between predictor and response variables are not obvious. The error in the analysis can, therefore, be minimized so that it does not depend on the assumption of a particular shape of the curve. This provides higher flexibility in the application. The results of the statistical analysis indicates that the stress-strain curves of confined concrete obtained from the spline nonparametric regression analysis proves to be in good agreement with the experimental curves available in literatures

  7. The Use of Nonparametric Kernel Regression Methods in Econometric Production Analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard

    This PhD thesis addresses one of the fundamental problems in applied econometric analysis, namely the econometric estimation of regression functions. The conventional approach to regression analysis is the parametric approach, which requires the researcher to specify the form of the regression...... to avoid this problem. The main objective is to investigate the applicability of the nonparametric kernel regression method in applied production analysis. The focus of the empirical analyses included in this thesis is the agricultural sector in Poland. Data on Polish farms are used to investigate...... practically and politically relevant problems and to illustrate how nonparametric regression methods can be used in applied microeconomic production analysis both in panel data and cross-section data settings. The thesis consists of four papers. The first paper addresses problems of parametric...

  8. Autosomal dominant familial spastic paraplegia; Linkage analysis and evidence for linkage to chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Figlewicz, D.A. [Univ. of Rochester, NY (United States); Dube, M.P.; Rouleau, G.A. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Familial spastic paraplegia (FSP) is a degenerative disorder of the motor system characterized by progressive weakness and spasticity of the lower limbs. Little is known about the pathophysiology of this disorder. FSP can be inherited as an autosomal dominant (AD), autosomal recessive, or X-linked trait. We have undertaken linkage analysis for a group of 36 AD FSP families from which we have collected blood samples from 427 individuals, including 148 affected individuals. Typing of polymorphic markers has allowed us to exclude more than 50% of the genome. Recently, linkage for AD FSP to a locus on chromosome 14q was reported. Our AD FSP kindreds were tested for linkage to markers spanning the 20 cM region between D14S69 and D14S66; however, we were not able to establish linkage for any of our families to chromosome 14. Lod scores suggestive of linkage for some AD FSP kindreds have been obtained for markers on chromosome 2p. We have tested seven polymorphic markers spanning the region between D2S405 and D2S177. Our highest aggregate lod score, including all families tested, was obtained at the locus D2S352: 2.4 at 20 cM. Results from HOMOG analysis for linkage heterogeneity will be reported.

  9. Multilevel Latent Class Analysis: Parametric and Nonparametric Models

    Science.gov (United States)

    Finch, W. Holmes; French, Brian F.

    2014-01-01

    Latent class analysis is an analytic technique often used in educational and psychological research to identify meaningful groups of individuals within a larger heterogeneous population based on a set of variables. This technique is flexible, encompassing not only a static set of variables but also longitudinal data in the form of growth mixture…

  10. Applications of non-parametric statistics and analysis of variance on sample variances

    Science.gov (United States)

    Myers, R. H.

    1981-01-01

    Nonparametric methods that are available for NASA-type applications are discussed. An attempt will be made here to survey what can be used, to attempt recommendations as to when each would be applicable, and to compare the methods, when possible, with the usual normal-theory procedures that are avavilable for the Gaussion analog. It is important here to point out the hypotheses that are being tested, the assumptions that are being made, and limitations of the nonparametric procedures. The appropriateness of doing analysis of variance on sample variances are also discussed and studied. This procedure is followed in several NASA simulation projects. On the surface this would appear to be reasonably sound procedure. However, difficulties involved center around the normality problem and the basic homogeneous variance assumption that is mase in usual analysis of variance problems. These difficulties discussed and guidelines given for using the methods.

  11. The Use of Nonparametric Kernel Regression Methods in Econometric Production Analysis

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard

    This PhD thesis addresses one of the fundamental problems in applied econometric analysis, namely the econometric estimation of regression functions. The conventional approach to regression analysis is the parametric approach, which requires the researcher to specify the form of the regression...... function. However, the a priori specification of a functional form involves the risk of choosing one that is not similar to the “true” but unknown relationship between the regressors and the dependent variable. This problem, known as parametric misspecification, can result in biased parameter estimates...... and nonparametric estimations of production functions in order to evaluate the optimal firm size. The second paper discusses the use of parametric and nonparametric regression methods to estimate panel data regression models. The third paper analyses production risk, price uncertainty, and farmers' risk preferences...

  12. Multi-Directional Non-Parametric Analysis of Agricultural Efficiency

    DEFF Research Database (Denmark)

    Balezentis, Tomas

    the Multi-Directional Efficiency Analysis approach, (iii) to account for uncertainties via the use of probabilistic and fuzzy measures. Therefore, the thesis encompass six papers dedicated to (the combinations of) these objectives. One of the main contributions of this thesis is a number of extensions...... relative to labour, intermediate consumption and land (in some cases land was not treated as a discretionary input). These findings call for further research on relationships among financial structure, investment decisions, and efficiency in Lithuanian family farms. Application of different techniques...

  13. Identifying marker typing incompatibilities in linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stringham, H.M.; Boehnke, M. [Univ. of Michigan, Ann Arbor, MI (United States)

    1996-10-01

    A common problem encountered in linkage analyses is that execution of the computer program is halted because of genotypes in the data that are inconsistent with Mendelian inheritance. Such inconsistencies may arise because of pedigree errors or errors in typing. In some cases, the source of the inconsistencies is easily identified by examining the pedigree. In others, the error is not obvious, and substantial time and effort are required to identify the responsible genotypes. We have developed two methods for automatically identifying those individuals whose genotypes are most likely the cause of the inconsistencies. First, we calculate the posterior probability of genotyping error for each member of the pedigree, given the marker data on all pedigree members and allowing anyone in the pedigree to have an error. Second, we identify those individuals whose genotypes could be solely responsible for the inconsistency in the pedigree. We illustrate these methods with two examples: one a pedigree error, the second a genotyping error. These methods have been implemented as a module of the pedigree analysis program package MENDEL. 9 refs., 2 figs., 2 tabs.

  14. Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray Time-Course Data.

    Science.gov (United States)

    Tan, Qihua; Thomassen, Mads; Burton, Mark; Mose, Kristian Fredløv; Andersen, Klaus Ejner; Hjelmborg, Jacob; Kruse, Torben

    2017-06-06

    Modeling complex time-course patterns is a challenging issue in microarray study due to complex gene expression patterns in response to the time-course experiment. We introduce the generalized correlation coefficient and propose a combinatory approach for detecting, testing and clustering the heterogeneous time-course gene expression patterns. Application of the method identified nonlinear time-course patterns in high agreement with parametric analysis. We conclude that the non-parametric nature in the generalized correlation analysis could be an useful and efficient tool for analyzing microarray time-course data and for exploring the complex relationships in the omics data for studying their association with disease and health.

  15. Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray Time-Course Data

    DEFF Research Database (Denmark)

    Tan, Qihua; Thomassen, Mads; Burton, Mark

    2017-01-01

    Modeling complex time-course patterns is a challenging issue in microarray study due to complex gene expression patterns in response to the time-course experiment. We introduce the generalized correlation coefficient and propose a combinatory approach for detecting, testing and clustering...... the heterogeneous time-course gene expression patterns. Application of the method identified nonlinear time-course patterns in high agreement with parametric analysis. We conclude that the non-parametric nature in the generalized correlation analysis could be an useful and efficient tool for analyzing microarray...... time-course data and for exploring the complex relationships in the omics data for studying their association with disease and health....

  16. Generalized Correlation Coefficient for Non-Parametric Analysis of Microarray Time-Course Data

    DEFF Research Database (Denmark)

    Tan, Qihua; Thomassen, Mads; Burton, Mark

    2017-01-01

    Modeling complex time-course patterns is a challenging issue in microarray study due to complex gene expression patterns in response to the time-course experiment. We introduce the generalized correlation coefficient and propose a combinatory approach for detecting, testing and clustering...... the heterogeneous time-course gene expression patterns. Application of the method identified nonlinear time-course patterns in high agreement with parametric analysis. We conclude that the non-parametric nature in the generalized correlation analysis could be an useful and efficient tool for analyzing microarray...

  17. ANALYSIS OF INTER SECTORAL LINKAGES IN SEMARANG REGENCY

    Directory of Open Access Journals (Sweden)

    Fafurida

    2014-03-01

    Full Text Available This research aims to analyze inter economic sectoral linkages and to arrange the Klassen typology of economic sectors in Semarang Regency. The Klassen typology is composed from the result of the linkage analysis. To construct the analysis, this paper also utulizes the input-output analysis. It finds that service sector has the highest backward linkage while farming sector has the highest forward linkage. Based on the Klassen typology analysis, sectors with the highest backward and forward linkages and potential to be the leading sector are farming sector, dan trade, hotel and restaurant sector.Keywords: Backward linkage,forward linkage, Klassen typologyJEL classification number: R15, O21AbstrakPenelitian ini bertujuan untuk mengkaji seberapa besar keterkaitan antar sektor ekonomi di Kabupaten Semarang dan memetakan tipologi Klassennya. Tipologi Klasen disusun berdasarkan hasil perhitungan analisis keterkaitannya. Untuk menyusun analisis tersebut, paper ini juga menggunakan analisis input-output. Hasil penelitian menunjukkan bahwa sektor jasa memiliki keterkaitan ke belakang tertinggi dibandingkan dengan sektor lainnya. Sementara itu, sektor pertanian merupakan sektor yang memiliki keterkaitan ke depan tertinggi. Berdasarkan hasil analisis tipologi Klassen, sektor yang memiliki keterkaitan ke depan dan ke belakang yang tinggi dan dapat menjadi sektor unggulan adalah sektor perdagangan, hotel dan sektor restoran.Kata kunci: Keterkaitan ke belakang, keterkaitan ke depan, tipologi KlassenJEL classification numbers: R15, O21

  18. Nonparametric bootstrap analysis with applications to demographic effects in demand functions.

    Science.gov (United States)

    Gozalo, P L

    1997-12-01

    "A new bootstrap proposal, labeled smooth conditional moment (SCM) bootstrap, is introduced for independent but not necessarily identically distributed data, where the classical bootstrap procedure fails.... A good example of the benefits of using nonparametric and bootstrap methods is the area of empirical demand analysis. In particular, we will be concerned with their application to the study of two important topics: what are the most relevant effects of household demographic variables on demand behavior, and to what extent present parametric specifications capture these effects." excerpt

  19. Nonparametric Bayesian Dictionary Learning for Analysis of Noisy and Incomplete Images

    Science.gov (United States)

    2010-04-01

    OF EACH CELL ARE RESULTS OF KSVD AND BPFA, RESPECTIVELY. σ C.man House Peppers Lena Barbara Boats F.print Couple Hill 5 37.87 39.37 37.78 38.60 38.08...INTERPOLATION PSNR RESULTS, USING PATCH SIZE 8× 8. BOTTOM: BPFA RGB IMAGE INTERPOLATION PSNR RESULTS, USING PATCH SIZE 7× 7. data ratio C.man House Peppers Lena...of subspaces. IEEE Trans. Inform. Theory, 2009. [16] T. Ferguson . A Bayesian analysis of some nonparametric problems. Annals of Statistics, 1:209–230

  20. An adaptive nonparametric method in benchmark analysis for bioassay and environmental studies.

    Science.gov (United States)

    Bhattacharya, Rabi; Lin, Lizhen

    2010-12-01

    We present a novel nonparametric method for bioassay and benchmark analysis in risk assessment, which averages isotonic MLEs based on disjoint subgroups of dosages. The asymptotic theory for the methodology is derived, showing that the MISEs (mean integrated squared error) of the estimates of both the dose-response curve F and its inverse F(-1) achieve the optimal rate O(N(-4/5)). Also, we compute the asymptotic distribution of the estimate ζ~p of the effective dosage ζ(p) = F(-1) (p) which is shown to have an optimally small asymptotic variance.

  1. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Science.gov (United States)

    Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

    2015-01-01

    Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  2. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Directory of Open Access Journals (Sweden)

    Anna L Mitchell

    Full Text Available Autoimmune Addison's disease (AAD is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18, on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls. The data were analysed using a meta-analysis approach.In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7. A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  3. Evolution of the CMB Power Spectrum Across WMAP Data Releases: A Nonparametric Analysis

    CERN Document Server

    Aghamousa, Amir; Souradeep, Tarun

    2011-01-01

    We present a comparative analysis of the WMAP 1-, 3-, 5-, and 7-year data releases for the CMB angular power spectrum, with respect to the following three key questions: (a) How well is the angular power spectrum determined by the data alone? (b) How well is the Lambda-CDM model supported by a model-independent, data-driven analysis? (c) What are the realistic uncertainties on peak/dip locations and heights? Our analysis is based on a nonparametric function estimation methodology [1,2]. Our results show that the height of the power spectrum is well determined by data alone for multipole index l approximately less than 600 (1-year), 800 (3-year), and 900 (5- and 7-year data realizations). We also show that parametric fits based on the Lambda-CDM model are remarkably close to our nonparametric fit in l-regions where the data are sufficiently precise. A contrasting example is provided by an H-Lambda-CDM model: As the data become precise with successive data realizations, the H-Lambda-CDM angular power spectrum g...

  4. Kinematic and Dynamic Characteristics Analysis of Bennett’ s Linkage

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Li

    2015-01-01

    Bennett’ s linkage is a spatial fourlink linkage, and has an extensive application prospect in the deployable linkages.Its kinematic and dynamic characteristics analysis has a great significance in its synthesis and application. According to the geometrical conditions of Bennett ’ s linkage, the motion equations are established,and the expressions of angular displacement, angular velocity and angular acceleration of the followers and the displacement, velocity and acceleration of mass center of link are shown. Based on Lagrange’ s equation, the multi⁃rigid⁃body dynamic model of Bennett’ s linkage is established. In order to solve the reaction forces and moments of joint, screw theory and reciprocal screw method are combined to establish the computing method.The number of equations and unknown reaction forces and moments of joint are equal through adding link deformation equations. The influence of the included angle of adjacent axes on Bennett ’ s linkage ’ s kinematic characteristics, the dynamic characteristics and the reaction forces and moments of joint are analyzed. Results show that the included angle of adjacent axes has a great effect on velocity, acceleration, the reaction forces and moments of Bennett’ s linkage. The change of reaction forces and moments of joint are apparent near the singularity configuration.

  5. Bayesian Nonparametric Regression Analysis of Data with Random Effects Covariates from Longitudinal Measurements

    KAUST Repository

    Ryu, Duchwan

    2010-09-28

    We consider nonparametric regression analysis in a generalized linear model (GLM) framework for data with covariates that are the subject-specific random effects of longitudinal measurements. The usual assumption that the effects of the longitudinal covariate processes are linear in the GLM may be unrealistic and if this happens it can cast doubt on the inference of observed covariate effects. Allowing the regression functions to be unknown, we propose to apply Bayesian nonparametric methods including cubic smoothing splines or P-splines for the possible nonlinearity and use an additive model in this complex setting. To improve computational efficiency, we propose the use of data-augmentation schemes. The approach allows flexible covariance structures for the random effects and within-subject measurement errors of the longitudinal processes. The posterior model space is explored through a Markov chain Monte Carlo (MCMC) sampler. The proposed methods are illustrated and compared to other approaches, the "naive" approach and the regression calibration, via simulations and by an application that investigates the relationship between obesity in adulthood and childhood growth curves. © 2010, The International Biometric Society.

  6. Bayesian nonparametric regression analysis of data with random effects covariates from longitudinal measurements.

    Science.gov (United States)

    Ryu, Duchwan; Li, Erning; Mallick, Bani K

    2011-06-01

    We consider nonparametric regression analysis in a generalized linear model (GLM) framework for data with covariates that are the subject-specific random effects of longitudinal measurements. The usual assumption that the effects of the longitudinal covariate processes are linear in the GLM may be unrealistic and if this happens it can cast doubt on the inference of observed covariate effects. Allowing the regression functions to be unknown, we propose to apply Bayesian nonparametric methods including cubic smoothing splines or P-splines for the possible nonlinearity and use an additive model in this complex setting. To improve computational efficiency, we propose the use of data-augmentation schemes. The approach allows flexible covariance structures for the random effects and within-subject measurement errors of the longitudinal processes. The posterior model space is explored through a Markov chain Monte Carlo (MCMC) sampler. The proposed methods are illustrated and compared to other approaches, the "naive" approach and the regression calibration, via simulations and by an application that investigates the relationship between obesity in adulthood and childhood growth curves.

  7. Towards Nonstationary, Nonparametric Independent Process Analysis with Unknown Source Component Dimensions

    CERN Document Server

    Szabo, Zoltan

    2010-01-01

    The goal of this paper is to extend independent subspace analysis (ISA) to the case of (i) nonparametric, not strictly stationary source dynamics and (ii) unknown source component dimensions. We make use of functional autoregressive (fAR) processes to model the temporal evolution of the hidden sources. An extension of the ISA separation principle--which states that the ISA problem can be solved by traditional independent component analysis (ICA) and clustering of the ICA elements--is derived for the solution of the defined fAR independent process analysis task (fAR-IPA): applying fAR identification we reduce the problem to ISA. A local averaging approach, the Nadaraya-Watson kernel regression technique is adapted to obtain strongly consistent fAR estimation. We extend the Amari-index to different dimensional components and illustrate the efficiency of the fAR-IPA approach by numerical examples.

  8. Inflammatory bowel disease gene hunting by linkage analysis: rationale, methodology, and present status of the field.

    Science.gov (United States)

    Brant, Steven R; Shugart, Yin Yao

    2004-05-01

    Observed inflammatory bowel disease (IBD) familial clustering and increased monozygotic twin concordance has led to the hypothesis that genetic loci containing IBD susceptibility genes can be identified by whole genome linkage mapping approaches. Methodology including collecting carefully phenotyped multiplex pedigrees, genotyping using highly informative microsatellite markers and linkage analysis by non-parametric allele sharing methods has been established. Eleven published genome wide screens (GWS) have studied more than 1,200 multiplex IBD pedigrees. Two-thirds of affected relative pairs were Crohn's disease (CD), 20% ulcerative colitis (UC) and the remaining were mixed. Seven loci (IBDI-7) on chromosomes 16q, 12, 6p, 14q, 5q, 19, and 1p have been identified with genome wide significant and independently replicated linkage. Risk alleles/haplotypes have been defined for the IBD1 (CARD15/NOD2), IBD3 (HLA) and IBD5 (5q cytokine cluster) loci. There has been evidence for a second chromosome 16 locus (IBD8) independent of NOD2 that overlaps IBD1 on the pericentromeric p-arm. Several other regions show great promise for containing additional IBD loci, particularly chromosome 3p with genome wide evidence in one study at 3p26 and more centromeric evidence in several other studies, and chromosomes 2q, 3q, 4q, 7, 11p, and Xp each with suggestive evidence of linkage in one and additional evidence in two or more studies. Single GWSs and fine mapping studies containing very large sets of pedigrees and in particular, more UC pedigrees, and the use of creative analytic and disease stratification schemes are required to identify, establish and refine weaker IBD loci.

  9. A Level Set Analysis and A Nonparametric Regression on S&P 500 Daily Return

    Directory of Open Access Journals (Sweden)

    Yipeng Yang

    2016-02-01

    Full Text Available In this paper, a level set analysis is proposed which aims to analyze the S&P 500 return with a certain magnitude. It is found that the process of large jumps/drops of return tend to have negative serial correlation, and volatility clustering phenomenon can be easily seen. Then, a nonparametric analysis is performed and new patterns are discovered. An ARCH model is constructed based on the patterns we discovered and it is capable of manifesting the volatility skew in option pricing. A comparison of our model with the GARCH(1,1 model is carried out. The explanation of the validity on our model through prospect theory is provided, and, as a novelty, we linked the volatility skew phenomenon to the prospect theory in behavioral finance.

  10. Non-parametric frequency analysis of extreme values for integrated disaster management considering probable maximum events

    Science.gov (United States)

    Takara, K. T.

    2015-12-01

    This paper describes a non-parametric frequency analysis method for hydrological extreme-value samples with a size larger than 100, verifying the estimation accuracy with a computer intensive statistics (CIS) resampling such as the bootstrap. Probable maximum values are also incorporated into the analysis for extreme events larger than a design level of flood control. Traditional parametric frequency analysis methods of extreme values include the following steps: Step 1: Collecting and checking extreme-value data; Step 2: Enumerating probability distributions that would be fitted well to the data; Step 3: Parameter estimation; Step 4: Testing goodness of fit; Step 5: Checking the variability of quantile (T-year event) estimates by the jackknife resampling method; and Step_6: Selection of the best distribution (final model). The non-parametric method (NPM) proposed here can skip Steps 2, 3, 4 and 6. Comparing traditional parameter methods (PM) with the NPM, this paper shows that PM often underestimates 100-year quantiles for annual maximum rainfall samples with records of more than 100 years. Overestimation examples are also demonstrated. The bootstrap resampling can do bias correction for the NPM and can also give the estimation accuracy as the bootstrap standard error. This NPM has advantages to avoid various difficulties in above-mentioned steps in the traditional PM. Probable maximum events are also incorporated into the NPM as an upper bound of the hydrological variable. Probable maximum precipitation (PMP) and probable maximum flood (PMF) can be a new parameter value combined with the NPM. An idea how to incorporate these values into frequency analysis is proposed for better management of disasters that exceed the design level. The idea stimulates more integrated approach by geoscientists and statisticians as well as encourages practitioners to consider the worst cases of disasters in their disaster management planning and practices.

  11. Asset Market Linkages in Crisis Periods

    NARCIS (Netherlands)

    P. Hartmann; S. Straetmans; C.G. de Vries (Casper)

    2001-01-01

    textabstractWe characterize asset return linkages during periods of stress by an extremal dependence measure. Contrary to correlation analysis, this non-parametric measure is not predisposed towards the normal distribution and can account for non-linear relationships. Our estimates for the G-5 count

  12. Asset Market Linkages in Crisis Periods

    NARCIS (Netherlands)

    P. Hartmann; S. Straetmans; C.G. de Vries (Casper)

    2001-01-01

    textabstractWe characterize asset return linkages during periods of stress by an extremal dependence measure. Contrary to correlation analysis, this non-parametric measure is not predisposed towards the normal distribution and can account for non-linear relationships. Our estimates for the G-5

  13. Statistical analysis using the Bayesian nonparametric method for irradiation embrittlement of reactor pressure vessels

    Science.gov (United States)

    Takamizawa, Hisashi; Itoh, Hiroto; Nishiyama, Yutaka

    2016-10-01

    In order to understand neutron irradiation embrittlement in high fluence regions, statistical analysis using the Bayesian nonparametric (BNP) method was performed for the Japanese surveillance and material test reactor irradiation database. The BNP method is essentially expressed as an infinite summation of normal distributions, with input data being subdivided into clusters with identical statistical parameters, such as mean and standard deviation, for each cluster to estimate shifts in ductile-to-brittle transition temperature (DBTT). The clusters typically depend on chemical compositions, irradiation conditions, and the irradiation embrittlement. Specific variables contributing to the irradiation embrittlement include the content of Cu, Ni, P, Si, and Mn in the pressure vessel steels, neutron flux, neutron fluence, and irradiation temperatures. It was found that the measured shifts of DBTT correlated well with the calculated ones. Data associated with the same materials were subdivided into the same clusters even if neutron fluences were increased.

  14. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes.

    Science.gov (United States)

    Silverman, Edwin K; Mosley, Jonathan D; Palmer, Lyle J; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-03-15

    Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV(1)) < 60% predicted, FEV(1)/FVC < 90% predicted], mild airflow obstruction (FEV(1) < 80% predicted, FEV(1)/FVC < 90% predicted) and chronic bronchitis. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow

  15. Typology of Empirical Attributes: Dissimilarity Linkage Analysis (DLA).

    Science.gov (United States)

    Dubin, Robert; Champoux, Joseph E.

    Dissimilarity Linkage Analysis (DLA) is an extremely simple procedure for developing a typology from empirical attributes that permits the clustering of entities. First the procedure develops a taxonomy of types from empirical attributes possessed by entities in the sample. Second, the procedure assigns entities to one, and only one, type in the…

  16. Trend Analysis of Golestan's Rivers Discharges Using Parametric and Non-parametric Methods

    Science.gov (United States)

    Mosaedi, Abolfazl; Kouhestani, Nasrin

    2010-05-01

    One of the major problems in human life is climate changes and its problems. Climate changes will cause changes in rivers discharges. The aim of this research is to investigate the trend analysis of seasonal and yearly rivers discharges of Golestan province (Iran). In this research four trend analysis method including, conjunction point, linear regression, Wald-Wolfowitz and Mann-Kendall, for analyzing of river discharges in seasonal and annual periods in significant level of 95% and 99% were applied. First, daily discharge data of 12 hydrometrics stations with a length of 42 years (1965-2007) were selected, after some common statistical tests such as, homogeneity test (by applying G-B and M-W tests), the four mentioned trends analysis tests were applied. Results show that in all stations, for summer data time series, there are decreasing trends with a significant level of 99% according to Mann-Kendall (M-K) test. For autumn time series data, all four methods have similar results. For other periods, the results of these four tests were more or less similar together. While, for some stations the results of tests were different. Keywords: Trend Analysis, Discharge, Non-parametric methods, Wald-Wolfowitz, The Mann-Kendall test, Golestan Province.

  17. Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.

    Directory of Open Access Journals (Sweden)

    Abra Brisbin

    Full Text Available BACKGROUND: Pedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data. METHODOLOGY: We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate that can analyze complex genealogical structure for family groups and incorporate missing data. LOCate uses a Gibbs sampling approach to assess linkage, incorporating a simulated tempering algorithm for fast mixing. While our treatment is Bayesian, we develop a LOD (log of odds score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulated data. LOCate is applicable to linkage analysis for ordinal or nominal traits, a versatility which we demonstrate by analyzing simulated data with a nominal trait, on which LOCate outperforms LOT, an existing method which is designed for ordinal traits. We additionally demonstrate our method's versatility by analyzing a candidate locus (D2S1788 for panic disorder in humans, in a dataset with a large amount of missing data, which LOT was unable to handle. CONCLUSION: LOCate's accuracy and applicability to both ordinal and nominal traits will prove useful to researchers interested in mapping loci for categorical traits.

  18. Broad scan linkage analysis in a large Tourette family pedigree

    Energy Technology Data Exchange (ETDEWEB)

    Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

    1994-09-01

    Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

  19. LINKAGE ANALYSIS BY 2-DIMENSIONAL DNA TYPING

    NARCIS (Netherlands)

    MEERMAN, GJT; MULLAART, E; VANDERMEULEN, MA; DENDAAS, JHG; MOROLLI, B; UITTERLINDEN, AG; VIJG, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core pro

  20. Asymptotic estimation theory of multipoint linkage analysis under perfect marker information

    OpenAIRE

    Hössjer, Ola

    2003-01-01

    We consider estimation of a disease susceptibility locus $\\tau$ at a chromosome. With perfect marker data available, the estimator $\\htau_N$ of $\\tau$ based on $N$-pedigrees has a rate of convergence $N^{-1}$ under mild regularity conditions. The limiting distribution is the arg max of a certain compound Poisson process. Our approach is conditional on observed phenotypes, and therefore treats parametric and nonparametric linkage, as well as quantitative trait loci methods within a unified fra...

  1. APPLICATION OF PARAMETRIC AND NON-PARAMETRIC BENCHMARKING METHODS IN COST EFFICIENCY ANALYSIS OF THE ELECTRICITY DISTRIBUTION SECTOR

    Directory of Open Access Journals (Sweden)

    Andrea Furková

    2007-06-01

    Full Text Available This paper explores the aplication of parametric and non-parametric benchmarking methods in measuring cost efficiency of Slovak and Czech electricity distribution companies. We compare the relative cost efficiency of Slovak and Czech distribution companies using two benchmarking methods: the non-parametric Data Envelopment Analysis (DEA and the Stochastic Frontier Analysis (SFA as the parametric approach. The first part of analysis was based on DEA models. Traditional cross-section CCR and BCC model were modified to cost efficiency estimation. In further analysis we focus on two versions of stochastic frontier cost functioin using panel data: MLE model and GLS model. These models have been applied to an unbalanced panel of 11 (Slovakia 3 and Czech Republic 8 regional electricity distribution utilities over a period from 2000 to 2004. The differences in estimated scores, parameters and ranking of utilities were analyzed. We observed significant differences between parametric methods and DEA approach.

  2. European regional efficiency and geographical externalities: a spatial nonparametric frontier analysis

    Science.gov (United States)

    Ramajo, Julián; Cordero, José Manuel; Márquez, Miguel Ángel

    2017-10-01

    This paper analyses region-level technical efficiency in nine European countries over the 1995-2007 period. We propose the application of a nonparametric conditional frontier approach to account for the presence of heterogeneous conditions in the form of geographical externalities. Such environmental factors are beyond the control of regional authorities, but may affect the production function. Therefore, they need to be considered in the frontier estimation. Specifically, a spatial autoregressive term is included as an external conditioning factor in a robust order- m model. Thus we can test the hypothesis of non-separability (the external factor impacts both the input-output space and the distribution of efficiencies), demonstrating the existence of significant global interregional spillovers into the production process. Our findings show that geographical externalities affect both the frontier level and the probability of being more or less efficient. Specifically, the results support the fact that the spatial lag variable has an inverted U-shaped non-linear impact on the performance of regions. This finding can be interpreted as a differential effect of interregional spillovers depending on the size of the neighboring economies: positive externalities for small values, possibly related to agglomeration economies, and negative externalities for high values, indicating the possibility of production congestion. Additionally, evidence of the existence of a strong geographic pattern of European regional efficiency is reported and the levels of technical efficiency are acknowledged to have converged during the period under analysis.

  3. Identification of quantitative trait loci underlying milk traits in Spanish dairy sheep using linkage plus combined linkage disequilibrium and linkage analysis approaches.

    Science.gov (United States)

    Garcia-Gámez, E; Gutiérrez-Gil, B; Suarez-Vega, A; de la Fuente, L F; Arranz, J J

    2013-09-01

    In this study, 2 procedures were used to analyze a data set from a whole-genome scan, one based on linkage analysis information and the other combing linkage disequilibrium and linkage analysis (LDLA), to determine the quantitative trait loci (QTL) influencing milk production traits in sheep. A total of 1,696 animals from 16 half-sib families were genotyped using the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA) and analysis was performed using a daughter design. Moreover, the same data set has been previously investigated through a genome-wide association (GWA) analysis and a comparison of results from the 3 methods has been possible. The linkage analysis and LDLA methodologies yielded different results, although some significantly associated regions were common to both procedures. The linkage analysis detected 3 overlapping genome-wise significant QTL on sheep chromosome (OAR) 2 influencing milk yield, protein yield, and fat yield, whereas 34 genome-wise significant QTL regions were detected using the LDLA approach. The most significant QTL for protein and fat percentages was detected on OAR3, which was reported in a previous GWA analysis. Both the linkage analysis and LDLA identified many other chromosome-wise significant associations across different sheep autosomes. Additional analyses were performed on OAR2 and OAR3 to determine the possible causality of the most significant polymorphisms identified for these genetic effects by the previously reported GWA analysis. For OAR3, the analyses demonstrated additional genetic proof of the causality previously suggested by our group for a single nucleotide polymorphism located in the α-lactalbumin gene (LALBA). In summary, although the results shown here suggest that in commercial dairy populations, the LDLA method exhibits a higher efficiency to map QTL than the simple linkage analysis or linkage disequilibrium methods, we believe that comparing the 3 analysis methods is the best approach to obtain a global

  4. Non-parametric seismic hazard analysis in the presence of incomplete data

    Science.gov (United States)

    Yazdani, Azad; Mirzaei, Sajjad; Dadkhah, Koroush

    2017-01-01

    The distribution of earthquake magnitudes plays a crucial role in the estimation of seismic hazard parameters. Due to the complexity of earthquake magnitude distribution, non-parametric approaches are recommended over classical parametric methods. The main deficiency of the non-parametric approach is the lack of complete magnitude data in almost all cases. This study aims to introduce an imputation procedure for completing earthquake catalog data that will allow the catalog to be used for non-parametric density estimation. Using a Monte Carlo simulation, the efficiency of introduced approach is investigated. This study indicates that when a magnitude catalog is incomplete, the imputation procedure can provide an appropriate tool for seismic hazard assessment. As an illustration, the imputation procedure was applied to estimate earthquake magnitude distribution in Tehran, the capital city of Iran.

  5. Analysis of intravenous glucose tolerance test data using parametric and nonparametric modeling: application to a population at risk for diabetes.

    Science.gov (United States)

    Marmarelis, Vasilis Z; Shin, Dae C; Zhang, Yaping; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2013-07-01

    Modeling studies of the insulin-glucose relationship have mainly utilized parametric models, most notably the minimal model (MM) of glucose disappearance. This article presents results from the comparative analysis of the parametric MM and a nonparametric Laguerre based Volterra Model (LVM) applied to the analysis of insulin modified (IM) intravenous glucose tolerance test (IVGTT) data from a clinical study of gestational diabetes mellitus (GDM). An IM IVGTT study was performed 8 to 10 weeks postpartum in 125 women who were diagnosed with GDM during their pregnancy [population at risk of developing diabetes (PRD)] and in 39 control women with normal pregnancies (control subjects). The measured plasma glucose and insulin from the IM IVGTT in each group were analyzed via a population analysis approach to estimate the insulin sensitivity parameter of the parametric MM. In the nonparametric LVM analysis, the glucose and insulin data were used to calculate the first-order kernel, from which a diagnostic scalar index representing the integrated effect of insulin on glucose was derived. Both the parametric MM and nonparametric LVM describe the glucose concentration data in each group with good fidelity, with an improved measured versus predicted r² value for the LVM of 0.99 versus 0.97 for the MM analysis in the PRD. However, application of the respective diagnostic indices of the two methods does result in a different classification of 20% of the individuals in the PRD. It was found that the data based nonparametric LVM revealed additional insights about the manner in which infused insulin affects blood glucose concentration. © 2013 Diabetes Technology Society.

  6. Linkage analysis on chromosome 2 in essential hypotension pedigrees

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is a new approach to study the important genes related to the control of blood pressure by probing into hypotension and hypertension at the same time. Genome scanning on whole chromosome 2 in 8 hypotension pedigrees has been done and parameter (LOD score) and non-pa- rameter (NPL score) were used in the linkage analysis by GENEHUNTER software. The results show the evidence of linkage between D2S112 and D2S117, indicating a number of critical genes may lie in thisregion and contribute to the mechanism of blood pressure regulation. Also this region has been found in the previous study in hypertension pedigrees. These genes may play an important role in the regulation of blood pressure and can also be the important candidate genes in hypertension studies.

  7. Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

  8. Genome-wide linkage analysis of inguinal hernia in pigs using affected sib pairs

    Directory of Open Access Journals (Sweden)

    Taubert Helge

    2006-05-01

    Full Text Available Abstract Background Inguinal and scrotal hernias are of great concern to pig producers, and lead to poor animal welfare and severe economic loss. Selection against these conditions is highly preferable, but at this time no gene, Quantitative Trait Loci (QTL, or mode of inheritance has been identified in pigs or in any other species. Therefore, a complete genome scan was performed in order to identify genomic regions affecting inguinal and scrotal hernias in pigs. Records from seedstock breeding farms were collected. No clinical examinations were executed on the pigs and there was therefore no distinction between inguinal and scrotal hernias. The genome scan utilised affected sib pairs (ASP, and the data was analysed using both an ASP test based on Non-parametric Linkage (NPL analysis, and a Transmission Disequilibrium Test (TDT. Results Significant QTLs (p Conclusion For the first time in any species, a genome scan has revealed suggestive QTLs for inguinal and scrotal hernias. While this study permitted the detection of chromosomal regions only, it is interesting to note that several promising candidate genes, including INSL3, MIS, and CGRP, are located within the highly significant QTL regions. Further studies are required in order to narrow down the suggestive QTL regions, investigate the candidate genes, and to confirm the suggestive QTLs in other populations. The haplotype associated with inguinal and scrotal hernias may help in achieving selection against the disorder.

  9. An exact predictive recursion for Bayesian nonparametric analysis of incomplete data

    OpenAIRE

    Garibaldi, Ubaldo; Viarengo, Paolo

    2010-01-01

    This paper presents a new derivation of nonparametric distribution estimation with right-censored data. It is based on an extension of the predictive inferences to compound evidence. The estimate is recursive and exact, and no stochastic approximation is needed: it simply requires that the censored data are processed in decreasing order. Only in this case the recursion provides exact posterior predictive distributions for subsequent samples under a Dirichlet process prior. The resulting estim...

  10. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  11. A Conservative Meta-Analysis of Linkage and Linkage-Association Studies of Developmental Dyslexia

    Science.gov (United States)

    Grigorenko, Elena L.

    2005-01-01

    Linkage studies of complex phenotypes such as reading ability/disability (developmental dyslexia or reading disorder) and related componential processes, where the effects attributable to individual genes appear to be modest, are critically dependent on the nature and composition of the samples and the phenotypes analyzed. Thus, it might be…

  12. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    Science.gov (United States)

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide Pgenetically tractable and provide insight into the genetic architecture of complex traits.

  13. CURRENT STATUS OF NONPARAMETRIC STATISTICS

    Directory of Open Access Journals (Sweden)

    Orlov A. I.

    2015-02-01

    Full Text Available Nonparametric statistics is one of the five points of growth of applied mathematical statistics. Despite the large number of publications on specific issues of nonparametric statistics, the internal structure of this research direction has remained undeveloped. The purpose of this article is to consider its division into regions based on the existing practice of scientific activity determination of nonparametric statistics and classify investigations on nonparametric statistical methods. Nonparametric statistics allows to make statistical inference, in particular, to estimate the characteristics of the distribution and testing statistical hypotheses without, as a rule, weakly proven assumptions about the distribution function of samples included in a particular parametric family. For example, the widespread belief that the statistical data are often have the normal distribution. Meanwhile, analysis of results of observations, in particular, measurement errors, always leads to the same conclusion - in most cases the actual distribution significantly different from normal. Uncritical use of the hypothesis of normality often leads to significant errors, in areas such as rejection of outlying observation results (emissions, the statistical quality control, and in other cases. Therefore, it is advisable to use nonparametric methods, in which the distribution functions of the results of observations are imposed only weak requirements. It is usually assumed only their continuity. On the basis of generalization of numerous studies it can be stated that to date, using nonparametric methods can solve almost the same number of tasks that previously used parametric methods. Certain statements in the literature are incorrect that nonparametric methods have less power, or require larger sample sizes than parametric methods. Note that in the nonparametric statistics, as in mathematical statistics in general, there remain a number of unresolved problems

  14. Nonparametric variance estimation in the analysis of microarray data: a measurement error approach.

    Science.gov (United States)

    Carroll, Raymond J; Wang, Yuedong

    2008-01-01

    This article investigates the effects of measurement error on the estimation of nonparametric variance functions. We show that either ignoring measurement error or direct application of the simulation extrapolation, SIMEX, method leads to inconsistent estimators. Nevertheless, the direct SIMEX method can reduce bias relative to a naive estimator. We further propose a permutation SIMEX method which leads to consistent estimators in theory. The performance of both SIMEX methods depends on approximations to the exact extrapolants. Simulations show that both SIMEX methods perform better than ignoring measurement error. The methodology is illustrated using microarray data from colon cancer patients.

  15. Non-parametric trend analysis of water quality data of rivers in Kansas

    Science.gov (United States)

    Yu, Y.-S.; Zou, S.; Whittemore, D.

    1993-01-01

    Surface water quality data for 15 sampling stations in the Arkansas, Verdigris, Neosho, and Walnut river basins inside the state of Kansas were analyzed to detect trends (or lack of trends) in 17 major constituents by using four different non-parametric methods. The results show that concentrations of specific conductance, total dissolved solids, calcium, total hardness, sodium, potassium, alkalinity, sulfate, chloride, total phosphorus, ammonia plus organic nitrogen, and suspended sediment generally have downward trends. Some of the downward trends are related to increases in discharge, while others could be caused by decreases in pollution sources. Homogeneity tests show that both station-wide trends and basinwide trends are non-homogeneous. ?? 1993.

  16. Association and linkage analysis of aluminum tolerance genes in maize.

    Directory of Open Access Journals (Sweden)

    Allison M Krill

    Full Text Available BACKGROUND: Aluminum (Al toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. METHODOLOGY: An association panel of 282 diverse maize inbred lines and three F2 linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis. CONCLUSIONS: Six candidate genes had significant results from association analysis, but only four were confirmed by linkage analysis as putatively contributing to Al tolerance: Zea mays AltSB like (ZmASL, Zea mays aluminum-activated malate transporter2 (ALMT2, S-adenosyl-L-homocysteinase (SAHH, and Malic Enzyme (ME. These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs.

  17. Hierarchical Cluster Analysis: Comparison of Three Linkage Measures and Application to Psychological Data

    Directory of Open Access Journals (Sweden)

    Odilia Yim

    2015-02-01

    Full Text Available Cluster analysis refers to a class of data reduction methods used for sorting cases, observations, or variables of a given dataset into homogeneous groups that differ from each other. The present paper focuses on hierarchical agglomerative cluster analysis, a statistical technique where groups are sequentially created by systematically merging similar clusters together, as dictated by the distance and linkage measures chosen by the researcher. Specific distance and linkage measures are reviewed, including a discussion of how these choices can influence the clustering process by comparing three common linkage measures (single linkage, complete linkage, average linkage. The tutorial guides researchers in performing a hierarchical cluster analysis using the SPSS statistical software. Through an example, we demonstrate how cluster analysis can be used to detect meaningful subgroups in a sample of bilinguals by examining various language variables.

  18. Robust non-parametric one-sample tests for the analysis of recurrent events.

    Science.gov (United States)

    Rebora, Paola; Galimberti, Stefania; Valsecchi, Maria Grazia

    2010-12-30

    One-sample non-parametric tests are proposed here for inference on recurring events. The focus is on the marginal mean function of events and the basis for inference is the standardized distance between the observed and the expected number of events under a specified reference rate. Different weights are considered in order to account for various types of alternative hypotheses on the mean function of the recurrent events process. A robust version and a stratified version of the test are also proposed. The performance of these tests was investigated through simulation studies under various underlying event generation processes, such as homogeneous and nonhomogeneous Poisson processes, autoregressive and renewal processes, with and without frailty effects. The robust versions of the test have been shown to be suitable in a wide variety of event generating processes. The motivating context is a study on gene therapy in a very rare immunodeficiency in children, where a major end-point is the recurrence of severe infections. Robust non-parametric one-sample tests for recurrent events can be useful to assess efficacy and especially safety in non-randomized studies or in epidemiological studies for comparison with a standard population.

  19. Importance sampling. I. Computing multimodel p values in linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kong, A.; Frigge, M.; Irwin, M.; Cox, N. (Univ. of Chicago, IL (United States))

    1992-12-01

    In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. The authors propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of their method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation. 22 refs., 6 figs., 1 tab.

  20. Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis.

    Science.gov (United States)

    Cox, D G; Canzian, F

    2001-08-01

    The purpose of this work is to provide the modern molecular geneticist with tools to perform more efficient and more accurate analysis of the genotype data they produce. By using Microsoft Excel macros written in Visual Basic, we can translate genotype data into a form readable by the versatile software 'Arlequin', read the Arlequin output, calculate statistics of linkage disequilibrium, and put the results in a format for viewing with the software 'GOLD'. The software is available by FTP at: ftp://xcsg.iarc.fr/cox/Genotype_Transposer/. Detailed instruction and examples are available at: ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at: http://lgb.unige.ch/arlequin/. GOLD is available at: http://www.well.ox.ac.uk/asthma/GOLD/.

  1. NParCov3: A SAS/IML Macro for Nonparametric Randomization-Based Analysis of Covariance

    Directory of Open Access Journals (Sweden)

    Richard C. Zink

    2012-07-01

    Full Text Available Analysis of covariance serves two important purposes in a randomized clinical trial. First, there is a reduction of variance for the treatment effect which provides more powerful statistical tests and more precise confidence intervals. Second, it provides estimates of the treatment effect which are adjusted for random imbalances of covariates between the treatment groups. The nonparametric analysis of covariance method of Koch, Tangen, Jung, and Amara (1998 defines a very general methodology using weighted least-squares to generate covariate-adjusted treatment effects with minimal assumptions. This methodology is general in its applicability to a variety of outcomes, whether continuous, binary, ordinal, incidence density or time-to-event. Further, its use has been illustrated in many clinical trial settings, such as multi-center, dose-response and non-inferiority trials.NParCov3 is a SAS/IML macro written to conduct the nonparametric randomization-based covariance analyses of Koch et al. (1998. The software can analyze a variety of outcomes and can account for stratification. Data from multiple clinical trials will be used for illustration.

  2. Nonparametric statistical inference

    CERN Document Server

    Gibbons, Jean Dickinson

    2014-01-01

    Thoroughly revised and reorganized, the fourth edition presents in-depth coverage of the theory and methods of the most widely used nonparametric procedures in statistical analysis and offers example applications appropriate for all areas of the social, behavioral, and life sciences. The book presents new material on the quantiles, the calculation of exact and simulated power, multiple comparisons, additional goodness-of-fit tests, methods of analysis of count data, and modern computer applications using MINITAB, SAS, and STATXACT. It includes tabular guides for simplified applications of tests and finding P values and confidence interval estimates.

  3. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus

    2013-01-01

    sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2...

  4. Nonparametric analysis of competing risks data with event category missing at random.

    Science.gov (United States)

    Gouskova, Natalia A; Lin, Feng-Chang; Fine, Jason P

    2017-03-01

    In competing risks setup, the data for each subject consist of the event time, censoring indicator, and event category. However, sometimes the information about the event category can be missing, as, for example, in a case when the date of death is known but the cause of death is not available. In such situations, treating subjects with missing event category as censored leads to the underestimation of the hazard functions. We suggest nonparametric estimators for the cumulative cause-specific hazards and the cumulative incidence functions which use the Nadaraya-Watson estimator to obtain the contribution of an event with missing category to each of the cause-specific hazards. We derive the propertied of the proposed estimators. Optimal bandwidth is determined, which minimizes the mean integrated squared errors of the proposed estimators over time. The methodology is illustrated using data on lung infections in patients from the United States Cystic Fibrosis Foundation Patient Registry. © 2016, The International Biometric Society.

  5. Nonparametric Signal Extraction and Measurement Error in the Analysis of Electroencephalographic Activity During Sleep.

    Science.gov (United States)

    Crainiceanu, Ciprian M; Caffo, Brian S; Di, Chong-Zhi; Punjabi, Naresh M

    2009-06-01

    We introduce methods for signal and associated variability estimation based on hierarchical nonparametric smoothing with application to the Sleep Heart Health Study (SHHS). SHHS is the largest electroencephalographic (EEG) collection of sleep-related data, which contains, at each visit, two quasi-continuous EEG signals for each subject. The signal features extracted from EEG data are then used in second level analyses to investigate the relation between health, behavioral, or biometric outcomes and sleep. Using subject specific signals estimated with known variability in a second level regression becomes a nonstandard measurement error problem. We propose and implement methods that take into account cross-sectional and longitudinal measurement error. The research presented here forms the basis for EEG signal processing for the SHHS.

  6. Nonparametric analysis of the time structure of seismicity in a geographic region

    Directory of Open Access Journals (Sweden)

    A. Quintela-del-Río

    2002-06-01

    Full Text Available As an alternative to traditional parametric approaches, we suggest nonparametric methods for analyzing temporal data on earthquake occurrences. In particular, the kernel method for estimating the hazard function and the intensity function are presented. One novelty of our approaches is that we take into account the possible dependence of the data to estimate the distribution of time intervals between earthquakes, which has not been considered in most statistics studies on seismicity. Kernel estimation of hazard function has been used to study the occurrence process of cluster centers (main shocks. Kernel intensity estimation, on the other hand, has helped to describe the occurrence process of cluster members (aftershocks. Similar studies in two geographic areas of Spain (Granada and Galicia have been carried out to illustrate the estimation methods suggested.

  7. Climatic, parametric and non-parametric analysis of energy performance of double-glazed windows in different climates

    Directory of Open Access Journals (Sweden)

    Saeed Banihashemi

    2015-12-01

    Full Text Available In line with the growing global trend toward energy efficiency in buildings, this paper aims to first; investigate the energy performance of double-glazed windows in different climates and second; analyze the most dominant used parametric and non-parametric tests in dimension reduction for simulating this component. A four-story building representing the conventional type of residential apartments for four climates of cold, temperate, hot-arid and hot-humid was selected for simulation. 10 variables of U-factor, SHGC, emissivity, visible transmittance, monthly average dry bulb temperature, monthly average percent humidity, monthly average wind speed, monthly average direct solar radiation, monthly average diffuse solar radiation and orientation constituted the parameters considered in the calculation of cooling and heating loads of the case. Design of Experiment and Principal Component Analysis methods were applied to find the most significant factors and reduction dimension of initial variables. It was observed that in two climates of temperate and hot-arid, using double glazed windows was beneficial in both cold and hot months whereas in cold and hot-humid climates where heating and cooling loads are dominant respectively, they were advantageous in only those dominant months. Furthermore, an inconsistency was revealed between parametric and non-parametric tests in terms of identifying the most significant variables.

  8. 'nparACT' package for R: A free software tool for the non-parametric analysis of actigraphy data.

    Science.gov (United States)

    Blume, Christine; Santhi, Nayantara; Schabus, Manuel

    2016-01-01

    For many studies, participants' sleep-wake patterns are monitored and recorded prior to, during and following an experimental or clinical intervention using actigraphy, i.e. the recording of data generated by movements. Often, these data are merely inspected visually without computation of descriptive parameters, in part due to the lack of user-friendly software. To address this deficit, we developed a package for R Core Team [6], that allows computing several non-parametric measures from actigraphy data. Specifically, it computes the interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of activity and gives the start times and average activity values of M10 (i.e. the ten hours with maximal activity) and L5 (i.e. the five hours with least activity). Two functions compute these 'classical' parameters and handle either single or multiple files. Two other functions additionally allow computing an L-value (i.e. the least activity value) for a user-defined time span termed 'Lflex' value. A plotting option is included in all functions. The package can be downloaded from the Comprehensive R Archives Network (CRAN). •The package 'nparACT' for R serves the non-parametric analysis of actigraphy data.•Computed parameters include interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) as well as start times and average activity during the 10 h with maximal and the 5 h with minimal activity (i.e. M10 and L5).

  9. Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-05-01

    Full Text Available Abstract A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

  10. Genomewide Linkage Analysis of Bipolar Disorder by Use of a High-Density Single-Nucleotide–Polymorphism (SNP) Genotyping Assay: A Comparison with Microsatellite Marker Assays and Finding of Significant Linkage to Chromosome 6q22

    Science.gov (United States)

    Middleton, F. A.; Pato, M. T.; Gentile, K. L.; Morley, C. P.; Zhao, X.; Eisener, A. F.; Brown, A.; Petryshen, T. L.; Kirby, A. N.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.; Valente, J.; Soares, M. J.; Ferreira, C. P.; Lei, M.; Azevedo, M. H.; Kennedy, J. L.; Daly, M. J.; Sklar, P.; Pato, C. N.

    2004-01-01

    We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11. PMID:15060841

  11. Nonparametric statistics for social and behavioral sciences

    CERN Document Server

    Kraska-MIller, M

    2013-01-01

    Introduction to Research in Social and Behavioral SciencesBasic Principles of ResearchPlanning for ResearchTypes of Research Designs Sampling ProceduresValidity and Reliability of Measurement InstrumentsSteps of the Research Process Introduction to Nonparametric StatisticsData AnalysisOverview of Nonparametric Statistics and Parametric Statistics Overview of Parametric Statistics Overview of Nonparametric StatisticsImportance of Nonparametric MethodsMeasurement InstrumentsAnalysis of Data to Determine Association and Agreement Pearson Chi-Square Test of Association and IndependenceContingency

  12. A statistical design for testing apomictic diversification through linkage analysis.

    Science.gov (United States)

    Zeng, Yanru; Hou, Wei; Song, Shuang; Feng, Sisi; Shen, Lin; Xia, Guohua; Wu, Rongling

    2014-03-01

    The capacity of apomixis to generate maternal clones through seed reproduction has made it a useful characteristic for the fixation of heterosis in plant breeding. It has been observed that apomixis displays pronounced intra- and interspecific diversification, but the genetic mechanisms underlying this diversification remains elusive, obstructing the exploitation of this phenomenon in practical breeding programs. By capitalizing on molecular information in mapping populations, we describe and assess a statistical design that deploys linkage analysis to estimate and test the pattern and extent of apomictic differences at various levels from genotypes to species. The design is based on two reciprocal crosses between two individuals each chosen from a hermaphrodite or monoecious species. A multinomial distribution likelihood is constructed by combining marker information from two crosses. The EM algorithm is implemented to estimate the rate of apomixis and test its difference between two plant populations or species as the parents. The design is validated by computer simulation. A real data analysis of two reciprocal crosses between hickory (Carya cathayensis) and pecan (C. illinoensis) demonstrates the utilization and usefulness of the design in practice. The design provides a tool to address fundamental and applied questions related to the evolution and breeding of apomixis.

  13. Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs

    Directory of Open Access Journals (Sweden)

    Lannfelt Lars

    2009-12-01

    Full Text Available Abstract Background Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods In the present study, we have combined a selection of affected relative pairs (ARPs from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002, with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.

  14. Nonparametric randomization-based covariate adjustment for stratified analysis of time-to-event or dichotomous outcomes.

    Science.gov (United States)

    Hussey, Michael A; Koch, Gary G; Preisser, John S; Saville, Benjamin R

    2016-01-01

    Time-to-event or dichotomous outcomes in randomized clinical trials often have analyses using the Cox proportional hazards model or conditional logistic regression, respectively, to obtain covariate-adjusted log hazard (or odds) ratios. Nonparametric Randomization-Based Analysis of Covariance (NPANCOVA) can be applied to unadjusted log hazard (or odds) ratios estimated from a model containing treatment as the only explanatory variable. These adjusted estimates are stratified population-averaged treatment effects and only require a valid randomization to the two treatment groups and avoid key modeling assumptions (e.g., proportional hazards in the case of a Cox model) for the adjustment variables. The methodology has application in the regulatory environment where such assumptions cannot be verified a priori. Application of the methodology is illustrated through three examples on real data from two randomized trials.

  15. Transit Timing Observations from Kepler: II. Confirmation of Two Multiplanet Systems via a Non-parametric Correlation Analysis

    CERN Document Server

    Ford, Eric B; Steffen, Jason H; Carter, Joshua A; Fressin, Francois; Holman, Matthew J; Lissauer, Jack J; Moorhead, Althea V; Morehead, Robert C; Ragozzine, Darin; Rowe, Jason F; Welsh, William F; Allen, Christopher; Batalha, Natalie M; Borucki, William J; Bryson, Stephen T; Buchhave, Lars A; Burke, Christopher J; Caldwell, Douglas A; Charbonneau, David; Clarke, Bruce D; Cochran, William D; Désert, Jean-Michel; Endl, Michael; Everett, Mark E; Fischer, Debra A; Gautier, Thomas N; Gilliland, Ron L; Jenkins, Jon M; Haas, Michael R; Horch, Elliott; Howell, Steve B; Ibrahim, Khadeejah A; Isaacson, Howard; Koch, David G; Latham, David W; Li, Jie; Lucas, Philip; MacQueen, Phillip J; Marcy, Geoffrey W; McCauliff, Sean; Mullally, Fergal R; Quinn, Samuel N; Quintana, Elisa; Shporer, Avi; Still, Martin; Tenenbaum, Peter; Thompson, Susan E; Torres, Guillermo; Twicken, Joseph D; Wohler, Bill

    2012-01-01

    We present a new method for confirming transiting planets based on the combination of transit timingn variations (TTVs) and dynamical stability. Correlated TTVs provide evidence that the pair of bodies are in the same physical system. Orbital stability provides upper limits for the masses of the transiting companions that are in the planetary regime. This paper describes a non-parametric technique for quantifying the statistical significance of TTVs based on the correlation of two TTV data sets. We apply this method to an analysis of the transit timing variations of two stars with multiple transiting planet candidates identified by Kepler. We confirm four transiting planets in two multiple planet systems based on their TTVs and the constraints imposed by dynamical stability. An additional three candidates in these same systems are not confirmed as planets, but are likely to be validated as real planets once further observations and analyses are possible. If all were confirmed, these systems would be near 4:6:...

  16. Nickel-catalyzed proton-deuterium exchange (HDX) for linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural assignment of complex carbohydrates typically requires the analysis of at least three parameters: 1. composition; 2. linkage; and 3. substituents. These are often assigned on a small scale by gas chromatography/mass spectrometry (GC/MS). Linkage positions are determined by permethylat...

  17. Genome-Wide Linkage Analysis for Loci Affecting Pulse Pressure: The Family Blood Pressure Program

    National Research Council Canada - National Science Library

    Bielinski, Suzette J; Lynch, Amy I; Miller, Michael B; Weder, Alan; Cooper, Richard; Oberman, Albert; Chen, Yii-Der Ida; Turner, Stephen T; Fornage, Myriam; Province, Michael; Arnett, Donna K

    2005-01-01

    ... in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement...

  18. A Non-Parametric and Entropy Based Analysis of the Relationship between the VIX and S&P 500

    Directory of Open Access Journals (Sweden)

    Abhay K. Singh

    2013-10-01

    Full Text Available This paper features an analysis of the relationship between the S&P 500 Index and the VIX using daily data obtained from the CBOE website and SIRCA (The Securities Industry Research Centre of the Asia Pacific. We explore the relationship between the S&P 500 daily return series and a similar series for the VIX in terms of a long sample drawn from the CBOE from 1990 to mid 2011 and a set of returns from SIRCA’s TRTH datasets from March 2005 to-date. This shorter sample, which captures the behavior of the new VIX, introduced in 2003, is divided into four sub-samples which permit the exploration of the impact of the Global Financial Crisis. We apply a series of non-parametric based tests utilizing entropy based metrics. These suggest that the PDFs and CDFs of these two return distributions change shape in various subsample periods. The entropy and MI statistics suggest that the degree of uncertainty attached to these distributions changes through time and using the S&P 500 return as the dependent variable, that the amount of information obtained from the VIX changes with time and reaches a relative maximum in the most recent period from 2011 to 2012. The entropy based non-parametric tests of the equivalence of the two distributions and their symmetry all strongly reject their respective nulls. The results suggest that parametric techniques do not adequately capture the complexities displayed in the behavior of these series. This has practical implications for hedging utilizing derivatives written on the VIX.

  19. Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data

    Directory of Open Access Journals (Sweden)

    Smith Richard JH

    2005-02-01

    Full Text Available Abstract Background The identification of disease-associated genes using single nucleotide polymorphisms (SNPs has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. Results Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3 to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. Conclusions The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling

  20. The optimal design for hypothesis test and its application in genetic linkage analysis

    Institute of Scientific and Technical Information of China (English)

    XIE; Minyu(谢民育); LI; Zhaohai(李照海)

    2003-01-01

    This paper proposes a class of linear models with inequable variance, based on background in genetic linkage analysis, and considers the optimal design problem for the hypothesis test of the parameters in such models. To assess a design for the test, a frame of decision theory is established. Under this frame, an admissible minimax design is obtained. It is shown to be not only admissible and minimax in genetic linkage analysis, but best among a reasonable subclass of designs. The power of the test in genetic linkage analysis is substantially improved by using this optimal design.

  1. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.

  2. Nonparametric statistical inference

    CERN Document Server

    Gibbons, Jean Dickinson

    2010-01-01

    Overall, this remains a very fine book suitable for a graduate-level course in nonparametric statistics. I recommend it for all people interested in learning the basic ideas of nonparametric statistical inference.-Eugenia Stoimenova, Journal of Applied Statistics, June 2012… one of the best books available for a graduate (or advanced undergraduate) text for a theory course on nonparametric statistics. … a very well-written and organized book on nonparametric statistics, especially useful and recommended for teachers and graduate students.-Biometrics, 67, September 2011This excellently presente

  3. Analysis of Linkage Effects among Currency Networks Using REER Data

    Directory of Open Access Journals (Sweden)

    Haishu Qiao

    2015-01-01

    Full Text Available We modeled the currency networks through the use of REER (real effective exchange rate instead of a bilateral exchange rate in order to overcome the confusion in selecting base currencies. Based on the MST (minimum spanning tree approach and the rolling-window method, we constructed time-varying and correlation-based networks with which we investigate the linkage effects among different currencies. In particular, and as the source of empirical data, we chose the monthly REER data for a set of 61 major currencies during the period from 1994 to 2014. The study demonstrated that obvious linkage effects existed among currency networks and the euro (EUR was confirmed as the predominant world currency. Additionally, we used the rolling-window method to investigate the stability of linkage effects, doing so by calculating the mean correlations and mean distances as well as the normalized tree length and degrees of those currencies. The results showed that financial crises during the study period had a great effect on the currency network’s topology structure and led to more clustered currency networks. Our results suggested that it is more appropriate to estimate the linkage effects among currency networks through the use of REER data.

  4. ACCURACY ANALYSIS FOR PLANAR LINKAGE WITH MULTIPLE CLEAR-ANCES AT TURNING PAIRS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guojun; CHENG Qiang; SHAO Xinyu; LI Peigen

    2008-01-01

    Clearance at turning pair has a strong impact on the kinetic accuracy of linkage, but there is short of a generic model to analyze it so far. Clearance error, input error, and manufacturing tolerance of links are taken into consideration as the random variables synthetically. The kinematics and dynamics accuracy analysis models for planar linkages with multiple clearances at joints are built up as well. At last a typical planar linkage is selected for numerical illustration. These models stated in matrix resolve the relativity of output parameter errors of mechanism and therefore are of vital significance for the reliability analysis and synthesis of mechanism with clearances.

  5. GPU-accelerated nonparametric kinetic analysis of DCE-MRI data from glioblastoma patients treated with bevacizumab.

    Science.gov (United States)

    Hsu, Yu-Han H; Ferl, Gregory Z; Ng, Chee M

    2013-05-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is often used to examine vascular function in malignant tumors and noninvasively monitor drug efficacy of antivascular therapies in clinical studies. However, complex numerical methods used to derive tumor physiological properties from DCE-MRI images can be time-consuming and computationally challenging. Recent advancement of computing technology in graphics processing unit (GPU) makes it possible to build an energy-efficient and high-power parallel computing platform for solving complex numerical problems. This study develops the first reported fast GPU-based method for nonparametric kinetic analysis of DCE-MRI data using clinical scans of glioblastoma patients treated with bevacizumab (Avastin®). In the method, contrast agent concentration-time profiles in arterial blood and tumor tissue are smoothed using a robust kernel-based regression algorithm in order to remove artifacts due to patient motion and then deconvolved to produce the impulse response function (IRF). The area under the curve (AUC) and mean residence time (MRT) of the IRF are calculated using statistical moment analysis, and two tumor physiological properties that relate to vascular permeability, volume transfer constant between blood plasma and extravascular extracellular space (K(trans)) and fractional interstitial volume (ve) are estimated using the approximations AUC/MRT and AUC. The most significant feature in this method is the use of GPU-computing to analyze data from more than 60,000 voxels in each DCE-MRI image in parallel fashion. All analysis steps have been automated in a single program script that requires only blood and tumor data as the sole input. The GPU-accelerated method produces K(trans) and ve estimates that are comparable to results from previous studies but reduces computational time by more than 80-fold compared to a previously reported central processing unit-based nonparametric method. Furthermore, it is at

  6. Multivariate Stable Isotope Analysis to Determine Linkages between Benzocaine Seizures

    Science.gov (United States)

    Kemp, H. F.; Meier-Augenstein, W.; Collins, M.; Salouros, H.; Cunningham, A.; Harrison, M.

    2012-04-01

    In July 2010, a woman was jailed for nine years in the UK after the prosecution successfully argued that attempting to import a cutting agent was proof of involvement in a conspiracy to supply Cocaine. That landmark ruling provided law enforcement agencies with much greater scope to tackle those involved in this aspect of the drug trade, specifically targeting those importing the likes of benzocaine or lidocaine. Huge quantities of these compounds are imported into the UK and between May and August 2010, four shipments of Benzocaine amounting to more then 4 tons had been seized as part of Operation Kitley, a joint initiative between the UK Border Agency and the Serious Organised Crime Agency (SOCA). By diluting cocaine, traffickers can make it go a lot further for very little cost, leading to huge profits. In recent years, dealers have moved away from inert substances, like sugar and baby milk powder, in favour of active pharmaceutical ingredients (APIs), including anaesthetics like Benzocaine and Lidocaine. Both these mimic the numbing effect of cocaine, and resemble it closely in colour, texture and some chemical behaviours, making it easier to conceal the fact that the drug has been diluted. API cutting agents have helped traffickers to maintain steady supplies in the face of successful interdiction and even expand the market in the UK, particularly to young people aged from their mid teens to early twenties. From importation to street-level, the purity of the drug can be reduced up to a factor of 80 and street level cocaine can have a cocaine content as low as 1%. In view of the increasing use of Benzocaine as cutting agent for Cocaine, a study was carried out to investigate if 2H, 13C, 15N and 18O stable isotope signatures could be used in conjunction with multivariate chemometric data analysis to determine potential linkage between benzocaine exhibits seized from different locations or individuals to assist with investigation and prosecution of drug

  7. Non-parametric analysis of infrared spectra for recognition of glass and glass ceramic fragments in recycling plants.

    Science.gov (United States)

    Farcomeni, Alessio; Serranti, Silvia; Bonifazi, Giuseppe

    2008-01-01

    Glass ceramic detection in glass recycling plants represents a still unsolved problem, as glass ceramic material looks like normal glass and is usually detected only by specialized personnel. The presence of glass-like contaminants inside waste glass products, resulting from both industrial and differentiated urban waste collection, increases process production costs and reduces final product quality. In this paper an innovative approach for glass ceramic recognition, based on the non-parametric analysis of infrared spectra, is proposed and investigated. The work was specifically addressed to the spectral classification of glass and glass ceramic fragments collected in an actual recycling plant from three different production lines: flat glass, colored container-glass and white container-glass. The analyses, carried out in the near and mid-infrared (NIR-MIR) spectral field (1280-4480 nm), show that glass ceramic and glass fragments can be recognized by applying a wavelet transform, with a small classification error. Moreover, a method for selecting only a small subset of relevant wavelength ratios is suggested, allowing the conduct of a fast recognition of the two classes of materials. The results show how the proposed approach can be utilized to develop a classification engine to be integrated inside a hardware and software sorting architecture for fast "on-line" ceramic glass recognition and separation.

  8. nparLD: An R Software Package for the Nonparametric Analysis of Longitudinal Data in Factorial Experiments

    Directory of Open Access Journals (Sweden)

    Kimihiro Noguchi

    2012-09-01

    Full Text Available Longitudinal data from factorial experiments frequently arise in various fields of study, ranging from medicine and biology to public policy and sociology. In most practical situations, the distribution of observed data is unknown and there may exist a number of atypical measurements and outliers. Hence, use of parametric and semi-parametric procedures that impose restrictive distributional assumptions on observed longitudinal samples becomes questionable. This, in turn, has led to a substantial demand for statistical procedures that enable us to accurately and reliably analyze longitudinal measurements in factorial experiments with minimal conditions on available data, and robust nonparametric methodology offering such a possibility becomes of particular practical importance. In this article, we introduce a new R package nparLD which provides statisticians and researchers from other disciplines an easy and user-friendly access to the most up-to-date robust rank-based methods for the analysis of longitudinal data in factorial settings. We illustrate the implemented procedures by case studies from dentistry, biology, and medicine.

  9. Zero- vs. one-dimensional, parametric vs. non-parametric, and confidence interval vs. hypothesis testing procedures in one-dimensional biomechanical trajectory analysis.

    Science.gov (United States)

    Pataky, Todd C; Vanrenterghem, Jos; Robinson, Mark A

    2015-05-01

    Biomechanical processes are often manifested as one-dimensional (1D) trajectories. It has been shown that 1D confidence intervals (CIs) are biased when based on 0D statistical procedures, and the non-parametric 1D bootstrap CI has emerged in the Biomechanics literature as a viable solution. The primary purpose of this paper was to clarify that, for 1D biomechanics datasets, the distinction between 0D and 1D methods is much more important than the distinction between parametric and non-parametric procedures. A secondary purpose was to demonstrate that a parametric equivalent to the 1D bootstrap exists in the form of a random field theory (RFT) correction for multiple comparisons. To emphasize these points we analyzed six datasets consisting of force and kinematic trajectories in one-sample, paired, two-sample and regression designs. Results showed, first, that the 1D bootstrap and other 1D non-parametric CIs were qualitatively identical to RFT CIs, and all were very different from 0D CIs. Second, 1D parametric and 1D non-parametric hypothesis testing results were qualitatively identical for all six datasets. Last, we highlight the limitations of 1D CIs by demonstrating that they are complex, design-dependent, and thus non-generalizable. These results suggest that (i) analyses of 1D data based on 0D models of randomness are generally biased unless one explicitly identifies 0D variables before the experiment, and (ii) parametric and non-parametric 1D hypothesis testing provide an unambiguous framework for analysis when one׳s hypothesis explicitly or implicitly pertains to whole 1D trajectories.

  10. A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait

    Science.gov (United States)

    Zhang, Yanli; Liao, Zetao; Wei, Qiujing; Pan, Yunfeng; Wang, Xinwei; Cao, Shuangyan; Guo, Zishi; Wu, Yuqiong; Rong, Ju; Jin, Ou; Xu, Manlong; Gu, Jieruo

    2016-01-01

    Objectives To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner. Patients and Methods AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN. Result Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis. Conclusion Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients. PMID:27973620

  11. Meta-analysis of genome-wide linkage studies across autoimmune diseases

    Science.gov (United States)

    Forabosco, Paola; Bouzigon, Emmanuelle; Ng, Mandy Y; Hermanowski, Jane; Fisher, Sheila A; Criswell, Lindsey A; Lewis, Cathryn M

    2009-01-01

    Autoimmune diseases are chronic disorders initiated by a loss of immunologic tolerance to self-antigens. They cluster within families, and patients may be diagnosed with more than one disease, suggesting pleiotropic genes are involved in the aetiology of different diseases. To identify potential loci, which confer susceptibility to autoimmunity independent of disease phenotype, we pooled results from genome-wide linkage studies, using the genome scan meta-analysis method (GSMA). The meta-analysis included 42 independent studies for 11 autoimmune diseases, using 7350 families with 18 291 affected individuals. In addition to the HLA region, which showed highly significant genome-wide evidence for linkage, we obtained suggestive evidence for linkage on chromosome 16, with peak evidence at 10.0–19.8 Mb. This region may harbour a pleiotropic gene (or genes) conferring risk for several diseases, although no such gene has been identified through association studies. We did not identify evidence for linkage at several genes known to confer increased risk to different autoimmune diseases (PTPN22, CTLA4), even in subgroups of diseases consistently found to be associated with these genes. The relative risks conferred by variants in these genes are modest (<1.5 in most cases), and even a large study like this meta-analysis lacks power to detect linkage. This study illustrates the concept that linkage and association studies have power to identify very different types of disease-predisposing variants. PMID:18781189

  12. The Efficiency Change of Italian Public Universities in the New Millennium: A Non-Parametric Analysis

    Science.gov (United States)

    Guccio, Calogero; Martorana, Marco Ferdinando; Mazza, Isidoro

    2017-01-01

    The paper assesses the evolution of efficiency of Italian public universities for the period 2000-2010. It aims at investigating whether their levels of efficiency showed signs of convergence, and if the well-known disparity between northern and southern regions decreased. For this purpose, we use a refinement of data envelopment analysis, namely…

  13. The effects of selection on linkage analysis for quantitative traits.

    Science.gov (United States)

    Mackinnon, M J; Georges, M A

    1992-12-01

    The effects of within-sample selection on the outcome of analyses detecting linkage between genetic markers and quantitative traits were studied. It was found that selection by truncation for the trait of interest significantly reduces the differences between marker genotype means thus reducing the power to detect linked quantitative trait loci (QTL). The size of this reduction is a function of proportion selected, the magnitude of the QTL effect, recombination rate between the marker locus and the QTL, and the allele frequency of the QTL. Proportion selected was the most influential of these factors on bias, e.g., for an allele substitution effect of one standard deviation unit, selecting the top 80%, 50% or 20% of the population required 2, 6 or 24 times the number of progeny, respectively, to offset the loss of power caused by this selection. The effect on power was approximately linear with respect to the size of gene effect, almost invariant to recombination rate, and a complex function of QTL allele frequency. It was concluded that experimental samples from animal populations which have been subjected to even minor amounts of selection will be inefficient in yielding information on linkage between markers and loci influencing the quantitative trait under selection.

  14. Non-parametric group-level statistics for source-resolved ERP analysis.

    Science.gov (United States)

    Lee, Clement; Miyakoshi, Makoto; Delorme, Arnaud; Cauwenberghs, Gert; Makeig, Scott

    2015-01-01

    We have developed a new statistical framework for group-level event-related potential (ERP) analysis in EEGLAB. The framework calculates the variance of scalp channel signals accounted for by the activity of homogeneous clusters of sources found by independent component analysis (ICA). When ICA data decomposition is performed on each subject's data separately, functionally equivalent ICs can be grouped into EEGLAB clusters. Here, we report a new addition (statPvaf) to the EEGLAB plug-in std_envtopo to enable inferential statistics on main effects and interactions in event related potentials (ERPs) of independent component (IC) processes at the group level. We demonstrate the use of the updated plug-in on simulated and actual EEG data.

  15. Nonparametric Bayesian Inference for Mean Residual Life Functions in Survival Analysis

    OpenAIRE

    Poynor, Valerie; Kottas, Athanasios

    2014-01-01

    Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life function which provides the expected remaining lifetime given that a subject has survived (i.e., is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the mean residual life function characterizes the sur...

  16. Transit Timing Observations from Kepler: II. Confirmation of Two Multiplanet Systems via a Non-parametric Correlation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Eric B.; /Florida U.; Fabrycky, Daniel C.; /Lick Observ.; Steffen, Jason H.; /Fermilab; Carter, Joshua A.; /Harvard-Smithsonian Ctr. Astrophys.; Fressin, Francois; /Harvard-Smithsonian Ctr. Astrophys.; Holman, Matthew J.; /Harvard-Smithsonian Ctr. Astrophys.; Lissauer, Jack J.; /NASA, Ames; Moorhead, Althea V.; /Florida U.; Morehead, Robert C.; /Florida U.; Ragozzine, Darin; /Harvard-Smithsonian Ctr. Astrophys.; Rowe, Jason F.; /NASA, Ames /SETI Inst., Mtn. View /San Diego State U., Astron. Dept.

    2012-01-01

    We present a new method for confirming transiting planets based on the combination of transit timing variations (TTVs) and dynamical stability. Correlated TTVs provide evidence that the pair of bodies are in the same physical system. Orbital stability provides upper limits for the masses of the transiting companions that are in the planetary regime. This paper describes a non-parametric technique for quantifying the statistical significance of TTVs based on the correlation of two TTV data sets. We apply this method to an analysis of the transit timing variations of two stars with multiple transiting planet candidates identified by Kepler. We confirm four transiting planets in two multiple planet systems based on their TTVs and the constraints imposed by dynamical stability. An additional three candidates in these same systems are not confirmed as planets, but are likely to be validated as real planets once further observations and analyses are possible. If all were confirmed, these systems would be near 4:6:9 and 2:4:6:9 period commensurabilities. Our results demonstrate that TTVs provide a powerful tool for confirming transiting planets, including low-mass planets and planets around faint stars for which Doppler follow-up is not practical with existing facilities. Continued Kepler observations will dramatically improve the constraints on the planet masses and orbits and provide sensitivity for detecting additional non-transiting planets. If Kepler observations were extended to eight years, then a similar analysis could likely confirm systems with multiple closely spaced, small transiting planets in or near the habitable zone of solar-type stars.

  17. Quantal Response: Nonparametric Modeling

    Science.gov (United States)

    2017-01-01

    spline N−spline Fig. 3 Logistic regression 7 Approved for public release; distribution is unlimited. 5. Nonparametric QR Models Nonparametric linear ...stimulus and probability of response. The Generalized Linear Model approach does not make use of the limit distribution but allows arbitrary functional...7. Conclusions and Recommendations 18 8. References 19 Appendix A. The Linear Model 21 Appendix B. The Generalized Linear Model 33 Appendix C. B

  18. A Parcellation Based Nonparametric Algorithm for Independent Component Analysis with Application to fMRI Data

    Directory of Open Access Journals (Sweden)

    Shanshan eLi

    2016-01-01

    Full Text Available Independent Component analysis (ICA is a widely used technique for separating signals that have been mixed together. In this manuscript, we propose a novel ICA algorithm using density estimation and maximum likelihood, where the densities of the signals are estimated via p-spline based histogram smoothing and the mixing matrix is simultaneously estimated using an optimization algorithm. The algorithm is exceedingly simple, easy to implement and blind to the underlying distributions of the source signals. To relax the identically distributed assumption in the density function, a modified algorithm is proposed to allow for different density functions on different regions. The performance of the proposed algorithm is evaluated in different simulation settings. For illustration, the algorithm is applied to a research investigation with a large collection of resting state fMRI datasets. The results show that the algorithm successfully recovers the established brain networks.

  19. Adaptive Kernel Canonical Correlation Analysis Algorithms for Nonparametric Identification of Wiener and Hammerstein Systems

    Directory of Open Access Journals (Sweden)

    Ignacio Santamaría

    2008-04-01

    Full Text Available This paper treats the identification of nonlinear systems that consist of a cascade of a linear channel and a nonlinearity, such as the well-known Wiener and Hammerstein systems. In particular, we follow a supervised identification approach that simultaneously identifies both parts of the nonlinear system. Given the correct restrictions on the identification problem, we show how kernel canonical correlation analysis (KCCA emerges as the logical solution to this problem. We then extend the proposed identification algorithm to an adaptive version allowing to deal with time-varying systems. In order to avoid overfitting problems, we discuss and compare three possible regularization techniques for both the batch and the adaptive versions of the proposed algorithm. Simulations are included to demonstrate the effectiveness of the presented algorithm.

  20. Introduction to nonparametric statistics for the biological sciences using R

    CERN Document Server

    MacFarland, Thomas W

    2016-01-01

    This book contains a rich set of tools for nonparametric analyses, and the purpose of this supplemental text is to provide guidance to students and professional researchers on how R is used for nonparametric data analysis in the biological sciences: To introduce when nonparametric approaches to data analysis are appropriate To introduce the leading nonparametric tests commonly used in biostatistics and how R is used to generate appropriate statistics for each test To introduce common figures typically associated with nonparametric data analysis and how R is used to generate appropriate figures in support of each data set The book focuses on how R is used to distinguish between data that could be classified as nonparametric as opposed to data that could be classified as parametric, with both approaches to data classification covered extensively. Following an introductory lesson on nonparametric statistics for the biological sciences, the book is organized into eight self-contained lessons on various analyses a...

  1. Genome-wide linkage and copy number variation analysis reveals 710 kb duplication on chromosome 1p31.3 responsible for autosomal dominant omphalocele

    Science.gov (United States)

    Radhakrishna, Uppala; Nath, Swapan K; McElreavey, Ken; Ratnamala, Uppala; Sun, Celi; Maiti, Amit K; Gagnebin, Maryline; Béna, Frédérique; Newkirk, Heather L; Sharp, Andrew J; Everman, David B; Murray, Jeffrey C; Schwartz, Charles E; Antonarakis, Stylianos E; Butler, Merlin G

    2017-01-01

    Background Omphalocele is a congenital birth defect characterised by the presence of internal organs located outside of the ventral abdominal wall. The purpose of this study was to identify the underlying genetic mechanisms of a large autosomal dominant Caucasian family with omphalocele. Methods and findings A genetic linkage study was conducted in a large family with an autosomal dominant transmission of an omphalocele using a genome-wide single nucleotide polymorphism (SNP) array. The analysis revealed significant evidence of linkage (non-parametric NPL = 6.93, p=0.0001; parametric logarithm of odds (LOD) = 2.70 under a fully penetrant dominant model) at chromosome band 1p31.3. Haplotype analysis narrowed the locus to a 2.74 Mb region between markers rs2886770 (63014807 bp) and rs1343981 (65757349 bp). Molecular characterisation of this interval using array comparative genomic hybridisation followed by quantitative microsphere hybridisation analysis revealed a 710 kb duplication located at 63.5–64.2 Mb. All affected individuals who had an omphalocele and shared the haplotype were positive for this duplicated region, while the duplication was absent from all normal individuals of this family. Multipoint linkage analysis using the duplication as a marker yielded a maximum LOD score of 3.2 at 1p31.3 under a dominant model. The 710 kb duplication at 1p31.3 band contains seven known genes including FOXD3, ALG6, ITGB3BP, KIAA1799, DLEU2L, PGM1, and the proximal portion of ROR1. Importantly, this duplication is absent from the database of genomic variants. Conclusions The present study suggests that development of an omphalocele in this family is controlled by overexpression of one or more genes in the duplicated region. To the authors’ knowledge, this is the first reported association of an inherited omphalocele condition with a chromosomal rearrangement. PMID:22499347

  2. A non-parametric meta-analysis approach for combining independent microarray datasets: application using two microarray datasets pertaining to chronic allograft nephropathy

    Directory of Open Access Journals (Sweden)

    Archer Kellie J

    2008-02-01

    Full Text Available Abstract Background With the popularity of DNA microarray technology, multiple groups of researchers have studied the gene expression of similar biological conditions. Different methods have been developed to integrate the results from various microarray studies, though most of them rely on distributional assumptions, such as the t-statistic based, mixed-effects model, or Bayesian model methods. However, often the sample size for each individual microarray experiment is small. Therefore, in this paper we present a non-parametric meta-analysis approach for combining data from independent microarray studies, and illustrate its application on two independent Affymetrix GeneChip studies that compared the gene expression of biopsies from kidney transplant recipients with chronic allograft nephropathy (CAN to those with normal functioning allograft. Results The simulation study comparing the non-parametric meta-analysis approach to a commonly used t-statistic based approach shows that the non-parametric approach has better sensitivity and specificity. For the application on the two CAN studies, we identified 309 distinct genes that expressed differently in CAN. By applying Fisher's exact test to identify enriched KEGG pathways among those genes called differentially expressed, we found 6 KEGG pathways to be over-represented among the identified genes. We used the expression measurements of the identified genes as predictors to predict the class labels for 6 additional biopsy samples, and the predicted results all conformed to their pathologist diagnosed class labels. Conclusion We present a new approach for combining data from multiple independent microarray studies. This approach is non-parametric and does not rely on any distributional assumptions. The rationale behind the approach is logically intuitive and can be easily understood by researchers not having advanced training in statistics. Some of the identified genes and pathways have been

  3. A non-parametric meta-analysis approach for combining independent microarray datasets: application using two microarray datasets pertaining to chronic allograft nephropathy.

    Science.gov (United States)

    Kong, Xiangrong; Mas, Valeria; Archer, Kellie J

    2008-02-26

    With the popularity of DNA microarray technology, multiple groups of researchers have studied the gene expression of similar biological conditions. Different methods have been developed to integrate the results from various microarray studies, though most of them rely on distributional assumptions, such as the t-statistic based, mixed-effects model, or Bayesian model methods. However, often the sample size for each individual microarray experiment is small. Therefore, in this paper we present a non-parametric meta-analysis approach for combining data from independent microarray studies, and illustrate its application on two independent Affymetrix GeneChip studies that compared the gene expression of biopsies from kidney transplant recipients with chronic allograft nephropathy (CAN) to those with normal functioning allograft. The simulation study comparing the non-parametric meta-analysis approach to a commonly used t-statistic based approach shows that the non-parametric approach has better sensitivity and specificity. For the application on the two CAN studies, we identified 309 distinct genes that expressed differently in CAN. By applying Fisher's exact test to identify enriched KEGG pathways among those genes called differentially expressed, we found 6 KEGG pathways to be over-represented among the identified genes. We used the expression measurements of the identified genes as predictors to predict the class labels for 6 additional biopsy samples, and the predicted results all conformed to their pathologist diagnosed class labels. We present a new approach for combining data from multiple independent microarray studies. This approach is non-parametric and does not rely on any distributional assumptions. The rationale behind the approach is logically intuitive and can be easily understood by researchers not having advanced training in statistics. Some of the identified genes and pathways have been reported to be relevant to renal diseases. Further study on the

  4. Viral Genetic Linkage Analysis in the Presence of Missing Data.

    Directory of Open Access Journals (Sweden)

    Shelley H Liu

    Full Text Available Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations.

  5. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG families

    Directory of Open Access Journals (Sweden)

    Bailey-Wilson Joan E

    2012-06-01

    Full Text Available Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG. Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD of 1.28, and an allele-sharing lod score (LOD of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM. For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission

  6. Linkage analysis of quantitative trait loci in the presence of heterogeneity.

    Science.gov (United States)

    Ekstrøm, Claus Thorn; Dalgaard, Peter

    2003-01-01

    Variance component modeling for linkage analysis of quantitative traits is a powerful tool for detecting and locating genes affecting a trait of interest, but the presence of genetic heterogeneity will decrease the power of a linkage study and may even give biased estimates of the location of the quantitative trait loci. Many complex diseases are believed to be influenced by multiple genes and therefore genetic heterogeneity is likely to be present for many real applications of linkage analysis. We consider a mixture of multivariate normals to model locus heterogeneity by allowing only a proportion of the sampled pedigrees to segregate trait-influencing allele(s) at a specific locus. However, for mixtures of normals the classical asymptotic distribution theory of the maximum likelihood estimates does not hold, so tests of linkage and/or heterogeneity are evaluated using resampling methods. It is shown that allowing for genetic heterogeneity leads to an increase in power to detect linkage. This increase is more prominent when the genetic effect of the locus is small or when the percentage of pedigrees not segregating trait-influencing allele(s) at the locus is high.

  7. Genome-wide family-based linkage analysis of exome chip variants and cardiometabolic risk.

    Science.gov (United States)

    Hellwege, Jacklyn N; Palmer, Nicholette D; Raffield, Laura M; Ng, Maggie C Y; Hawkins, Gregory A; Long, Jirong; Lorenzo, Carlos; Norris, Jill M; Ida Chen, Y-D; Speliotes, Elizabeth K; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

    2014-05-01

    Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 Hispanic (n = 1,414) families in the Insulin Resistance Atherosclerosis Family Study (IRASFS) using Illumina HumanExome Beadchips. A total of 92,157 variants in African Americans (34%) and 81,559 (31%) in Hispanics were polymorphic and tested using two-point linkage and association analyses with 37 cardiometabolic phenotypes. In African Americans 77 LOD scores greater than 3 were observed. The highest LOD score was 4.91 with the APOE SNP rs7412 (MAF = 0.13) with plasma apolipoprotein B (ApoB). This SNP was associated with ApoB (P-value = 4 × 10(-19)) and accounted for 16.2% of the variance in African Americans. In Hispanic families, 104 LOD scores were greater than 3. The strongest evidence of linkage (LOD = 4.29) was with rs5882 (MAF = 0.46) in CETP with HDL. CETP variants were strongly associated with HDL (0.00049 evidence of strong linkage in this genome wide survey of primarily coding variants was uncommon. Loci with strong evidence of linkage was characterized by large contributions to the variance, and, in these cases, are common variants. Less compelling evidence of linkage and association was observed with additional loci that may require larger family sets to confirm. © 2014 WILEY PERIODICALS, INC.

  8. Transit Timing Observations From Kepler: Ii. Confirmation of Two Multiplanet Systems via a Non-Parametric Correlation Analysis

    OpenAIRE

    Ford, Eric B.; Fabrycky, Daniel C.; Steffen, Jason H.; Carter, Joshua A.; Fressin, Francois; Holman, Matthew Jon; Lissauer, Jack J.; Moorhead, Althea V.; Morehead, Robert C.; Ragozzine, Darin; Rowe, Jason F.; Welsh, William F.; Allen, Christopher; Batalha, Natalie M.; Borucki, William J.

    2012-01-01

    We present a new method for confirming transiting planets based on the combination of transit timingn variations (TTVs) and dynamical stability. Correlated TTVs provide evidence that the pair of bodies are in the same physical system. Orbital stability provides upper limits for the masses of the transiting companions that are in the planetary regime. This paper describes a non-parametric technique for quantifying the statistical significance of TTVs based on the correlation of two TTV data se...

  9. Nonparametric statistical methods

    CERN Document Server

    Hollander, Myles; Chicken, Eric

    2013-01-01

    Praise for the Second Edition"This book should be an essential part of the personal library of every practicing statistician."-Technometrics  Thoroughly revised and updated, the new edition of Nonparametric Statistical Methods includes additional modern topics and procedures, more practical data sets, and new problems from real-life situations. The book continues to emphasize the importance of nonparametric methods as a significant branch of modern statistics and equips readers with the conceptual and technical skills necessary to select and apply the appropriate procedures for any given sit

  10. Prospective linkages between peer victimization and externalizing problems in children: a meta-analysis.

    Science.gov (United States)

    Reijntjes, Albert; Kamphuis, Jan H; Prinzie, Peter; Boelen, Paul A; van der Schoot, Menno; Telch, Michael J

    2011-01-01

    Previous meta-analytic research has shown both concurrent and prospective linkages between peer victimization and internalizing problems in youth. However, the linkages between peer victimization and externalizing problems over time have not been systematically examined, and it is therefore unknown if externalizing problems are antecedents of victimization, consequences of victimization, both, or neither. This study provides a meta-analysis of 14 longitudinal studies examining prospective linkages between peer victimization and externalizing problems (n = 7,821). Two prospective paths were examined: the extent to which peer victimization at baseline predicts future residualized changes in externalizing problems, as well as the extent to which externalizing problems at baseline predict future residualized changes in peer victimization. Results revealed significant associations between peer victimization and subsequent residualized changes in externalizing problems, as well as significant associations between externalizing problems and subsequent residualized changes in peer victimization. Hence, externalizing problems function as both antecedents and consequences of peer victimization. © 2010 Wiley-Liss, Inc.

  11. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  12. VT Wildlife Linkage Habitat

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The Wildlife Linkage Habitat Analysis uses landscape scale data to identify or predict the location of potentially significant wildlife linkage...

  13. Genome-wide Linkage Disequilibrium Linkage Analysis (LDLA) of Body Fat Traits in an F2 Porcine Model for Human Obesity

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Cirera Salicio, Susanna;

    , body composition was determined at about two months of age (64 ± 11 days) via dual-energy xray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined LDLA approach was used to perform genomewide linkage and association analysis for body fat traits...

  14. SwiftLink: parallel MCMC linkage analysis using multicore CPU and GPU.

    Science.gov (United States)

    Medlar, Alan; Głowacka, Dorota; Stanescu, Horia; Bryson, Kevin; Kleta, Robert

    2013-02-15

    Linkage analysis remains an important tool in elucidating the genetic component of disease and has become even more important with the advent of whole exome sequencing, enabling the user to focus on only those genomic regions co-segregating with Mendelian traits. Unfortunately, methods to perform multipoint linkage analysis scale poorly with either the number of markers or with the size of the pedigree. Large pedigrees with many markers can only be evaluated with Markov chain Monte Carlo (MCMC) methods that are slow to converge and, as no attempts have been made to exploit parallelism, massively underuse available processing power. Here, we describe SWIFTLINK, a novel application that performs MCMC linkage analysis by spreading the computational burden between multiple processor cores and a graphics processing unit (GPU) simultaneously. SWIFTLINK was designed around the concept of explicitly matching the characteristics of an algorithm with the underlying computer architecture to maximize performance. We implement our approach using existing Gibbs samplers redesigned for parallel hardware. We applied SWIFTLINK to a real-world dataset, performing parametric multipoint linkage analysis on a highly consanguineous pedigree with EAST syndrome, containing 28 members, where a subset of individuals were genotyped with single nucleotide polymorphisms (SNPs). In our experiments with a four core CPU and GPU, SWIFTLINK achieves a 8.5× speed-up over the single-threaded version and a 109× speed-up over the popular linkage analysis program SIMWALK. SWIFTLINK is available at https://github.com/ajm/swiftlink. All source code is licensed under GPLv3.

  15. Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease.

    Science.gov (United States)

    Silverman, Edwin K; Palmer, Lyle J; Mosley, Jonathan D; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-05-01

    Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV(1), FVC, and FEV(1)/FVC. In the initial genomewide scan, significant evidence for linkage to FEV(1)/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV(1)/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV(1) in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV(1) (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV(1)/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis.

  16. CATDAT : A Program for Parametric and Nonparametric Categorical Data Analysis : User's Manual Version 1.0, 1998-1999 Progress Report.

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, James T.

    1999-12-01

    Natural resource professionals are increasingly required to develop rigorous statistical models that relate environmental data to categorical responses data. Recent advances in the statistical and computing sciences have led to the development of sophisticated methods for parametric and nonparametric analysis of data with categorical responses. The statistical software package CATDAT was designed to make some of these relatively new and powerful techniques available to scientists. The CATDAT statistical package includes 4 analytical techniques: generalized logit modeling; binary classification tree; extended K-nearest neighbor classification; and modular neural network.

  17. Statistical analysis of water-quality data containing multiple detection limits II: S-language software for nonparametric distribution modeling and hypothesis testing

    Science.gov (United States)

    Lee, L.; Helsel, D.

    2007-01-01

    Analysis of low concentrations of trace contaminants in environmental media often results in left-censored data that are below some limit of analytical precision. Interpretation of values becomes complicated when there are multiple detection limits in the data-perhaps as a result of changing analytical precision over time. Parametric and semi-parametric methods, such as maximum likelihood estimation and robust regression on order statistics, can be employed to model distributions of multiply censored data and provide estimates of summary statistics. However, these methods are based on assumptions about the underlying distribution of data. Nonparametric methods provide an alternative that does not require such assumptions. A standard nonparametric method for estimating summary statistics of multiply-censored data is the Kaplan-Meier (K-M) method. This method has seen widespread usage in the medical sciences within a general framework termed "survival analysis" where it is employed with right-censored time-to-failure data. However, K-M methods are equally valid for the left-censored data common in the geosciences. Our S-language software provides an analytical framework based on K-M methods that is tailored to the needs of the earth and environmental sciences community. This includes routines for the generation of empirical cumulative distribution functions, prediction or exceedance probabilities, and related confidence limits computation. Additionally, our software contains K-M-based routines for nonparametric hypothesis testing among an unlimited number of grouping variables. A primary characteristic of K-M methods is that they do not perform extrapolation and interpolation. Thus, these routines cannot be used to model statistics beyond the observed data range or when linear interpolation is desired. For such applications, the aforementioned parametric and semi-parametric methods must be used.

  18. Linkage analysis by two-dimensional DNA typing

    NARCIS (Netherlands)

    te Meerman, G J; Mullaart, E; van der Meulen, M A; den Daas, J H; Morolli, B; Uitterlinden, A G; Vijg, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core pro

  19. Multipoint linkage analysis in X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Kruse, T A; Thomsen, A

    1991-01-01

    In order to localize the gene for the X-linked form of Alport syndrome (ATS) more precisely, we performed restriction fragment length polymorphism analysis with nine different X-chromosomal DNA markers in 107 members of twelve Danish families segregating for classic ATS or progressive hereditary ...

  20. A high-density screen for linkage in multiple sclerosis.

    Science.gov (United States)

    Sawcer, Stephen; Ban, Maria; Maranian, Mel; Yeo, Tai Wai; Compston, Alastair; Kirby, Andrew; Daly, Mark J; De Jager, Philip L; Walsh, Emily; Lander, Eric S; Rioux, John D; Hafler, David A; Ivinson, Adrian; Rimmler, Jacqueline; Gregory, Simon G; Schmidt, Silke; Pericak-Vance, Margaret A; Akesson, Eva; Hillert, Jan; Datta, Pameli; Oturai, Annette; Ryder, Lars P; Harbo, Hanne F; Spurkland, Anne; Myhr, Kjell-Morten; Laaksonen, Mikko; Booth, David; Heard, Robert; Stewart, Graeme; Lincoln, Robin; Barcellos, Lisa F; Hauser, Stephen L; Oksenberg, Jorge R; Kenealy, Shannon J; Haines, Jonathan L

    2005-09-01

    To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

  1. 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.

  2. 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

  3. Bivariate linkage analysis of the insulin resistance syndrome phenotypes on chromosome 7q.

    Science.gov (United States)

    Lehman, Donna M; Arya, Rector; Blangero, John; Almasy, Laura; Puppala, Sobha; Dyer, Thomas D; Leach, Robin J; O'Connell, Peter; Stern, Michael P; Duggirala, Ravindranath

    2005-04-01

    Metabolic abnormalities of the insulin resistance syndrome (IRS) have been shown to aggregate in families and to exhibit trait-pair correlations, suggesting a common genetic component. A broad region on chromosome 7q has been implicated in several studies to contain loci that cosegregate with IRS-related traits. However, it is not clear whether such loci have any common genetic (pleiotropic) influences on the correlated traits. Also, it is not clear whether the chromosomal regions contain more than one locus influencing the IRS-related phenotypes. In this study we present evidence for linkage of five IRS-related traits [body mass index (BMI), waist circumference (WC), In split proinsulin (LSPI), In triglycerides (LTG), and high-density lipoprotein cholesterol (HDLC)] to a region at 7q11.23. Subsequently, to gain further insight into the genetic component(s) mapping to this region, we explored whether linkage of these traits is due to pleiotropic effects using a bivariate linkage analytical technique, which has been shown to localize susceptibility regions with precision. Four hundred forty individuals from 27 Mexican American families living in Texas were genotyped for 19 highly polymorphic markers on chromosome 7. Multipoint variance component linkage analysis was used to identify genetic location(s) influencing IRS-related traits of obesity (BMI and WC), dyslipidemia (LTG and HDLC), and insulin levels (LSPI); the analysis identified a broad chromosomal region spanning approximately 24 cM. To gain more precision in localization, we used a bivariate linkage approach for each trait pair. These analyses suggest localization of most of these bivariate traits to an approximately 6-cM region near marker D7S653 [7q11.23, 103-109 cM; a maximum bivariate LOD of 4.51 was found for the trait pair HDLC and LSPI (the LODeq score is 3.94)]. We observed evidence of pleiotropic effects in this region on obesity and insulin-related trait pairs.

  4. Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice.

    Directory of Open Access Journals (Sweden)

    Prashant Vikram

    Full Text Available Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM to estimate the significance of pleiotropy effects. Results indicated towards possible linkages between the drought grain yield QTLs with co-locating flowering and/or plant height QTLs. Linkages of days to flowering and plant height were eliminated through a marker-assisted breeding approach. Drought grain yield QTLs also showed interaction effects with flowering QTLs. Drought responsiveness of the flowering locus on chromosome 3 (qDTY3.2 has been revealed through allelic analysis. Considering linkage and interaction effects associated with drought QTLs, a comprehensive marker-assisted breeding strategy was followed to develop rice genotypes with improved grain yield under drought stress.

  5. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred

    Energy Technology Data Exchange (ETDEWEB)

    Charles, S.J.; Moore, A.T.; Barton, D.E.; Yates, J.R.W. (Addenbrooke' s Hospital, Cambridge (United Kingdom)); Green, J.S. (Memorial Univ. of Newfoundland, St. John' s (Canada))

    1993-04-01

    Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Z[sub max] = 21.96 at [theta] = 0.01, confidence interval (CI) 0.0005--0.05) and linkage to DXS85 (782; Z[sub max] = 17.60 at [theta] = 0.07, CI = 0.03--0.13) and DXS237 (GMGX9; Z[sub max] = 15.20 at [theta] = 0.08, CI = 0.03--0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10[sup 10]:1 over other locations for the disease locus. 11 refs., 1 fig., 1 tab.

  6. QTL linkage analysis of connected populations using ancestral marker and pedigree information.

    Science.gov (United States)

    Bink, Marco C A M; Totir, L Radu; ter Braak, Cajo J F; Winkler, Christopher R; Boer, Martin P; Smith, Oscar S

    2012-04-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals' genotype probability without significantly increasing computational demand.

  7. Saturation of an intra-gene pool linkage map: towards a unified consensus linkage map for fine mapping and synteny analysis in common bean.

    Science.gov (United States)

    Galeano, Carlos H; Fernandez, Andrea C; Franco-Herrera, Natalia; Cichy, Karen A; McClean, Phillip E; Vanderleyden, Jos; Blair, Matthew W

    2011-01-01

    Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364 × BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364 × G19833 (DG) and BAT93 × JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning.

  8. Nonparametric Predictive Regression

    OpenAIRE

    Ioannis Kasparis; Elena Andreou; Phillips, Peter C.B.

    2012-01-01

    A unifying framework for inference is developed in predictive regressions where the predictor has unknown integration properties and may be stationary or nonstationary. Two easily implemented nonparametric F-tests are proposed. The test statistics are related to those of Kasparis and Phillips (2012) and are obtained by kernel regression. The limit distribution of these predictive tests holds for a wide range of predictors including stationary as well as non-stationary fractional and near unit...

  9. Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers

    Institute of Scientific and Technical Information of China (English)

    黄峻; 杨春梅; 马立隽; 单其俊; 许迪; 华子春; 曹克将

    2003-01-01

    Objective To explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees.Methods The microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession. Results The logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -∞, - (indicating that linkage is not supported in this mode), and -∞ respectively in autosomal dominant model (recombination fraction=0.000 respectively)and were -∞, -∞, -∞, -∞, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -∞, -, and 0 respectively in autosomal dominant model, and were -∞, -0.812, -∞, -∞, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -∞, -∞, -∞, and -∞ respectively in autosomal recessive model. Conclusions The LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150∶ 1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.

  10. Nonparametric factorial analysis of daily weigh-in-motion traffic: implications for the ozone "weekend effect" in Southern California

    Science.gov (United States)

    Gao, Oliver H.; Holmén, Britt A.; Niemeier, Debbie A.

    The Ozone Weekend Effect (OWE) has become increasingly more frequent and widespread in southern California since the mid-1970s. Although a number of hypotheses have been suggested to explain the effect, there remains uncertainty associated with the root factors contributing to elevated weekend ozone concentrations. Targeting the time window of the 1997 Southern California Ozone Study (SCOS97), this paper examines traffic activity data for 14 vehicle classes at 27 weigh-in-motion (WIM) stations in southern California. Nonparametric factorial analyses of light-duty vehicle (LDV) and heavy-duty truck (HDT) traffic volumes indicate significant differences in daily volumes by day of week and between the weekly patterns of daily LDV and HDT volumes. Across WIM stations, the daily LDV volume was highest on Friday and decreased by 10% on weekends compared to that on midweek days. In contrast, daily HDT volumes showed dramatic weekend drops of 53% on Saturday and 64% on Sunday. As a result, LDV to HDT ratios increased by 145% on weekends. Nonparametric tests also suggest that weekly traffic patterns varied significantly between WIM stations located close to (central) and far from (peripheral) the Los Angeles Metro area. Weekend increases in LDV/HDT ratios were more pronounced at central WIM sites due to greater weekend declines of HDT relative to LDV traffic. The implications of these weekly traffic patterns for the OWE in southern California were investigated by estimating daily WIM traffic on-road running exhaust emissions of total organic gas (TOG) and oxides of nitrogen (NO x) using EMFAC2002 emission factors. The results support the California Air Resource Board's (CARB's) NO x reduction hypothesis that greater weekend NO x reductions relative to volatile organic compound (VOC) emissions, in combinations with the VOC-limited ozone system, contribute to the OWE observed in the region. The results from this study can be used to develop weekend on-road mobile emission

  11. A Novel Linkage to Generalized Vitiligo on 4q13-q21 Identified in a Genomewide Linkage Analysis of Chinese Families

    OpenAIRE

    Chen, Jian-Jun; Huang, Wei; Gui, Jin-Ping; Yang, Sen; Zhou, Fu-Sheng; Xiong, Quan-Geng; Wu, Hong-Bo; Cui, Yong; Gao, Min; Li, Wei; Li, Jin-Xian; Yan, Kai-Lin; Yuan, Wen-tao; Xu, Shi-Jie; Liu, Jian-Jun

    2005-01-01

    Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far—on chromosomes 1p31, 6p21, 7q, 8p, and 17p13—in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at le...

  12. High-resolution mapping of the gene for cystinosis, using combined biochemical and linkage analysis.

    Science.gov (United States)

    Jean, G; Fuchshuber, A; Town, M M; Gribouval, O; Schneider, J A; Broyer, M; van't Hoff, W; Niaudet, P; Antignac, C

    1996-03-01

    Infantile nephropathic cystinosis is an autosomal recessive disorder characterized biochemically by an abnormally high intracellular content of free cystine in different organs and tissues due to a transport defect of cystine through the lysosomal membrane. Affected children present with the Fanconi syndrome and usually develop progressive renal failure within the 1st decade of life. Measurement of free cystine in purified polymorphonuclear leukocytes provides an accurate method for diagnosis and detection of heterozygous carriers. In order to localize the gene locus for cystinosis we performed linkage analysis in 18 cystinosis families. However, since 17 of these were simplex families, we decided to include the phenotypes of the heterozygous carriers previously determined by their leukocyte cystine content in the linkage analysis. This approach allowed us to obtain highly significant results, confirming the localization of the cystinosis gene locus recently mapped to the short arm of chromosome 17 by the Cystinosis Collaborative Research Group. Crucial recombination events allowed us to refine the interval of the cystinosis gene to a genetic distance of 1 cM. No evidence of genetic heterogeneity was found. Our results demonstrate that the use of the previously determined phenotypes of heterozygous carriers in linkage analysis provides a reliable method for the investigation of simplex families in autosomal recessive traits.

  13. Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy

    Institute of Scientific and Technical Information of China (English)

    MA Kai; LIU Ning-pu; YANG Xiu-fen; HAN Cui; ZHANG Ning; XU Jun; LIU Shou-bin; LU Hal; Torkel Snellingen; WANG Ning-li

    2009-01-01

    Background A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified.The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage nalysis.Methods Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography,fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months.Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted.Linkage analysis was performed for candidate genes or loci using microsatellite markers.Results Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD.The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUC Y2D, and AIPL1) and two genetic loci (4p15.2-16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.Conclusions The clinical findings of this Chinese family with CACD shared

  14. Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites.

    Science.gov (United States)

    Wang, Shuang; Huang, Song; Liu, Nianjun; Chen, Liang; Oh, Cheongeun; Zhao, Hongyu

    2005-12-30

    There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput genotyping technologies. In this study, we compared the performance of whole-genome scans using SNPs with microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were used in our analyses. We found that the results from the two scans had good overall concordance. One region on chromosome 2 and two regions on chromosome 7 showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both the SNP and microsatellite scans. The different results observed between the two scans may be explained by the difference observed in information content between the SNPs and the microsatellites.

  15. Ascertainment correction for Markov chain Monte Carlo segregation and linkage analysis of a quantitative trait.

    Science.gov (United States)

    Ma, Jianzhong; Amos, Christopher I; Warwick Daw, E

    2007-09-01

    Although extended pedigrees are often sampled through probands with extreme levels of a quantitative trait, Markov chain Monte Carlo (MCMC) methods for segregation and linkage analysis have not been able to perform ascertainment corrections. Further, the extent to which ascertainment of pedigrees leads to biases in the estimation of segregation and linkage parameters has not been previously studied for MCMC procedures. In this paper, we studied these issues with a Bayesian MCMC approach for joint segregation and linkage analysis, as implemented in the package Loki. We first simulated pedigrees ascertained through individuals with extreme values of a quantitative trait in spirit of the sequential sampling theory of Cannings and Thompson [Cannings and Thompson [1977] Clin. Genet. 12:208-212]. Using our simulated data, we detected no bias in estimates of the trait locus location. However, in addition to allele frequencies, when the ascertainment threshold was higher than or close to the true value of the highest genotypic mean, bias was also found in the estimation of this parameter. When there were multiple trait loci, this bias destroyed the additivity of the effects of the trait loci, and caused biases in the estimation all genotypic means when a purely additive model was used for analyzing the data. To account for pedigree ascertainment with sequential sampling, we developed a Bayesian ascertainment approach and implemented Metropolis-Hastings updates in the MCMC samplers used in Loki. Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci.

  16. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    Energy Technology Data Exchange (ETDEWEB)

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. (Sackler Faculty of Medicine, Ramat-Aviv (Israel)); Godel, V. (Ichilov Hospital, Tel-Aviv (Israel))

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  17. Multiatlas segmentation as nonparametric regression.

    Science.gov (United States)

    Awate, Suyash P; Whitaker, Ross T

    2014-09-01

    This paper proposes a novel theoretical framework to model and analyze the statistical characteristics of a wide range of segmentation methods that incorporate a database of label maps or atlases; such methods are termed as label fusion or multiatlas segmentation. We model these multiatlas segmentation problems as nonparametric regression problems in the high-dimensional space of image patches. We analyze the nonparametric estimator's convergence behavior that characterizes expected segmentation error as a function of the size of the multiatlas database. We show that this error has an analytic form involving several parameters that are fundamental to the specific segmentation problem (determined by the chosen anatomical structure, imaging modality, registration algorithm, and label-fusion algorithm). We describe how to estimate these parameters and show that several human anatomical structures exhibit the trends modeled analytically. We use these parameter estimates to optimize the regression estimator. We show that the expected error for large database sizes is well predicted by models learned on small databases. Thus, a few expert segmentations can help predict the database sizes required to keep the expected error below a specified tolerance level. Such cost-benefit analysis is crucial for deploying clinical multiatlas segmentation systems.

  18. Nonparametric correlation models for portfolio allocation

    DEFF Research Database (Denmark)

    Aslanidis, Nektarios; Casas, Isabel

    2013-01-01

    breaks in correlations. Only when correlations are constant does the parametric DCC model deliver the best outcome. The methodologies are illustrated by evaluating two interesting portfolios. The first portfolio consists of the equity sector SPDRs and the S&P 500, while the second one contains major......This article proposes time-varying nonparametric and semiparametric estimators of the conditional cross-correlation matrix in the context of portfolio allocation. Simulations results show that the nonparametric and semiparametric models are best in DGPs with substantial variability or structural...... currencies. Results show the nonparametric model generally dominates the others when evaluating in-sample. However, the semiparametric model is best for out-of-sample analysis....

  19. A Censored Nonparametric Software Reliability Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper analyses the effct of censoring on the estimation of failure rate, and presents a framework of a censored nonparametric software reliability model. The model is based on nonparametric testing of failure rate monotonically decreasing and weighted kernel failure rate estimation under the constraint of failure rate monotonically decreasing. Not only does the model have the advantages of little assumptions and weak constraints, but also the residual defects number of the software system can be estimated. The numerical experiment and real data analysis show that the model performs well with censored data.

  20. A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma

    DEFF Research Database (Denmark)

    Sun, Xiangqing; Vengoechea, Jaime; Elston, Robert

    2012-01-01

    We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.......We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma....

  1. 二维PCA非参数子空间分析的人脸识别算法%Face Recognition Algorithm of 2DPCA Nonparametric Subspace Analysis

    Institute of Scientific and Technical Information of China (English)

    王美; 梁久祯

    2011-01-01

    This paper proposes a novel face recognition algorithm of 2D Nonparametric Subspace Analysis(2DNSA) based on 2D Principal Componet Analysis(2DPCA) subspace. The original face matrices are performed to have feature dimension reduction, and the reduced feature matrices are used as a new training set, which can be conducted by 2D non-parametric subspace analysis. This method not only can reduce feature dimensions by 2DPCA, but also consider the impact of boundary samples for classification by taking full advantage of classification capacity of 2DNSA, which avoids the irrationality of using class centers to measure the distances of different classes. Experimental results on the two face databases(namely Yale and LARGE) show the improvements of the developed new algorithm over the traditional subspace methods such as (2D)2PCA, 2DPCA, (2D)2LDA, 2DLDA, 2DPCA+2DLDA, 2DNSA, etc.%提出一种结合二维PCA(2DPCA)的二维非参数子空间分析(2DNSA)人脸识别算法.利用2DPCA对原始图像矩阵进行特征降维,以降维后的特征为训练样本,进行二维非参数判别分析,并综合考虑类边界样本对分类的影响,采用2DNSA实现更合理的特征提取.基于Yale、LARGE人脸数据库的实验结果表明,与(2D)2pCA、2DPCA、(2D)2LDA、2DLDA、2DPCA+2DLDA、2DNSA算法相比,该算法性能更优.

  2. Genome-wide linkage analysis of malaria infection intensity and mild disease.

    Directory of Open Access Journals (Sweden)

    Christian Timmann

    2007-03-01

    Full Text Available Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (HbS, HbC, alpha(+ thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5, locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%. The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

  3. Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, D.R.; Sapp, P.; O`Regan, J.; McKenna-Yasek, D.; Schlumpf, K.S.; Haines, J.L.; Gusella, J.F.; Horvitz, H.R.; Brown, R.H. Jr. [Massachusetts Institute of Technology, Cambridge, MA (United States)

    1994-05-15

    Amyotrophic lateral sclerosis (ALS; Lou Gehrig`s Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS familes for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers reveal recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219. The only characterized gene within this segment was SOD-1, the structural gene for Cu, Zn SOD. 30 refs., 4 figs., 4 tabs.

  4. Nonparametric trend estimation in the presence of fractal noise: application to fMRI time-series analysis.

    Science.gov (United States)

    Afshinpour, Babak; Hossein-Zadeh, Gholam-Ali; Soltanian-Zadeh, Hamid

    2008-06-30

    Unknown low frequency fluctuations called "trend" are observed in noisy time-series measured for different applications. In some disciplines, they carry primary information while in other fields such as functional magnetic resonance imaging (fMRI) they carry nuisance effects. In all cases, however, it is necessary to estimate them accurately. In this paper, a method for estimating trend in the presence of fractal noise is proposed and applied to fMRI time-series. To this end, a partly linear model (PLM) is fitted to each time-series. The parametric and nonparametric parts of PLM are considered as contributions of hemodynamic response and trend, respectively. Using the whitening property of wavelet transform, the unknown components of the model are estimated in the wavelet domain. The results of the proposed method are compared to those of other parametric trend-removal approaches such as spline and polynomial models. It is shown that the proposed method improves activation detection and decreases variance of the estimated parameters relative to the other methods.

  5. Parametric and Nonparametric EEG Analysis for the Evaluation of EEG Activity in Young Children with Controlled Epilepsy

    Directory of Open Access Journals (Sweden)

    Vangelis Sakkalis

    2008-01-01

    Full Text Available There is an important evidence of differences in the EEG frequency spectrum of control subjects as compared to epileptic subjects. In particular, the study of children presents difficulties due to the early stages of brain development and the various forms of epilepsy indications. In this study, we consider children that developed epileptic crises in the past but without any other clinical, psychological, or visible neurophysiological findings. The aim of the paper is to develop reliable techniques for testing if such controlled epilepsy induces related spectral differences in the EEG. Spectral features extracted by using nonparametric, signal representation techniques (Fourier and wavelet transform and a parametric, signal modeling technique (ARMA are compared and their effect on the classification of the two groups is analyzed. The subjects performed two different tasks: a control (rest task and a relatively difficult math task. The results show that spectral features extracted by modeling the EEG signals recorded from individual channels by an ARMA model give a higher discrimination between the two subject groups for the control task, where classification scores of up to 100% were obtained with a linear discriminant classifier.

  6. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22.

    Science.gov (United States)

    Zhong, Wei; Cui, Bin; Zhang, Yizhi; Jiang, Haisong; Wei, Shengcai; Bu, Lei; Zhao, Guoping; Hu, Landian; Kong, Xiangyin

    2003-01-01

    Ichthyosis vulgaris (IV) is an inherited scaling skin disorder with a prevalence estimated at 2.29% in China. The gene responsible for this disorder has not been elucidated. To find the disease gene, we ascertained two Chinese IV families. Linkage analysis identified an IV locus on chromosome 1q22 with a maximum two-point Lod score of 2.47 at D1S1653 (theta=0.00). Haplotype analysis placed the critical region in a 7-cM interval defined by D1S1653 and D1S2675. These results provide the basis for further identifying the gene responsible for IV disorder.

  7. Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis

    OpenAIRE

    Klein, Alison P.; Kovac, Ilija; Sorant, Alexa JM; Baffoe-Bonnie, Agnes; Doan, Betty Q; Ibay, Grace; Lockwood, Erica; Mandal, Diptasri; Santhosh, Lekshmi; Weissbecker, Karen; Woo, Jessica; Zambelli-Weiner, April; Zhang, Jie; Naiman, Daniel Q.; Malley, James

    2003-01-01

    Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each...

  8. Linkage analysis and the study of Mendelian disease in the era of whole exome and genome sequencing.

    Science.gov (United States)

    Teare, M Dawn; Santibañez Koref, Mauro F

    2014-09-01

    Whole exome and whole genome sequencing are now routinely used in the study of inherited disease, and some of their major successes have been the identification of genes involved in disease predisposition in pedigrees where disease seems to follow Mendelian inheritance patterns. These successes include scenarios where only a single individual was sequenced and raise the question whether linkage analysis has become superfluous. Linkage analysis requires genome-wide genotyping on family-based data, and traditionally the linkage analysis was performed before the targeting sequencing stage. However, methods are emerging that seek to exploit the capability of linkage analysis to integrate data both across individuals and across pedigrees. This ability has been exploited to select samples used for sequencing studies and to identify among the variants uncovered by sequencing those mapping to regions likely to contain the gene of interest and, more generally, to improve variant detection. So, although the formal isolated linkage analysis stage is less commonly seen, when uncovering the genetic basis of Mendelian disease, methods relying heavily on genetic linkage analysis principles are being integrated directly into the whole mapping process ranging from sample selection to variant calling and filtering. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. How Are Teachers Teaching? A Nonparametric Approach

    Science.gov (United States)

    De Witte, Kristof; Van Klaveren, Chris

    2014-01-01

    This paper examines which configuration of teaching activities maximizes student performance. For this purpose a nonparametric efficiency model is formulated that accounts for (1) self-selection of students and teachers in better schools and (2) complementary teaching activities. The analysis distinguishes both individual teaching (i.e., a…

  10. Decompounding random sums: A nonparametric approach

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted; Pitts, Susan M.

    review a number of applications and consider the nonlinear inverse problem of inferring the cumulative distribution function of the components in the random sum. We review the existing literature on non-parametric approaches to the problem. The models amenable to the analysis are generalized considerably...

  11. How Are Teachers Teaching? A Nonparametric Approach

    Science.gov (United States)

    De Witte, Kristof; Van Klaveren, Chris

    2014-01-01

    This paper examines which configuration of teaching activities maximizes student performance. For this purpose a nonparametric efficiency model is formulated that accounts for (1) self-selection of students and teachers in better schools and (2) complementary teaching activities. The analysis distinguishes both individual teaching (i.e., a…

  12. Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data.

    Science.gov (United States)

    Coussens, Nathan P; Schuck, Peter; Zhao, Huaying

    2012-09-01

    Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally, a comparison of data from different experimental strategies illustrates the benefit of conducting experiments at a range of temperatures.

  13. The 12-item World Health Organization Disability Assessment Schedule II (WHO-DAS II: a nonparametric item response analysis

    Directory of Open Access Journals (Sweden)

    Fernandez Ana

    2010-05-01

    Full Text Available Abstract Background Previous studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF in men and women. Methods The participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves and their options (option characteristic curves in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item. Results Item response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items. Conclusions All WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.

  14. A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen Family study

    Directory of Open Access Journals (Sweden)

    Claudia Tamar Silva

    2016-11-01

    Full Text Available Electrocardiogram (ECG measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies (GWAS of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF. Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05, one for QRS interval (1p35, LOD = 2.52 and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29. Fine-mapping using exome sequence data identified a C > G missense variant (c.713C>G, p.Ser238Cys in the FCRL2 gene associated with QT (rs74608430; P = 2.8 ×10-4, minor allele frequency = 0.019. Heritability analysis demonstrated that the SNP explained 2.42% of the trait’s genetic variability in ERF (P = 0.02. Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3 and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 ×10-3. Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval.

  15. 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...

  16. Nonparametric tests for censored data

    CERN Document Server

    Bagdonavicus, Vilijandas; Nikulin, Mikhail

    2013-01-01

    This book concerns testing hypotheses in non-parametric models. Generalizations of many non-parametric tests to the case of censored and truncated data are considered. Most of the test results are proved and real applications are illustrated using examples. Theories and exercises are provided. The incorrect use of many tests applying most statistical software is highlighted and discussed.

  17. The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

    Science.gov (United States)

    Christensen, G B; Knight, S; Camp, N J

    2009-11-01

    We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

  18. Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis.

    Science.gov (United States)

    Borgulová, Irena; Putzová, Martina; Soldatova, Inna; Stejskal, David

    2017-08-07

    To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Neurofibromatosis type I (NFI) in Israeli families: Linkage analysis as a diagnostic tool

    Energy Technology Data Exchange (ETDEWEB)

    Elyakim, S.; Lerer, I.; Zlotogora, J.; Sagi, M.; Merin, S.; Abeliovich, D. [Hadassah Univ. Hospital, Jerusalem (Israel); Gelman-Kohan, Z. [Hebrew Univ. Hadassah Medical School, Rehovot (Israel)

    1994-12-01

    Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI-bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI-bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome. 49 refs., 4 figs., 3 tabs.

  20. Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

    Science.gov (United States)

    Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

    2008-02-01

    The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

  1. An approach to incorporate linkage disequilibrium structure into genomic association analysis

    Institute of Scientific and Technical Information of China (English)

    Fengyu Zhang; Diane Wagener

    2008-01-01

    In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-basod correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.

  2. Asymptotic theory of nonparametric regression estimates with censored data

    Institute of Scientific and Technical Information of China (English)

    施沛德; 王海燕; 张利华

    2000-01-01

    For regression analysis, some useful Information may have been lost when the responses are right censored. To estimate nonparametric functions, several estimates based on censored data have been proposed and their consistency and convergence rates have been studied in literat黵e, but the optimal rates of global convergence have not been obtained yet. Because of the possible Information loss, one may think that it is impossible for an estimate based on censored data to achieve the optimal rates of global convergence for nonparametric regression, which were established by Stone based on complete data. This paper constructs a regression spline estimate of a general nonparametric regression f unction based on right-censored response data, and proves, under some regularity condi-tions, that this estimate achieves the optimal rates of global convergence for nonparametric regression. Since the parameters for the nonparametric regression estimate have to be chosen based on a data driven criterion, we also obtai

  3. 2nd Conference of the International Society for Nonparametric Statistics

    CERN Document Server

    Manteiga, Wenceslao; Romo, Juan

    2016-01-01

    This volume collects selected, peer-reviewed contributions from the 2nd Conference of the International Society for Nonparametric Statistics (ISNPS), held in Cádiz (Spain) between June 11–16 2014, and sponsored by the American Statistical Association, the Institute of Mathematical Statistics, the Bernoulli Society for Mathematical Statistics and Probability, the Journal of Nonparametric Statistics and Universidad Carlos III de Madrid. The 15 articles are a representative sample of the 336 contributed papers presented at the conference. They cover topics such as high-dimensional data modelling, inference for stochastic processes and for dependent data, nonparametric and goodness-of-fit testing, nonparametric curve estimation, object-oriented data analysis, and semiparametric inference. The aim of the ISNPS 2014 conference was to bring together recent advances and trends in several areas of nonparametric statistics in order to facilitate the exchange of research ideas, promote collaboration among researchers...

  4. Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

    Science.gov (United States)

    Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

    2017-01-01

    It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

  5. Linkage Map Construction and Quantitative Trait Locus Analysis of Agronomic and Fiber Quality Traits in Cotton

    Directory of Open Access Journals (Sweden)

    Michael A. Gore

    2014-03-01

    Full Text Available The superior fiber properties of L. serve as a source of novel variation for improving fiber quality in Upland cotton ( L., but introgression from has been largely unsuccessful due to hybrid breakdown and a lack of genetic and genomic resources. In an effort to overcome these limitations, we constructed a linkage map and conducted a quantitative trait locus (QTL analysis of 10 agronomic and fiber quality traits in a recombinant inbred mapping population derived from a cross between TM-1, an Upland cotton line, and NM24016, an elite line with stabilized introgression from . The linkage map consisted of 429 simple-sequence repeat (SSR and 412 genotyping-by-sequencing (GBS-based single-nucleotide polymorphism (SNP marker loci that covered half of the tetraploid cotton genome. Notably, the 841 marker loci were unevenly distributed among the 26 chromosomes of tetraploid cotton. The 10 traits evaluated on the TM-1 × NM24016 population in a multienvironment trial were highly heritable, and most of the fiber traits showed considerable transgressive variation. Through the QTL analysis, we identified a total of 28 QTLs associated with the 10 traits. Our study provides a novel resource that can be used by breeders and geneticists for the genetic improvement of agronomic and fiber quality traits in Upland cotton.

  6. Creative Activities in Music – A Genome-Wide Linkage Analysis

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  7. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Directory of Open Access Journals (Sweden)

    Jaana Oikkonen

    Full Text Available Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases, 4q22.1 for composing (LOD 2.15, 103 cases and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases. Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA at 18q21 (LOD 3.09, 149 cases, which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD, which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We

  8. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  9. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  10. Nonparametric statistical methods using R

    CERN Document Server

    Kloke, John

    2014-01-01

    A Practical Guide to Implementing Nonparametric and Rank-Based ProceduresNonparametric Statistical Methods Using R covers traditional nonparametric methods and rank-based analyses, including estimation and inference for models ranging from simple location models to general linear and nonlinear models for uncorrelated and correlated responses. The authors emphasize applications and statistical computation. They illustrate the methods with many real and simulated data examples using R, including the packages Rfit and npsm.The book first gives an overview of the R language and basic statistical c

  11. Setting up Multiplex Panels for Genetic Testing of Familial Hy¬pertrophic Cardiomyopathy Based on Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Hoorieh SAGHAFI

    2016-03-01

    Full Text Available Background: Familial hypertrophic cardiomyopathy (HCM is caused by mutations in genes encoding cardiac sarcomere proteins. Nowadays genetic testing of HCM plays an important role in clinical practice by contributing to the diagnosis, prognosis, and screening of high-risk individuals. The aim of this study was developing a reliable testing strategy for HCM based on linkage analysis and appropriate for Iranian population.Methods: Six panels of four microsatellite markers surrounding MYH7, MYBPC3, TNNT2, TNNI3, TPM1, and MYL2 genes (24 markers in total were selected for multiplex PCR and fragment length analysis. Characteristics of markers and informativeness of the panels were evaluated in 50 unrelated Iranians. The efficacy of the strategy was verified in a family with HCM.Results: All markers were highly polymorphic. The panels were informative in 96-100% of samples. Multipoint linkage analysis excluded the linkage between the disease and all six genes by obtaining maximum LOD score ≤-2.Conclusion: This study suggests a reliable genetic testing method based on linkage analysis between 6 sarcomere genes and familial HCM. It could be applied for diagnostic, predictive, or screening testing in clinical setting. Keywords: Cardiomyopathy, Hypertrophic, Genetic linkage, Diagnosis 

  12. Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, L.S.; Hoffman, E.P. (Univ. of Pittsburgh Schoool of Medicine, Pittsburgh, PA (United States)); Tarleton, J. (Self Memorial Hospital, Greenwood, SC (United States)); Popovich, B. (Children' s Hosptial and Health Center, San Diego, CA (United States)); Seltzer, W.K. (Univ. of Colorado Health Sciences Center, Denver, CO (United States))

    1992-10-01

    The authors have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)[sub n] repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. The authors present the successful application of this protocol in families who proved refractory to more traditional analyses. 22 refs., 3 figs.

  13. International comparisons of the technical efficiency of the hospital sector: panel data analysis of OECD countries using parametric and non-parametric approaches.

    Science.gov (United States)

    Varabyova, Yauheniya; Schreyögg, Jonas

    2013-09-01

    There is a growing interest in the cross-country comparisons of the performance of national health care systems. The present work provides a comparison of the technical efficiency of the hospital sector using unbalanced panel data from OECD countries over the period 2000-2009. The estimation of the technical efficiency of the hospital sector is performed using nonparametric data envelopment analysis (DEA) and parametric stochastic frontier analysis (SFA). Internal and external validity of findings is assessed by estimating the Spearman rank correlations between the results obtained in different model specifications. The panel-data analyses using two-step DEA and one-stage SFA show that countries, which have higher health care expenditure per capita, tend to have a more technically efficient hospital sector. Whether the expenditure is financed through private or public sources is not related to the technical efficiency of the hospital sector. On the other hand, the hospital sector in countries with higher income inequality and longer average hospital length of stay is less technically efficient. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. A Critical Look at the Mass-Metallicity-SFR Relation in the Local Universe: Non-parametric Analysis Framework and Confounding Systematics

    CERN Document Server

    Salim, Samir; Ly, Chun; Brinchmann, Jarle; Davé, Romeel; Dickinson, Mark; Salzer, John J; Charlot, Stéphane

    2014-01-01

    It has been proposed that the mass-metallicity relation of galaxies exhibits a secondary dependence on star formation rate (SFR), and that the resulting M-Z-SFR relation may be redshift-invariant, i.e., "fundamental." However, conflicting results on the character of the SFR dependence, and whether it exists, have been reported. To gain insight into the origins of the conflicting results, we (a) devise a non-parametric, astrophysically-motivated analysis framework based on the offset from the star-forming ("main") sequence at a given stellar mass (relative specific SFR), (b) apply this methodology and perform a comprehensive re-analysis of the local M-Z-SFR relation, based on SDSS, GALEX, and WISE data, and (c) study the impact of sample selection, and of using different metallicity and SFR indicators. We show that metallicity is anti-correlated with specific SFR regardless of the indicators used. We do not find that the relation is spurious due to correlations arising from biased metallicity measurements, or ...

  15. Homothetic Efficiency and Test Power: A Non-Parametric Approach

    NARCIS (Netherlands)

    J. Heufer (Jan); P. Hjertstrand (Per)

    2015-01-01

    markdownabstract__Abstract__ We provide a nonparametric revealed preference approach to demand analysis based on homothetic efficiency. Homotheticity is a useful restriction but data rarely satisfies testable conditions. To overcome this we provide a way to estimate homothetic efficiency of

  16. A genome-wide linkage study of bipolar disorder and co-morbid migraine

    DEFF Research Database (Denmark)

    Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger

    2010-01-01

    on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In additionwe identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes...... Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....

  17. Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.

    OpenAIRE

    Mazoyer, S; Lalle, P.; Narod, S. A.; Bignon, Y J; Courjal, F; Jamot, B.; Dutrillaux, B.; Stoppa-Lyonnett, D; Sobol, H

    1993-01-01

    Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.

  18. Genome-Wide Linkage Analysis Identifies Loci for Physical Appearance Traits in Chickens.

    Science.gov (United States)

    Sun, Yanfa; Liu, Ranran; Zhao, Guiping; Zheng, Maiqing; Sun, Yan; Yu, Xiaoqiong; Li, Peng; Wen, Jie

    2015-08-06

    Physical appearance traits, such as feather-crested head, comb size and type, beard, wattles size, and feathered feet, are used to distinguish between breeds of chicken and also may be associated with economic traits. In this study, a genome-wide linkage analysis was used to identify candidate regions and genes for physical appearance traits and to potentially provide further knowledge of the molecular mechanisms that underlie these traits. The linkage analysis was conducted with an F2 population derived from Beijing-You chickens and a commercial broiler line. Single-nucleotide polymorphisms were analyzed using the Illumina 60K Chicken SNP Beadchip. The data were used to map quantitative trait loci and genes for six physical appearance traits. A 10-cM/0.51-Mb region (0.0-10.0 cM/0.00-0.51 Mb) with 1% genome-wide significant level on LGE22C19W28_E50C23 linkage group (LGE22) for crest trait was identified, which is likely very closely linked to the HOXC8. A QTL with 5% chromosome-wide significant level for comb weight, which partly overlaps with a region identified in a previous study, was identified at 74 cM/25.55 Mb on chicken (Gallus gallus; GG) chromosome 3 (i.e., GGA3). For beard and wattles traits, an identical region 11 cM/2.23 Mb (0.0-11.0 cM/0.00-2.23 Mb) including WNT3 and GH genes on GGA27 was identified. Two QTL with 1% genome-wide significant level for feathered feet trait, one 9-cM/2.80-Mb (48.0-57.0/13.40-16.20 Mb) region on GGA13, and another 12-cM/1.45-Mb (41.0-53.0 cM/11.37-12.82 Mb) region on GGA15 were identified. These candidate regions and genes provide important genetic information for the physical appearance traits in chicken. Copyright © 2015 Sun et al.

  19. A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.

    Science.gov (United States)

    Hu, Hao; Roach, Jared C; Coon, Hilary; Guthery, Stephen L; Voelkerding, Karl V; Margraf, Rebecca L; Durtschi, Jacob D; Tavtigian, Sean V; Shankaracharya; Wu, Wilfred; Scheet, Paul; Wang, Shuoguo; Xing, Jinchuan; Glusman, Gustavo; Hubley, Robert; Li, Hong; Garg, Vidu; Moore, Barry; Hood, Leroy; Galas, David J; Srivastava, Deepak; Reese, Martin G; Jorde, Lynn B; Yandell, Mark; Huff, Chad D

    2014-07-01

    High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.

  20. Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus...

  1. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  2. Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA

    Directory of Open Access Journals (Sweden)

    Ettie M. Lipner

    2015-01-01

    Full Text Available We conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D. We analyzed 415 families (2,008 individuals previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For retinopathy, two linkage peaks were mapped: one located at the HLA region and another novel locus telomeric to HLA. For nephropathy, a linkage peak centromeric to HLA was mapped, but the linkage peak telomeric to HLA seen in retinopathy was absent. Because of the strong association of T1D with DRB1*03:01 and DRB1*04:01, we stratified our analyses based on families whose probands were positive for DRB1*03:01 or DRB1*04:01. When analyzing the DRB1*03:01-positive retinopathy families, in addition to the novel telomeric locus, one centromeric to HLA was identified at the same location as the nephropathy peak. When we stratified on DRB1*04:01-positive families, the HLA telomeric peak strengthened but the centromeric peak disappeared. Our findings showed that HLA and non-HLA loci on chromosome 6 are involved in T1D complications’ expression. While the HLA region is a major contributor to the expression of T1D, our results suggest an interaction between specific HLA alleles and other loci that influence complications’ expression.

  3. Polymorphism analysis of microsatellites and construction of linkage map in part regions of four chromosomes in chicken

    Institute of Scientific and Technical Information of China (English)

    WANG Shouzhi; LI Hui; LI Ning; GAO Yu; DU Zhiqiang; GU Zhiliang; WANG Qigui; LI Zhihui; WANG Ying

    2007-01-01

    Based on chicken' consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDFS and APOA1 in 4 chromosomes (chromosome 5, 7, 8 and 24) were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity (H) of markers was between 0.3116 and 0.9148. Polymorphic information content (PIC) varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci (QTL) responsible for economically important traits in chicken.

  4. 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

  5. A note on the use of the non-parametric Wilcoxon-Mann-Whitney test in the analysis of medical studies

    Directory of Open Access Journals (Sweden)

    Kühnast, Corinna

    2008-04-01

    Full Text Available Background: Although non-normal data are widespread in biomedical research, parametric tests unnecessarily predominate in statistical analyses. Methods: We surveyed five biomedical journals and – for all studies which contain at least the unpaired t-test or the non-parametric Wilcoxon-Mann-Whitney test – investigated the relationship between the choice of a statistical test and other variables such as type of journal, sample size, randomization, sponsoring etc. Results: The non-parametric Wilcoxon-Mann-Whitney was used in 30% of the studies. In a multivariable logistic regression the type of journal, the test object, the scale of measurement and the statistical software were significant. The non-parametric test was more common in case of non-continuous data, in high-impact journals, in studies in humans, and when the statistical software is specified, in particular when SPSS was used.

  6. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-01

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

  7. The Use of Information Transmission as Nonparametric Correlation in the Analysis of Complex Behavior: A Preliminary Report.

    Science.gov (United States)

    1980-05-01

    kEgeering Psychology Programs a dOffice of Naval Research (Code. 455) Arlington, VA 22217 1 14 MONITORING AGENCY NAME A ADORESS(hI diferent 0000...STATEMENT (of the Abe~ag @amed tol 8110" 2. it Aliment *001 Repel) Approved for public release; distribution unlimited. If. SUPPLEMENTARY NOTES I...Structure ........ I i Introduction J Experimental psychology has developed a sophisticated set of experimental designs for the analysis of behaviour when

  8. NONPARAMETRIC ESTIMATION OF CHARACTERISTICS OF PROBABILITY DISTRIBUTIONS

    Directory of Open Access Journals (Sweden)

    Orlov A. I.

    2015-10-01

    Full Text Available The article is devoted to the nonparametric point and interval estimation of the characteristics of the probabilistic distribution (the expectation, median, variance, standard deviation, variation coefficient of the sample results. Sample values are regarded as the implementation of independent and identically distributed random variables with an arbitrary distribution function having the desired number of moments. Nonparametric analysis procedures are compared with the parametric procedures, based on the assumption that the sample values have a normal distribution. Point estimators are constructed in the obvious way - using sample analogs of the theoretical characteristics. Interval estimators are based on asymptotic normality of sample moments and functions from them. Nonparametric asymptotic confidence intervals are obtained through the use of special output technology of the asymptotic relations of Applied Statistics. In the first step this technology uses the multidimensional central limit theorem, applied to the sums of vectors whose coordinates are the degrees of initial random variables. The second step is the conversion limit multivariate normal vector to obtain the interest of researcher vector. At the same considerations we have used linearization and discarded infinitesimal quantities. The third step - a rigorous justification of the results on the asymptotic standard for mathematical and statistical reasoning level. It is usually necessary to use the necessary and sufficient conditions for the inheritance of convergence. This article contains 10 numerical examples. Initial data - information about an operating time of 50 cutting tools to the limit state. Using the methods developed on the assumption of normal distribution, it can lead to noticeably distorted conclusions in a situation where the normality hypothesis failed. Practical recommendations are: for the analysis of real data we should use nonparametric confidence limits

  9. Detection of Duchenne/Becker Muscular Dystrophy Carriers in a Group of Iranian Families by Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Fardeen Ali Malayeri

    2011-03-01

    Full Text Available This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.

  10. Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

    Science.gov (United States)

    A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

  11. UN ANÁLISIS NO PARAMÉTRICO DE ÍTEMS DE LA PRUEBA DEL BENDER/A NONPARAMETRIC ITEM ANALYSIS OF THE BENDER GESTALT TEST MODIFIED

    Directory of Open Access Journals (Sweden)

    César Merino Soto

    2009-05-01

    Full Text Available Resumen:La presente investigación hace un estudio psicométrico de un nuevo sistema de calificación de la Prueba Gestáltica del Bendermodificada para niños, que es el Sistema de Calificación Cualitativa (Brannigan y Brunner, 2002, en un muestra de 244 niñosingresantes a primer grado de primaria en cuatro colegios públicos, ubicados en Lima. El enfoque usado es un análisis noparamétrico de ítems mediante el programa Testgraf (Ramsay, 1991. Los resultados indican niveles apropiados deconsistencia interna, identificándose la unidimensionalidad, y el buen nivel discriminativo de las categorías de calificación deeste Sistema Cualitativo. No se hallaron diferencias demográficas respecto al género ni la edad. Se discuten los presenteshallazgos en el contexto del potencial uso del Sistema de Calificación Cualitativa y del análisis no paramétrico de ítems en lainvestigación psicométrica.AbstracThis research designs a psychometric study of a new scoring system of the Bender Gestalt test modified to children: it is theQualitative Scoring System (Brannigan & Brunner, 2002, in a sample of 244 first grade children of primary level, in four public school of Lima. The approach aplied is the nonparametric item analysis using The test graft computer program (Ramsay, 1991. Our findings point to good levels of internal consistency, unidimensionality and good discriminative level ofthe categories of scoring from the Qualitative Scoring System. There are not demographic differences between gender or age.We discuss our findings within the context of the potential use of the Qualitative Scoring System and of the nonparametricitem analysis approach in the psychometric research.

  12. A nonparametric method for detecting fixations and saccades using cluster analysis: removing the need for arbitrary thresholds.

    Science.gov (United States)

    König, Seth D; Buffalo, Elizabeth A

    2014-04-30

    Eye tracking is an important component of many human and non-human primate behavioral experiments. As behavioral paradigms have become more complex, including unconstrained viewing of natural images, eye movements measured in these paradigms have become more variable and complex as well. Accordingly, the common practice of using acceleration, dispersion, or velocity thresholds to segment viewing behavior into periods of fixations and saccades may be insufficient. Here we propose a novel algorithm, called Cluster Fix, which uses k-means cluster analysis to take advantage of the qualitative differences between fixations and saccades. The algorithm finds natural divisions in 4 state space parameters-distance, velocity, acceleration, and angular velocity-to separate scan paths into periods of fixations and saccades. The number and size of clusters adjusts to the variability of individual scan paths. Cluster Fix can detect small saccades that were often indistinguishable from noisy fixations. Local analysis of fixations helped determine the transition times between fixations and saccades. Because Cluster Fix detects natural divisions in the data, predefined thresholds are not needed. A major advantage of Cluster Fix is the ability to precisely identify the beginning and end of saccades, which is essential for studying neural activity that is modulated by or time-locked to saccades. Our data suggest that Cluster Fix is more sensitive than threshold-based algorithms but comes at the cost of an increase in computational time. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  14. Semi- and Nonparametric ARCH Processes

    Directory of Open Access Journals (Sweden)

    Oliver B. Linton

    2011-01-01

    Full Text Available ARCH/GARCH modelling has been successfully applied in empirical finance for many years. This paper surveys the semiparametric and nonparametric methods in univariate and multivariate ARCH/GARCH models. First, we introduce some specific semiparametric models and investigate the semiparametric and nonparametrics estimation techniques applied to: the error density, the functional form of the volatility function, the relationship between mean and variance, long memory processes, locally stationary processes, continuous time processes and multivariate models. The second part of the paper is about the general properties of such processes, including stationary conditions, ergodic conditions and mixing conditions. The last part is on the estimation methods in ARCH/GARCH processes.

  15. Analysis of stock market linkages: evidence from the selected CEE markets

    Directory of Open Access Journals (Sweden)

    Michaela Chocholatá

    2013-04-01

    Full Text Available This paper analyses the stock market linkages of the selected Central and Eastern European (CEE markets (Czech Republic – PX, Hungary – BUX and Poland – WIG20 with the Western European stock market represented by the German DAX and studies also the co-movement between the individual CEE countries’ stock markets. The dynamic conditional correlation (DCC models were used to model the co-movements and thereafter in some cases the smooth transition analysis was carried out in order to capture how these correla-tions evolve over time. The analysis was based on weekly data over the sample period Jan-uary 3rd, 1997 – November 29th, 2013 (883 observations. In the first step the asymmetric univariate autoregressive conditional heteroscedasticity model of Glosten, Jagannathan and Runkle (GJR was estimated for individual stock return series. The results of the DCC-GJR models estimated in the next step show almost in all analysed cases the increasing lev-el of conditional correlations. In four cases (BUX_DAX, WIG20_DAX, BUX_PX and PX_WIG20 the DCC series were identified to be nonstationary – I(1 and nonlinear lo-gistic smooth transition regression (LSTR model was used to capture the gradual transi-tion towards greater co-movements and to find out if the increasing level of DCC could be attributed to the accession of these countries into the European Union (EU in May 2004.

  16. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Perri, Alessandra; Andersson, Ulf; Nell, Phillip C.;

    This paper investigates local vertical linkages of foreign subsidiaries and the dual role of such linkages as conduits for learning as well as potential channels for spillovers to competitors. On the basis of data from 97 subsidiaries, we analyze the quality of such linkages under varying levels...... of competition and subsidiary capabilities. Our theoretical development and the results from the analysis document a far more complex and dynamic relationship between levels of competition and MNCs’ local participation in knowledge intensive activities, i.e. learning and spillovers, than previous studies do. We...

  17. Within-family outliers: segregating alleles or environmental effects? A linkage analysis of height from 5815 sibling pairs.

    Science.gov (United States)

    Benyamin, Beben; Perola, Markus; Cornes, Belinda K; Madden, Pamela Af; Palotie, Aarno; Nyholt, Dale R; Montgomery, Grant W; Peltonen, Leena; Martin, Nicholas G; Visscher, Peter M

    2008-04-01

    Most information in linkage analysis for quantitative traits comes from pairs of relatives that are phenotypically most discordant or concordant. Confounding this, within-family outliers from non-genetic causes may create false positives and negatives. We investigated the influence of within-family outliers empirically, using one of the largest genome-wide linkage scans for height. The subjects were drawn from Australian twin cohorts consisting of 8447 individuals in 2861 families, providing a total of 5815 possible pairs of siblings in sibships. A variance component linkage analysis was performed, either including or excluding the within-family outliers. Using the entire dataset, the largest LOD scores were on chromosome 15q (LOD 2.3) and 11q (1.5). Excluding within-family outliers increased the LOD score for most regions, but the LOD score on chromosome 15 decreased from 2.3 to 1.2, suggesting that the outliers may create false negatives and false positives, although rare alleles of large effect may also be an explanation. Several regions suggestive of linkage to height were found after removing the outliers, including 1q23.1 (2.0), 3q22.1 (1.9) and 5q32 (2.3). We conclude that the investigation of the effect of within-family outliers, which is usually neglected, should be a standard quality control measure in linkage analysis for complex traits and may reduce the noise for the search of common variants of modest effect size as well as help identify rare variants of large effect and clinical significance. We suggest that the effect of within-family outliers deserves further investigation via theoretical and simulation studies.

  18. Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Parolini, O.; Lassiter, G.L.; Henry, M.J.; Conley, M.E. (Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Hejtmancik, J.F. (National Inst. of Health, Bethesda, MD (United States)); Allen, R.C.; Belmont, J.W. (Baylor College of Medicine, Houston, TX (United States)); Barker, D.F. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

  19. Nonparametric estimation of ultrasound pulses

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Leeman, Sidney

    1994-01-01

    An algorithm for nonparametric estimation of 1D ultrasound pulses in echo sequences from human tissues is derived. The technique is a variation of the homomorphic filtering technique using the real cepstrum, and the underlying basis of the method is explained. The algorithm exploits a priori...

  20. Testing discontinuities in nonparametric regression

    KAUST Repository

    Dai, Wenlin

    2017-01-19

    In nonparametric regression, it is often needed to detect whether there are jump discontinuities in the mean function. In this paper, we revisit the difference-based method in [13 H.-G. Müller and U. Stadtmüller, Discontinuous versus smooth regression, Ann. Stat. 27 (1999), pp. 299–337. doi: 10.1214/aos/1018031100

  1. Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis

    Directory of Open Access Journals (Sweden)

    Zafar Ali

    2011-01-01

    Full Text Available The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1. The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024 in vicinity of mental retardation (MR locus (MRT1/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE. The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.

  2. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.

    Science.gov (United States)

    Sivakumaran, Theru A; Lesperance, Marci M

    2004-11-01

    In this report, we present the haplotype and linkage disequilibrium (LD) pattern in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld syndrome (EVC) gene region. We genotyped eight different single nucleotide polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most having a frequency >25%. A total of 37 haplotypes were derived from these eight polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD analysis showed a weak but significant LD between markers located about 243 kb apart in this region. The LD was significant between markers spaced about 208 kb apart in EVC, whereas no LD was found between a pair of markers located about 5 kb apart in CRMP1. However, in general, LD correlated with the distance between loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

  3. Cross border hospital use: analysis using data linkage across four Australian states.

    Science.gov (United States)

    Spilsbury, Katrina; Rosman, Diana; Alan, Janine; Boyd, James H; Ferrante, Anna M; Semmens, James B

    2015-06-15

    To determine the quality and effectiveness of national data linkage capacity by performing a proof-of-concept project investigating cross-border hospital use and hospital-related deaths. Analysis of person-level linked hospital separation and death registration data of all public and private hospital patients in New South Wales, Queensland and Western Australia and of public hospital patients in South Australia, totalling 7.7 million hospital patients from 1 July 2004 to 30 June 2009. Counts and proportions of hospital stays and patient movement patterns. 223 262 patients (3.0%) travelled across a state border to attend hospitals, in particular, far northern and western NSW patients travelling to Queensland and SA hospitals, respectively. A further 48 575 patients (0.6%) moved their place of residence interstate between hospital visits, particularly to and from areas associated with major mining and tourism industries. Over 11 000 cross-border hospital transfers were also identified. Of patients who travelled across a state border to hospital, 2800 (1.3%) died in that hospital. An additional 496 deaths recorded in one jurisdiction occurred within 30 days of hospital separation from another jurisdiction. Access to person-level data linked across jurisdictions identified geographical hot spots of cross-border hospital use and hospital-related deaths in Australia. This has implications for planning of health service delivery and for longitudinal follow-up studies, particularly those involving mobile populations.

  4. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    Energy Technology Data Exchange (ETDEWEB)

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

  5. Mokken scale analysis of mental health and well-being questionnaire item responses: a non-parametric IRT method in empirical research for applied health researchers

    Directory of Open Access Journals (Sweden)

    Stochl Jan

    2012-06-01

    Full Text Available Abstract Background Mokken scaling techniques are a useful tool for researchers who wish to construct unidimensional tests or use questionnaires that comprise multiple binary or polytomous items. The stochastic cumulative scaling model offered by this approach is ideally suited when the intention is to score an underlying latent trait by simple addition of the item response values. In our experience, the Mokken model appears to be less well-known than for example the (related Rasch model, but is seeing increasing use in contemporary clinical research and public health. Mokken's method is a generalisation of Guttman scaling that can assist in the determination of the dimensionality of tests or scales, and enables consideration of reliability, without reliance on Cronbach's alpha. This paper provides a practical guide to the application and interpretation of this non-parametric item response theory method in empirical research with health and well-being questionnaires. Methods Scalability of data from 1 a cross-sectional health survey (the Scottish Health Education Population Survey and 2 a general population birth cohort study (the National Child Development Study illustrate the method and modeling steps for dichotomous and polytomous items respectively. The questionnaire data analyzed comprise responses to the 12 item General Health Questionnaire, under the binary recoding recommended for screening applications, and the ordinal/polytomous responses to the Warwick-Edinburgh Mental Well-being Scale. Results and conclusions After an initial analysis example in which we select items by phrasing (six positive versus six negatively worded items we show that all items from the 12-item General Health Questionnaire (GHQ-12 – when binary scored – were scalable according to the double monotonicity model, in two short scales comprising six items each (Bech’s “well-being” and “distress” clinical scales. An illustration of ordinal item analysis

  6. Mokken scale analysis of mental health and well-being questionnaire item responses: a non-parametric IRT method in empirical research for applied health researchers.

    Science.gov (United States)

    Stochl, Jan; Jones, Peter B; Croudace, Tim J

    2012-06-11

    Mokken scaling techniques are a useful tool for researchers who wish to construct unidimensional tests or use questionnaires that comprise multiple binary or polytomous items. The stochastic cumulative scaling model offered by this approach is ideally suited when the intention is to score an underlying latent trait by simple addition of the item response values. In our experience, the Mokken model appears to be less well-known than for example the (related) Rasch model, but is seeing increasing use in contemporary clinical research and public health. Mokken's method is a generalisation of Guttman scaling that can assist in the determination of the dimensionality of tests or scales, and enables consideration of reliability, without reliance on Cronbach's alpha. This paper provides a practical guide to the application and interpretation of this non-parametric item response theory method in empirical research with health and well-being questionnaires. Scalability of data from 1) a cross-sectional health survey (the Scottish Health Education Population Survey) and 2) a general population birth cohort study (the National Child Development Study) illustrate the method and modeling steps for dichotomous and polytomous items respectively. The questionnaire data analyzed comprise responses to the 12 item General Health Questionnaire, under the binary recoding recommended for screening applications, and the ordinal/polytomous responses to the Warwick-Edinburgh Mental Well-being Scale. After an initial analysis example in which we select items by phrasing (six positive versus six negatively worded items) we show that all items from the 12-item General Health Questionnaire (GHQ-12)--when binary scored--were scalable according to the double monotonicity model, in two short scales comprising six items each (Bech's "well-being" and "distress" clinical scales). An illustration of ordinal item analysis confirmed that all 14 positively worded items of the Warwick-Edinburgh Mental

  7. Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, D.B.; Ossowski, V.; Janssen, R.C.; Knowler, W.C.; Bogardus, C. [National Inst. of Health, Phoenix, AZ (United States)

    1995-12-04

    Sib-pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20. Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3. cM region that includes D20S98 and D20S66. Using all possible sib-pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height. Single-strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height. Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single-strand conformational polymorphism (SSCP) analysis. This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample. No significant differences in height were noted in persons carrying either allele. This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. 33 refs., 2 figs., 2 tabs.

  8. Non-Parametric Inference in Astrophysics

    CERN Document Server

    Wasserman, L H; Nichol, R C; Genovese, C; Jang, W; Connolly, A J; Moore, A W; Schneider, J; Wasserman, Larry; Miller, Christopher J.; Nichol, Robert C.; Genovese, Chris; Jang, Woncheol; Connolly, Andrew J.; Moore, Andrew W.; Schneider, Jeff; group, the PICA

    2001-01-01

    We discuss non-parametric density estimation and regression for astrophysics problems. In particular, we show how to compute non-parametric confidence intervals for the location and size of peaks of a function. We illustrate these ideas with recent data on the Cosmic Microwave Background. We also briefly discuss non-parametric Bayesian inference.

  9. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico

    2012-01-01

    Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1...... ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared...... Findings: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all...

  10. Comparing parametric and nonparametric regression methods for panel data

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    We investigate and compare the suitability of parametric and non-parametric stochastic regression methods for analysing production technologies and the optimal firm size. Our theoretical analysis shows that the most commonly used functional forms in empirical production analysis, Cobb-Douglas and......We investigate and compare the suitability of parametric and non-parametric stochastic regression methods for analysing production technologies and the optimal firm size. Our theoretical analysis shows that the most commonly used functional forms in empirical production analysis, Cobb......-Douglas and Translog, are unsuitable for analysing the optimal firm size. We show that the Translog functional form implies an implausible linear relationship between the (logarithmic) firm size and the elasticity of scale, where the slope is artificially related to the substitutability between the inputs...... rejects both the Cobb-Douglas and the Translog functional form, while a recently developed nonparametric kernel regression method with a fully nonparametric panel data specification delivers plausible results. On average, the nonparametric regression results are similar to results that are obtained from...

  11. Nonparametric Maize TFP Measurement Analysis and Countermeasures%玉米全要素生产率非参数测算分析及对策

    Institute of Scientific and Technical Information of China (English)

    曲会朋; 李宁; 田玉英

    2014-01-01

    玉米生产受到诸多投入要素的限制与影响,如种子、秧苗、劳动力、土地、农药、化肥、农膜、机械设备、畜力和其他物质投入等,提高这些因素的投入-产出效率水平对于促进玉米高效持续增产至关重要。为此,在对中美两国玉米生产成本与单产时序比较的基础上,利用基于DEA 的非参数前沿面效率分解方法对全国主要地区的玉米全要素生产效率问题进行了实证分析,从纵向时间序列和横向不同区域两个视角研究了我国玉米生产效率和生产资源配置的演化过程及区域对比特征。最后,有针对性地提出了促进我国玉米生产资源有效配置、提高玉米生产效率的相应措施与途径。%Maize production is affected by the restrictions and lots of inputs , such as seed seedlings, Labour, land, pesti-cide , chemical fertilizer , agricultural film , machinery and equipment , animal and other material input , improve the effi-ciency of input-output level of these factors is very important to promote efficient continuous corn production .Based on corn production cost compared with the yield time series in China and the United States , on the basis of the nonparamet-ric frontier efficiency based on DEA decomposition methods for main parts of the country's corn crop total factor produc-tivity question has carried on the empirical analysis , from the perspective of two different regions of the horizontal and vertical time sequence to study the evolution of China's corn production efficiency and resource allocation process and re-gional correlation characteristics .Finally , puts forward the promotion our country maize production resources effectively configuration , corresponding measures and way to improve efficiency of corn production .

  12. Parametric versus non-parametric simulation

    OpenAIRE

    Dupeux, Bérénice; Buysse, Jeroen

    2014-01-01

    Most of ex-ante impact assessment policy models have been based on a parametric approach. We develop a novel non-parametric approach, called Inverse DEA. We use non parametric efficiency analysis for determining the farm’s technology and behaviour. Then, we compare the parametric approach and the Inverse DEA models to a known data generating process. We use a bio-economic model as a data generating process reflecting a real world situation where often non-linear relationships exist. Results s...

  13. Molecular analysis and test of linkage between the FMR-I gene and infantile autism in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Hallmayer, J.; Pintado, E.; Lotspeich, L.; Spiker, D.; Kraemer, H.C.; Lee Wong, D.; Lin, A.; Herbert, J.; Cavalli-Sforza, L.L.; Ciaranello, R.D. [Stanford Univ., CA (United States)] [and others

    1994-11-01

    Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1. Further, because the overall lod scores for all probes in all models tested were highly negative, linkage to FMR-1 can also be ruled out in multiplex autistic families. 35 refs., 2 figs., 5 tabs.

  14. Candidate region linkage analysis in twins discordant or concordant for depression symptomatology

    DEFF Research Database (Denmark)

    Christiansen, Lene; Tan, Q; Kruse, T A

    2009-01-01

    Genetic risk factors contribute considerably to both clinical affective disorders and subsyndromal mood level. There is moreover evidence to suggest that the genetic basis of bipolar disorder and unipolar depression overlap to some extent, and several linkage analyses have suggested evidence...... for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected...

  15. Linkage analyses in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases.

    Science.gov (United States)

    Buhler, J; Owerbach, D; Schäffer, A A; Kimmel, M; Gabbay, K H

    1997-01-01

    We have developed software and statistical tools for linkage analysis of polygenic diseases. We use type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) as our model system. Two susceptibility loci (IDDM1 on 6p21 and IDDM2 on 11p15) are well established, and recent genome searches suggest the existence of other susceptibility loci. We have implemented CASPAR, a software tool that makes it possible to test for linkage quickly and efficiently using multiple polymorphic DNA markers simultaneously in nuclear families consisting of two unaffected parents and a pair of affected siblings (ASP). We use a simulation-based method to determine whether lod scores from a collection of ASP tests are significant. We test our new software and statistical tools to assess linkage of IDDM5 and IDDM7 conditioned on analyses with 1 or 2 other unlinked type I diabetes susceptibility loci. The results from the CASPAR analysis suggest that conditioning of IDDM5 on IDDM1 and IDDM4, and of IDDM7 on IDDM1 and IDDM2 provides significant benefits for the genetic analysis of polygenic loci.

  16. Nonparametric Inference for Periodic Sequences

    KAUST Repository

    Sun, Ying

    2012-02-01

    This article proposes a nonparametric method for estimating the period and values of a periodic sequence when the data are evenly spaced in time. The period is estimated by a "leave-out-one-cycle" version of cross-validation (CV) and complements the periodogram, a widely used tool for period estimation. The CV method is computationally simple and implicitly penalizes multiples of the smallest period, leading to a "virtually" consistent estimator of integer periods. This estimator is investigated both theoretically and by simulation.We also propose a nonparametric test of the null hypothesis that the data have constantmean against the alternative that the sequence of means is periodic. Finally, our methodology is demonstrated on three well-known time series: the sunspots and lynx trapping data, and the El Niño series of sea surface temperatures. © 2012 American Statistical Association and the American Society for Quality.

  17. Nonparametric Econometrics: The np Package

    Directory of Open Access Journals (Sweden)

    Tristen Hayfield

    2008-07-01

    Full Text Available We describe the R np package via a series of applications that may be of interest to applied econometricians. The np package implements a variety of nonparametric and semiparametric kernel-based estimators that are popular among econometricians. There are also procedures for nonparametric tests of significance and consistent model specification tests for parametric mean regression models and parametric quantile regression models, among others. The np package focuses on kernel methods appropriate for the mix of continuous, discrete, and categorical data often found in applied settings. Data-driven methods of bandwidth selection are emphasized throughout, though we caution the user that data-driven bandwidth selection methods can be computationally demanding.

  18. Astronomical Methods for Nonparametric Regression

    Science.gov (United States)

    Steinhardt, Charles L.; Jermyn, Adam

    2017-01-01

    I will discuss commonly used techniques for nonparametric regression in astronomy. We find that several of them, particularly running averages and running medians, are generically biased, asymmetric between dependent and independent variables, and perform poorly in recovering the underlying function, even when errors are present only in one variable. We then examine less-commonly used techniques such as Multivariate Adaptive Regressive Splines and Boosted Trees and find them superior in bias, asymmetry, and variance both theoretically and in practice under a wide range of numerical benchmarks. In this context the chief advantage of the common techniques is runtime, which even for large datasets is now measured in microseconds compared with milliseconds for the more statistically robust techniques. This points to a tradeoff between bias, variance, and computational resources which in recent years has shifted heavily in favor of the more advanced methods, primarily driven by Moore's Law. Along these lines, we also propose a new algorithm which has better overall statistical properties than all techniques examined thus far, at the cost of significantly worse runtime, in addition to providing guidance on choosing the nonparametric regression technique most suitable to any specific problem. We then examine the more general problem of errors in both variables and provide a new algorithm which performs well in most cases and lacks the clear asymmetry of existing non-parametric methods, which fail to account for errors in both variables.

  19. Genetic Linkage Analysis of the Natural Colored Fiber and Fuzzless Traits in Cotton

    Institute of Scientific and Technical Information of China (English)

    LI Fu-zhen; QIU Xin-mian; WANG Ju-qin; LU Yan-tin; BAO Li-sheng

    2008-01-01

    @@ Genetic linkage relationship of the natural colored fiber and six fuzzless seed germplasms in obsolete backgrounds of Gossypium hirsutum (AD genome) and G.barbadense were analyzed in the past two years.Three lines of natural brown fiber that were controlled by single dominant genes and two lines of green fiber controlled by another single dominant gene.

  20. QTL linkage analysis of connected populations using ancestral marker and pedigree information

    NARCIS (Netherlands)

    Bink, M.C.A.M.; Radu Totir, L.; Braak, ter C.J.F.; Winkler, C.R.; Boer, M.P.; Smith, O.S.

    2012-01-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the

  1. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius.

    Science.gov (United States)

    Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K

    2016-12-07

    The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. Copyright © 2016 Fountain et al.

  2. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

    Directory of Open Access Journals (Sweden)

    Toby Fountain

    2016-12-01

    Full Text Available The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG, with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species.

  3. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

    Science.gov (United States)

    Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K.

    2016-01-01

    The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. PMID:27733453

  4. QTL linkage analysis of connected populations using ancestral marker and pedigree information

    NARCIS (Netherlands)

    Bink, M.C.A.M.; Radu Totir, L.; Braak, ter C.J.F.; Winkler, C.R.; Boer, M.P.; Smith, O.S.

    2012-01-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the curr

  5. A Longitudinal Analysis of the Linkage between Suicide, Unemployment, and Marital Dissolution.

    Science.gov (United States)

    Wasserman, Ira M.

    1984-01-01

    Explores the linkage of divorce and suicide from 1964 to 1977, controlling for variations in unemployment. Findings demonstrated that, even with controls, the divorce rate explains variations in the suicide rate, suggesting that the kinship system is being greatly altered, which increases the propensity toward suicide. (JAC)

  6. FBN1 mutation in Chinese patients with Marfan syndrome and its gene diagnosis using haplotype linkage analysis

    Institute of Scientific and Technical Information of China (English)

    王冰; 胡冬煦; 夏家辉; 李崎; 杨进福; 吕国华

    2003-01-01

    Objectives To analyze the FBN1 mutations in Chinese patients with Marfan syndrome (MFS) and to make a genetic diagnosis based on haplotype linkage analysis for MFS. Methods Nine MFS families (17 patients) were analyzed with single strand conformation polymorphism (SSCP) and sequencing. Four primers were designed for the flanking sequences of FBN1 gene and used for haplotype-segregation analysis of MFS (B).Conclusion The combination of mutation detection and chromosome haplotype analysis can provide better evidence for a genetic diagnosis of MFS.

  7. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1.

    Science.gov (United States)

    Eggers, Stefanie; Smith, Katherine R; Bahlo, Melanie; Looijenga, Leendert H J; Drop, Stenvert L S; Juniarto, Zulfa A; Harley, Vincent R; Koopman, Peter; Faradz, Sultana M H; Sinclair, Andrew H

    2015-04-01

    Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. We used whole exome capture and massively parallel sequencing to analyse a large family with 46,XY DSD and 46,XX premature ovarian insufficiency. In addition, we used a recently developed method for linkage analysis using genotypes extracted from the MPS data. This approach identified a unique linkage peak on chromosome 9 and a novel, 3 bp, in-frame deletion in exon six of NR5A1 (steroidogenic factor-1 or SF1) in all affected individuals. We confirmed that the variant disrupts the SF1 protein and its ability to bind and regulate downstream genes. NR5A1 has key roles at multiple points in gonad development and steroidogenic pathways. The variant described here affects the function of SF1 in early testis development and later ovarian function, ultimately leading to the 46,XY DSD and 46,XX premature ovarian insufficiency phenotypes, respectively. This study shows that even at low coverage, whole exome sequencing, when combined with linkage analysis, can be a powerful tool to identify rapidly the disease-causing variant in large pedigrees.

  8. A Hierarchical Generalized Linear Model in Combination with Dispersion Modeling to Improve Sib-Pair Linkage Analysis.

    Science.gov (United States)

    Lee, Woojoo; Kim, Jeonghwan; Lee, Youngjo; Park, Taesung; Suh, Young Ju

    2015-01-01

    We explored a hierarchical generalized linear model (HGLM) in combination with dispersion modeling to improve the sib-pair linkage analysis based on the revised Haseman-Elston regression model for a quantitative trait. A dispersion modeling technique was investigated for sib-pair linkage analysis using simulation studies and real data applications. We considered 4 heterogeneous dispersion settings according to a signal-to-noise ratio (SNR) in the various statistical models based on the Haseman-Elston regression model. Our numerical studies demonstrated that susceptibility loci could be detected well by modeling the dispersion parameter appropriately. In particular, the HGLM had better performance than the linear regression model and the ordinary linear mixed model when the SNR is low, i.e., when substantial noise was present in the data. The study shows that the HGLM in combination with dispersion modeling can be utilized to identify multiple markers showing linkage to familial complex traits accurately. Appropriate dispersion modeling might be more powerful to identify markers closest to the major genes which determine a quantitative trait. © 2015 S. Karger AG, Basel.

  9. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  10. The phenotypic difference discards sib-pair QTL linkage information

    Energy Technology Data Exchange (ETDEWEB)

    Wright, F.A. [Univ. of California, San Diego, CA (United States)]|[Univ. of Texas, El Paso, TX (United States)

    1997-03-01

    Kruglyak and Lander provide an important synthesis of methods for (IBD) sib-pair linkage mapping, with an emphasis on the use of complete multipoint inheritance information for each sib pair. These procedures are implemented in the computer program MAPMAKER/SIBS, which performs interval mapping for dichotomous and quantitative traits. The authors present three methods for mapping quantitative trait loci (QTLs): a variant of the commonly used Haseman-Elston regression approach, a maximum-likelihood procedure involving variance components, and a rank-based nonparametric procedure. These approaches and related work use the magnitude of the difference in the sibling phenotype values for each sib pair as the observation for analysis. Linkage is detected if siblings sharing more alleles IBD have similar phenotypes (i.e., a small difference in the phenotype values), while siblings sharing fewer alleles IBD have less similar phenotypes. Such techniques have been used to detect linkage for a number of quantitative traits. However, the exclusive reliance on the phenotypic differences may be due in large part to historical inertia. A likelihood argument is presented here to show that, under certain classical assumptions, the phenotypic differences do not contain the full likelihood information for QTL mapping. Furthermore, considerable gains in power to detect linkage can be achieved with an expanded likelihood model. The development here is related to previous work, which incorporates the full set of phenotypic data using likelihood and robust quasi-likelihood methods. The purpose of this letter is not to endorse a particular approach but to spur research in alternative and perhaps more powerful linkage tests. 17 refs.

  11. DNA Marker Transmission and Linkage Analysis in Populations Derived from a Sugarcane (Saccharum spp. x Erianthus arundinaceus Hybrid.

    Directory of Open Access Journals (Sweden)

    Jian-wen Chen

    Full Text Available Introgression of Erianthus arundinaceus has been the focus of several sugarcane breeding programs in the world, because the species has desirable traits such as high biomass production, vigour, ratooning ability and good resistance to environmental stresses and disease. In this study four genetic maps were constructed for two intergeneric populations. The first population (BC1 was generated from a cross between an Erianthus/Saccharum hybrid YC96-40 and a commercial sugarcane variety CP84-1198. The second population (BC2 was generated from a cross between YCE01-116, a progeny of the BC1 cross and NJ57-416, a commercial sugarcane cultivar. Markers across both populations were generated using 35 AFLP and 23 SSR primer pairs. A total of 756 and 728 polymorphic markers were scored in the BC1 and BC2 populations, respectively. In the BC1 population, a higher proportion of markers was derived from the Erianthus ancestor than those from the Saccharum ancestor Badila. In the BC2 population, both the number and proportion of markers derived from Erianthus were approximately half of those in the BC1 population. Linkage analysis led to the construction of 38, 57, 36 and 47 linkage groups (LGs for YC96-40, CP84-1198, YCE01-116, and NJ57-416, encompassing 116, 174, 97 and 159 markers (including single dose, double dose and bi-parental markers, respectively. These LGs could be further placed into four, five, five and six homology groups (HGs, respectively, based on information from multi-allelic SSR markers and repulsion phase linkages detected between LGs. Analysis of repulsion phase linkage indicated that Erianthus behaved like a true autopolyploid.

  12. Comparing parametric and nonparametric regression methods for panel data

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    We investigate and compare the suitability of parametric and non-parametric stochastic regression methods for analysing production technologies and the optimal firm size. Our theoretical analysis shows that the most commonly used functional forms in empirical production analysis, Cobb......-Douglas and Translog, are unsuitable for analysing the optimal firm size. We show that the Translog functional form implies an implausible linear relationship between the (logarithmic) firm size and the elasticity of scale, where the slope is artificially related to the substitutability between the inputs....... The practical applicability of the parametric and non-parametric regression methods is scrutinised and compared by an empirical example: we analyse the production technology and investigate the optimal size of Polish crop farms based on a firm-level balanced panel data set. A nonparametric specification test...

  13. Quantitative Phylogenomics of Within-Species Mitogenome Variation: Monte Carlo and Non-Parametric Analysis of Phylogeographic Structure among Discrete Transatlantic Breeding Areas of Harp Seals (Pagophilus groenlandicus.

    Directory of Open Access Journals (Sweden)

    Steven M Carr

    -stepping-stone biogeographic models, but not a simple 1-step trans-Atlantic model. Plots of the cumulative pairwise sequence difference curves among seals in each of the four populations provide continuous proxies for phylogenetic diversification within each. Non-parametric Kolmogorov-Smirnov (K-S tests of maximum pairwise differences between these curves indicates that the Greenland Sea population has a markedly younger phylogenetic structure than either the White Sea population or the two Northwest Atlantic populations, which are of intermediate age and homogeneous structure. The Monte Carlo and K-S assessments provide sensitive quantitative tests of within-species mitogenomic phylogeography. This is the first study to indicate that the White Sea and Greenland Sea populations have different population genetic histories. The analysis supports the hypothesis that Harp Seals comprises three genetically distinguishable breeding populations, in the White Sea, Greenland Sea, and Northwest Atlantic. Implications for an ice-dependent species during ongoing climate change are discussed.

  14. 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.

  15. Exploring a Nonmodel Teleost Genome Through RAD Sequencing-Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis.

    Science.gov (United States)

    Manousaki, Tereza; Tsakogiannis, Alexandros; Taggart, John B; Palaiokostas, Christos; Tsaparis, Dimitris; Lagnel, Jacques; Chatziplis, Dimitrios; Magoulas, Antonios; Papandroulakis, Nikos; Mylonas, Constantinos C; Tsigenopoulos, Costas S

    2015-12-29

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax), Nile tilapia (Oreochromis niloticus), stickleback (Gasterosteus aculeatus), and medaka (Oryzias latipes), suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts.

  16. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    Directory of Open Access Journals (Sweden)

    Tereza Manousaki

    2016-03-01

    Full Text Available Common pandora (Pagellus erythrinus is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax, Nile tilapia (Oreochromis niloticus, stickleback (Gasterosteus aculeatus, and medaka (Oryzias latipes, suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts.

  17. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    Science.gov (United States)

    Manousaki, Tereza; Tsakogiannis, Alexandros; Taggart, John B.; Palaiokostas, Christos; Tsaparis, Dimitris; Lagnel, Jacques; Chatziplis, Dimitrios; Magoulas, Antonios; Papandroulakis, Nikos; Mylonas, Constantinos C.; Tsigenopoulos, Costas S.

    2015-01-01

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax), Nile tilapia (Oreochromis niloticus), stickleback (Gasterosteus aculeatus), and medaka (Oryzias latipes), suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts. PMID:26715088

  18. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers.

    Directory of Open Access Journals (Sweden)

    Minna K Karjalainen

    Full Text Available Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB. However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72 on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR and the interleukin-2 receptor gamma subunit (IL2RG, located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272 and their offspring (n = 269, and in mothers with exclusively term deliveries (n = 201 and their offspring (n = 199, all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111 and term (n = 197 from southern Finland was also analyzed. Long AR CAG repeats (≥ 26 were overrepresented and short repeats (≤ 19 underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

  19. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers.

    Science.gov (United States)

    Karjalainen, Minna K; Huusko, Johanna M; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J; Hallman, Mikko

    2012-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥ 26) were overrepresented and short repeats (≤ 19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

  20. Asymptotic theory of nonparametric regression estimates with censored data

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    For regression analysis, some useful information may have been lost when the responses are right censored. To estimate nonparametric functions, several estimates based on censored data have been proposed and their consistency and convergence rates have been studied in literature, but the optimal rates of global convergence have not been obtained yet. Because of the possible information loss, one may think that it is impossible for an estimate based on censored data to achieve the optimal rates of global convergence for nonparametric regression, which were established by Stone based on complete data. This paper constructs a regression spline estimate of a general nonparametric regression function based on right_censored response data, and proves, under some regularity conditions, that this estimate achieves the optimal rates of global convergence for nonparametric regression. Since the parameters for the nonparametric regression estimate have to be chosen based on a data driven criterion, we also obtain the asymptotic optimality of AIC, AICC, GCV, Cp and FPE criteria in the process of selecting the parameters.

  1. Rediscovery of Good-Turing estimators via Bayesian nonparametrics.

    Science.gov (United States)

    Favaro, Stefano; Nipoti, Bernardo; Teh, Yee Whye

    2016-03-01

    The problem of estimating discovery probabilities originated in the context of statistical ecology, and in recent years it has become popular due to its frequent appearance in challenging applications arising in genetics, bioinformatics, linguistics, designs of experiments, machine learning, etc. A full range of statistical approaches, parametric and nonparametric as well as frequentist and Bayesian, has been proposed for estimating discovery probabilities. In this article, we investigate the relationships between the celebrated Good-Turing approach, which is a frequentist nonparametric approach developed in the 1940s, and a Bayesian nonparametric approach recently introduced in the literature. Specifically, under the assumption of a two parameter Poisson-Dirichlet prior, we show that Bayesian nonparametric estimators of discovery probabilities are asymptotically equivalent, for a large sample size, to suitably smoothed Good-Turing estimators. As a by-product of this result, we introduce and investigate a methodology for deriving exact and asymptotic credible intervals to be associated with the Bayesian nonparametric estimators of discovery probabilities. The proposed methodology is illustrated through a comprehensive simulation study and the analysis of Expressed Sequence Tags data generated by sequencing a benchmark complementary DNA library.

  2. Linkage analysis of genes for resistance to downy mildew (Bremia lactucae) in lettuce (Lactuca sativa).

    Science.gov (United States)

    Hulbert, S H; Michelmore, R W

    1985-08-01

    The genetics of specific resistance was studied in F2 populations which segregated for either one or two resistance genes. The resistance factors 1, 11 and 14 which had not previously been characterized genetically segregated as single dominant genes (Dm). Resistance was determined by three linkage groups; R 1/14, 2, 3, and 6 in the first, R 5/8, and 10 in the second and R 4, 7 and 11 in the third. Cultivars of lettuce commonly used in the differential series to detect virulence to R3 and R10, were demonstrated to carry two tightly linked resistance genes. Implications of this linkage arrangement to the manipulation and characterization of these resistance genes are discussed.

  3. Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1996-07-01

    Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

  4. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Science.gov (United States)

    Wang, Jing; Zhang, Kaichun; Zhang, Xiaoming; Yan, Guohua; Zhou, Yu; Feng, Laibao; Ni, Yang; Duan, Xuwei

    2015-01-01

    A cross between the sweet cherry (Prunus avium) cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF) sequencing technique used as a single nucleotide polymorphism (SNP) discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs) and the incompatibility (S) gene, were used to build a map which comprised 8 linkage groups (LGs) and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD) is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding.

  5. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available A cross between the sweet cherry (Prunus avium cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF sequencing technique used as a single nucleotide polymorphism (SNP discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs and the incompatibility (S gene, were used to build a map which comprised 8 linkage groups (LGs and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding.

  6. A generalization of Kempe's linkages

    Institute of Scientific and Technical Information of China (English)

    MAO De-can; LUO Yao-zhi; YOU Zhong

    2007-01-01

    A new, general type of planar linkages is presented, which extends the classical linkages developed by Kempe consisting of two single-looped kinematic chains of linkages, interconnected by revolute hinges. Together with a locking device, these new linkages have only one degree of freedom (DOF), which makes them ideal for serving as deployable structures for different purposes. Here, we start with a fresh matrix method of analysis for double-loop planar linkages, using 2D transformation matrices and a new symbolic notation. Further inspection for one case of Kempe's linkages is provided. Basing on the inspection, by means of some novel algebraic and geometric techniques, one particularly fascinating solution was found. Physical models were built to show that the derivation in this paper is valid and the new mechanisms are correct.

  7. Nonparametric regression with filtered data

    CERN Document Server

    Linton, Oliver; Nielsen, Jens Perch; Van Keilegom, Ingrid; 10.3150/10-BEJ260

    2011-01-01

    We present a general principle for estimating a regression function nonparametrically, allowing for a wide variety of data filtering, for example, repeated left truncation and right censoring. Both the mean and the median regression cases are considered. The method works by first estimating the conditional hazard function or conditional survivor function and then integrating. We also investigate improved methods that take account of model structure such as independent errors and show that such methods can improve performance when the model structure is true. We establish the pointwise asymptotic normality of our estimators.

  8. Nonparametric identification of copula structures

    KAUST Repository

    Li, Bo

    2013-06-01

    We propose a unified framework for testing a variety of assumptions commonly made about the structure of copulas, including symmetry, radial symmetry, joint symmetry, associativity and Archimedeanity, and max-stability. Our test is nonparametric and based on the asymptotic distribution of the empirical copula process.We perform simulation experiments to evaluate our test and conclude that our method is reliable and powerful for assessing common assumptions on the structure of copulas, particularly when the sample size is moderately large. We illustrate our testing approach on two datasets. © 2013 American Statistical Association.

  9. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome).

    Science.gov (United States)

    Roberts, Aedan; Nancarrow, Derek; Clendenning, Mark; Buchanan, Daniel D; Jenkins, Mark A; Duggan, David; Taverna, Darin; McKeone, Diane; Walters, Rhiannon; Walsh, Michael D; Young, Bruce W; Jass, Jeremy R; Rosty, Christophe; Gattas, Michael; Pelzer, Elise; Hopper, John L; Goldblatt, Jack; George, Jill; Suthers, Graeme K; Phillips, Kerry; Parry, Susan; Woodall, Sonja; Arnold, Julie; Tucker, Kathy; Muir, Amanda; Drini, Musa; Macrae, Finlay; Newcomb, Polly; Potter, John D; Pavluk, Erika; Lindblom, Annika; Young, Joanne P

    2011-06-01

    Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

  10. Equity and efficiency in private and public education: a nonparametric comparison

    NARCIS (Netherlands)

    L. Cherchye; K. de Witte; E. Ooghe; I. Nicaise

    2007-01-01

    We present a nonparametric approach for the equity and efficiency evaluation of (private and public) primary schools in Flanders. First, we use a nonparametric (Data Envelopment Analysis) model that is specially tailored to assess educational efficiency at the pupil level. The model accounts for the

  11. Non-parametric tests of productive efficiency with errors-in-variables

    NARCIS (Netherlands)

    Kuosmanen, T.K.; Post, T.; Scholtes, S.

    2007-01-01

    We develop a non-parametric test of productive efficiency that accounts for errors-in-variables, following the approach of Varian. [1985. Nonparametric analysis of optimizing behavior with measurement error. Journal of Econometrics 30(1/2), 445-458]. The test is based on the general Pareto-Koopmans

  12. Equity and efficiency in private and public education: a nonparametric comparison

    NARCIS (Netherlands)

    Cherchye, L.; de Witte, K.; Ooghe, E.; Nicaise, I.

    2007-01-01

    We present a nonparametric approach for the equity and efficiency evaluation of (private and public) primary schools in Flanders. First, we use a nonparametric (Data Envelopment Analysis) model that is specially tailored to assess educational efficiency at the pupil level. The model accounts for the

  13. Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

    Science.gov (United States)

    Visscher, P M; Haley, C S; Ewald, H; Mors, O; Egeland, J; Thiel, B; Ginns, E; Muir, W; Blackwood, D H

    2005-02-05

    To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable. (c) 2004 Wiley-Liss, Inc.

  14. A contingency table approach to nonparametric testing

    CERN Document Server

    Rayner, JCW

    2000-01-01

    Most texts on nonparametric techniques concentrate on location and linear-linear (correlation) tests, with less emphasis on dispersion effects and linear-quadratic tests. Tests for higher moment effects are virtually ignored. Using a fresh approach, A Contingency Table Approach to Nonparametric Testing unifies and extends the popular, standard tests by linking them to tests based on models for data that can be presented in contingency tables.This approach unifies popular nonparametric statistical inference and makes the traditional, most commonly performed nonparametric analyses much more comp

  15. 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.

  16. Considerations in using linkage analysis as a presymptomatic test for Huntington's disease.

    Science.gov (United States)

    Farrer, L A; Myers, R H; Cupples, L A; Conneally, P M

    1988-09-01

    The polymorphic locus D4S10 that is genetically linked to the locus for Huntington's disease (HD) has made possible a presymptomatic test for those at risk. Because the symptoms of this progressively debilitating and fatal illness are not usually manifest until adulthood, the outcome of the test will influence major decisions about career, marriage, and procreation. Several differential diagnoses must be considered before using the test if HD is not confirmed in at least one family member. Review of a large number of pedigrees has shown that 40% of persons at risk do not have appropriate family structure for a linkage test. Furthermore, uncooperative or inaccessible relatives may make this test infeasible for many others who wish to be tested. Linkage phase, which must be known in the affected parent for an informative test, can be determined using one or more of 12 probe-enzyme combinations for D4S10. Although the polymorphism information content (PIC) value for any one RFLP is less than 40%, the PIC value for the haplotype of the two G8 HindIII, pK083 EcoRI, and R7 BglII RFLPs is greater than 88%. We have developed a scheme to incorporate linkage data and age at onset information adjusted for censored observations, sex of affected parent, and familial correlation for age at onset, using the computer program MLINK for calculation of risk of having HD. Simulated experiments showed that proper age at onset adjustment is crucial to the calculation of the probability of risk. A formal presymptomatic testing protocol, including pre- and post-test counselling, psychological testing, and paternity testing is recommended. Many of these considerations are illustrated in several actual test cases.

  17. Estimation of Spatial Dynamic Nonparametric Durbin Models with Fixed Effects

    Science.gov (United States)

    Qian, Minghui; Hu, Ridong; Chen, Jianwei

    2016-01-01

    Spatial panel data models have been widely studied and applied in both scientific and social science disciplines, especially in the analysis of spatial influence. In this paper, we consider the spatial dynamic nonparametric Durbin model (SDNDM) with fixed effects, which takes the nonlinear factors into account base on the spatial dynamic panel…

  18. Non-parametric Bayesian inference for inhomogeneous Markov point processes

    DEFF Research Database (Denmark)

    Berthelsen, Kasper Klitgaard; Møller, Jesper

    With reference to a specific data set, we consider how to perform a flexible non-parametric Bayesian analysis of an inhomogeneous point pattern modelled by a Markov point process, with a location dependent first order term and pairwise interaction only. A priori we assume that the first order term...

  19. Homothetic Efficiency and Test Power: A Non-Parametric Approach

    NARCIS (Netherlands)

    J. Heufer (Jan); P. Hjertstrand (Per)

    2015-01-01

    markdownabstract__Abstract__ We provide a nonparametric revealed preference approach to demand analysis based on homothetic efficiency. Homotheticity is a useful restriction but data rarely satisfies testable conditions. To overcome this we provide a way to estimate homothetic efficiency of consump

  20. Water quality analysis in rivers with non-parametric probability distributions and fuzzy inference systems: application to the Cauca River, Colombia.

    Science.gov (United States)

    Ocampo-Duque, William; Osorio, Carolina; Piamba, Christian; Schuhmacher, Marta; Domingo, José L

    2013-02-01

    The integration of water quality monitoring variables is essential in environmental decision making. Nowadays, advanced techniques to manage subjectivity, imprecision, uncertainty, vagueness, and variability are required in such complex evaluation process. We here propose a probabilistic fuzzy hybrid model to assess river water quality. Fuzzy logic reasoning has been used to compute a water quality integrative index. By applying a Monte Carlo technique, based on non-parametric probability distributions, the randomness of model inputs was estimated. Annual histograms of nine water quality variables were built with monitoring data systematically collected in the Colombian Cauca River, and probability density estimations using the kernel smoothing method were applied to fit data. Several years were assessed, and river sectors upstream and downstream the city of Santiago de Cali, a big city with basic wastewater treatment and high industrial activity, were analyzed. The probabilistic fuzzy water quality index was able to explain the reduction in water quality, as the river receives a larger number of agriculture, domestic, and industrial effluents. The results of the hybrid model were compared to traditional water quality indexes. The main advantage of the proposed method is that it considers flexible boundaries between the linguistic qualifiers used to define the water status, being the belongingness of water quality to the diverse output fuzzy sets or classes provided with percentiles and histograms, which allows classify better the real water condition. The results of this study show that fuzzy inference systems integrated to stochastic non-parametric techniques may be used as complementary tools in water quality indexing methodologies.

  1. Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.

    Science.gov (United States)

    Ptacek, L J; Tyler, F; Trimmer, J S; Agnew, W S; Leppert, M

    1991-01-01

    Hyperkalemic periodic paralysis (HYPP) is an autosomal dominant muscle disease with electrophysiological abnormalities suggesting a defect in a voltage-gated sodium channel (NaCh) gene. A human NaCh gene was recently shown to cosegregate with the disease allele in a family with HYPP. Using an independent clone, we have demonstrated close genetic linkage between an NaCh gene and the HYPP locus in another family. With physiological data demonstrating abnormal NaCh function in HYPP patients, the absence of any obligate recombinations in the two families strengthens the argument that this NaCh gene is the site of the defect in this disorder. PMID:1651050

  2. Linkage Map Construction and Quantitative Trait Loci Analysis for Bolting Based on a Double Haploid Population of Brassica rapa

    Institute of Scientific and Technical Information of China (English)

    Xu Yang; Yang-Jun Yu; Feng-Lan Zhang; Zhi-Rong Zou; Xiu-Yun Zhao; De-Shuang Zhang; Jia-Bing Xu

    2007-01-01

    Early bolting of Chinese cabbage (Brassica rapa L.) during spring cultivation often has detrimental effects on the yield and quality of the harvested products. Breeding late bolting varieties is a major objective of Chinese cabbage breeding programs. in order to analyze the genetic basis of bolting traits, a genetic map of B. rapa was constructed based on amplified fragment-length polymorphism (AFLP), sequence-related amplified polymorphism (SRAP), simple sequence repeat (SSR), random amplification of polymorphic DNA (RAPD), and isozyme markers. Marker analysis was carried out on 81 double haploid (DH) lines obtained by mlcrospore culture from F1 progeny of two homozygous parents: B. rapa L. ssp. pekinensis (BY) (an extra-early bolting Chinese cabbage line) and B. rapa L. ssp. rapifera (MM) (an extra-late bolting European turnip line). A total of 326 markers including 130 AFLPs, 123 SRAPs, 16 SSRs, 43RAPDs and 14 isozymes were used to construct a linkage map with 10 linkage groups covering 882 cM with an average distance of 2.71 cM between loci. The bolting trait of each DH line was evaluated by the bolting index under controlled conditions. Quantitative trait loci (QTL) analysis was conducted using multiple QTL model mapping with MapQTL5.0 software. Eight QTLs controlling bolting resistance were identified. These QTLs, accounting for 14.1% to 25.2% of the phenotyplc variation with positive additive effects, were distributed into three linkage groups. These results provide useful information for molecular marker-assisted selection of late bolting traits in Chinese cabbage breeding programs.

  3. Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Lynch, E.D.; Golbus, M.S. (Univ. of California, San Francisco (United States)); Bird, T.D. (Univ. of Washington, Seattle (United States)); Barker, D.F.; O' Connell, P.; Chance, P.F. (Univ. of Utah, Salt Lake City (United States))

    1992-01-01

    This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers. Additional loci were physically mapped and ordered by in situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.

  4. Examination of X chromosome markers in Rett syndrome: Exclusion mapping with a novel variation on multilocus linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, K.A.; Fill, C.P. (Baylor College of Medicine, Houston, TX (United States)); Terwililger, J.; Percy, A.K.; Zobhbi, H. (Columbia University, NY (United States)); DeGennaro, L.J.; Ott, J. (University of Massachusetts Medical School, Worcester (United States)); Anvret, M.; Martin-Gallardo, A. (National Institutes of Health, Bethesda, MD (United States))

    1992-02-01

    Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and sterotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than [minus]2, the authors were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed.

  5. Improving linkage analysis in outcrossed forest trees - an example from Acacia mangium.

    Science.gov (United States)

    Butcher, A.; Williams, R.; Whitaker, D.; Ling, S.; Speed, P.; Moran, F.

    2002-05-01

    Mapping in forest trees generally relies on outbred pedigrees in which genetic segregation is the result of meiotic recombination from both parents. The currently available mapping packages are not optimal for outcrossed pedigrees as they either cannot order phase-ambiguous data or only use pairwise information when ordering loci within linkage groups. A new package, OUTMAP, has been developed for mapping codominant loci in outcrossed trees. A comparison of maps produced using linkage data from two pedigrees of Acacia mangium Willd demonstrated that the marker orders produced using OUTMAP were consistently of higher likelihood than those produced by JOINMAP. In addition, the maps were produced more efficiently, without the need for recoding data or the detailed investigation of pairwise recombination fractions which was necessary to select the optimal marker order using JOINMAP. Distances between markers often varied from those calculated by JOINMAP, resulting in an increase in the estimated genome length. OUTMAP can be used with all segregation types to determine phase and to calculate the likelihood of alternative marker orders, with a choice of three optimisation methods.

  6. Nonparametric Regression with Common Shocks

    Directory of Open Access Journals (Sweden)

    Eduardo A. Souza-Rodrigues

    2016-09-01

    Full Text Available This paper considers a nonparametric regression model for cross-sectional data in the presence of common shocks. Common shocks are allowed to be very general in nature; they do not need to be finite dimensional with a known (small number of factors. I investigate the properties of the Nadaraya-Watson kernel estimator and determine how general the common shocks can be while still obtaining meaningful kernel estimates. Restrictions on the common shocks are necessary because kernel estimators typically manipulate conditional densities, and conditional densities do not necessarily exist in the present case. By appealing to disintegration theory, I provide sufficient conditions for the existence of such conditional densities and show that the estimator converges in probability to the Kolmogorov conditional expectation given the sigma-field generated by the common shocks. I also establish the rate of convergence and the asymptotic distribution of the kernel estimator.

  7. 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....

  8. An asymptotically optimal nonparametric adaptive controller

    Institute of Scientific and Technical Information of China (English)

    郭雷; 谢亮亮

    2000-01-01

    For discrete-time nonlinear stochastic systems with unknown nonparametric structure, a kernel estimation-based nonparametric adaptive controller is constructed based on truncated certainty equivalence principle. Global stability and asymptotic optimality of the closed-loop systems are established without resorting to any external excitations.

  9. Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Kimiyo Kikuchi

    Full Text Available Continuum of care has the potential to improve maternal, newborn, and child health (MNCH by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood and space dimensions (from community-family care to clinical care. However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries.We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers' uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality.Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%. Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%.Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the

  10. Cointegration and causality analysis of dynamic linkage between stock market and equity mutual funds in Australia

    Directory of Open Access Journals (Sweden)

    Sasipa Pojanavatee

    2014-12-01

    Full Text Available The existing literature finds conflicting results on the magnitude of price linkages between equity mutual funds and the stock market. The study contends that in an optimal lagged model, the expectations of future prices using knowledge of past price behaviour in a particular equity mutual fund category will improve forecasts of prices of other equity mutual fund categories and the stock market index. The evidence shows that the long-run pricing of equity mutual funds is cointegrated with the stock market index. In the short run, the results indicate that some equity mutual fund categories possess both long-run and short-run exogeneity with the stock market. Therefore, the short-run dynamic indicates short-run Granger causal links running between different equity mutual fund categories.

  11. A genome-wide linkage analysis for the personality trait neuroticism in the Irish affected sib-pair study of alcohol dependence.

    Science.gov (United States)

    Kuo, Po-Hsiu; Neale, Michael C; Riley, Brien P; Patterson, Diana G; Walsh, Dermot; Prescott, Carol A; Kendler, Kenneth S

    2007-06-05

    Neuroticism is a personality trait which reflects individual differences in emotional stability and vulnerability to stress and anxiety. Consistent evidence shows substantial genetic influences on variation in this trait. The present study seeks to identify regions containing susceptibility loci for neuroticism using a selected sib-pair sample from Ireland. Using Merlin regress, we conducted a 4 cM whole-genome linkage analysis on 714 sib-pairs. Evidence for linkage to neuroticism was found on chromosomes 11p, 12q, and 15q. The highest linkage peak was on 12q at marker D12S1638 with a Lod score of 2.13 (-log p = 2.76, empirical P-value neuroticism, with male specific linkage regions on chromosomes 1, 4, 11, 12, 15, 16, and 22, and female specific linkage regions on chromosomes 2, 4, 9, 12, 13, and 18. Some genome regions reported in the present study replicate findings from previous linkage studies of neuroticism. These results, together with prior studies, indicate several potential regions for quantitative trait loci for neuroticism that warrant further study.

  12. Identification of a candidate gene for panicle length in rice (Oryza sativa L. via association and linkage analysis

    Directory of Open Access Journals (Sweden)

    Erbao eLiu

    2016-05-01

    Full Text Available Panicle length (PL is an important trait for improving panicle architecture and grain yield in rice (Oryza sativa L.. Three populations were used to identify QTLs and candidate genes associated with PL. Four QTLs for PL were detected on chromosomes 4, 6 and 9 through linkage mapping in the recombinant inbred line population derived from a cross between the cultivars Xiushui79 (short panicle and C-bao (long panicle. Ten SSR markers associated with PL were detected on chromosomes 2, 3, 5, 6, 8, 9 and 10 in the natural population consisting of 540 accessions collected from East and Southeast Asia. A major locus on chromosome 9 with the largest effect was identified via both linkage and association mapping. LONG PANICLE 1 (LP1 locus was delimited to a 90-kb region of the long arm of chromosome 9 through fine mapping using a single segment segregating F2 population. Two single nucleotide polymorphisms (SNPs leading to amino acid changes were detected in the third and fifth exons of LP1. LP1encodes a Remorin_C-containing protein of unknown function with homologs in a variety of species. Sequencing analysis of LP1 in two parents and 103 rice accessions indicated that SNP1 is associated with panicle length. The LP1 allele of Xiushui79 leads to reduced panicle length, whereas the allele of C-bao relieves the suppression of panicle length. LP1 and the elite alleles can be used to improve panicle length in rice.

  13. Construction of a linkage map and QTL analysis of horticultural traits for watermelon [Citrullus lanatus (THUNB.) MATSUM & NAKAI] using RAPD, RFLP and ISSR markers.

    Science.gov (United States)

    Hashizume, T; Shimamoto, I; Hirai, M

    2003-03-01

    We have been constructing linkage maps for watermelon ( Citrullus lanatus) on the basis of random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), inter-simple sequence repeats (ISSRs) and isozymes using an F(2) population derived from a crossing between a cultivated inbred line (H-7; C. lanatus) and an African wild form (SA-1; C. lanatus). A total of 120 F(2) plants was used for construction of a linkage map using 477 RAPDs, 53 RFLPs, 23 ISSRs and one isozyme markers. Linkage analysis revealed that 554 loci could be mapped to 11 linkage groups that extended for 2,384 centimorgans (cM). While a BC(1) population [(H-7 x SA-1) x H-7] consisting of 60 individuals was grown and scored for quantitative traits. Another linkage map with a total length of 1,729 cM was constructed in the BC(1) using genetic markers found to segregate in the F(2) population. A QTL analysis was applied by means of interval mapping for locating such agronomic traits as hardness of rind, Brix of flesh juice, flesh color (red and yellow) and rind color. The relative order of markers in the BC(1) map was essentially the same as that on the linkage map in the F(2). A total of five QTLs for four agronomic traits was detected. The QTL for hardness of rind was mapped on group 4. The linkage group 8 contained the QTL for sugar content of the flesh as expressed in Brix of the juice. The QTL for red flesh color was detected on groups 2 and 8. The QTL for rind color mapped on the group 3. The present map and QTL analysis may provide a useful tool for breeders by introducing valuable wild watermelon genes to cultivars.

  14. Genomewide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p

    Science.gov (United States)

    Arinami, Tadao; Ohtsuki, Tsuyuka; Ishiguro, Hiroki; Ujike, Hiroshi; Tanaka, Yuji; Morita, Yukitaka; Mineta, Mari; Takeichi, Masashi; Yamada, Shigeto; Imamura, Akira; Ohara, Koichi; Shibuya, Haruo; Ohara, Kenshiro; Suzuki, Yasuo; Muratake, Tatsuyuki; Kaneko, Naoshi; Someya, Toshiyuki; Inada, Toshiya; Yoshikawa, Takeo; Toyota, Tomoko; Yamada, Kazuo; Kojima, Takuya; Takahashi, Sakae; Osamu, Ohmori; Shinkai, Takahiro; Nakamura, Michiko; Fukuzako, Hiroshi; Hashiguchi, Tomo; Niwa, Shin-ich; Ueno, Takuya; Tachikawa, Hirokazu; Hori, Takafumi; Asada, Takashi; Nanko, Shinichiro; Kunugi, Hiroshi; Hashimoto, Ryota; Ozaki, Norio; Iwata, Nakao; Harano, Mutsuo; Arai, Heii; Ohnuma, Tohru; Kusumi, Ichiro; Koyama, Tsukasa; Yoneda, Hiroshi; Fukumaki, Yasuyuki; Shibata, Hiroki; Kaneko, Sunao; Higuchi, Hisashi; Yasui-Furukori, Norio; Numachi, Yohtaro; Itokawa, Masanari; Okazaki, Yuji

    2005-01-01

    The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects. PMID:16380906

  15. SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss (DFNA15.

    Directory of Open Access Journals (Sweden)

    Hee-Jin Kim

    Full Text Available Autosomal dominant non-syndromic hearing loss (AD-NSHL is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15 described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3(rd alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL.

  16. A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.

    Science.gov (United States)

    Clément, K; Dina, C; Basdevant, A; Chastang, N; Pelloux, V; Lahlou, N; Berlan, M; Langin, D; Guy-Grand, B; Froguel, P

    1999-02-01

    As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.

  17. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    Science.gov (United States)

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  18. Linkage studies of bipolar disorder with chromosome 18 markers.

    Science.gov (United States)

    Bowen, T; Kirov, G; Gill, M; Spurlock, G; Vallada, H P; Murray, R M; McGuffin, P; Collier, D A; Owen, M J; Craddock, N

    1999-10-15

    Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.

  19. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    Science.gov (United States)

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  20. 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.

  1. A Novel Method to Magnetic Flux Linkage Optimization of Direct-Driven Surface-Mounted Permanent Magnet Synchronous Generator Based on Nonlinear Dynamic Analysis

    Directory of Open Access Journals (Sweden)

    Qian Xie

    2016-07-01

    Full Text Available This paper pays attention to magnetic flux linkage optimization of a direct-driven surface-mounted permanent magnet synchronous generator (D-SPMSG. A new compact representation of the D-SPMSG nonlinear dynamic differential equations to reduce system parameters is established. Furthermore, the nonlinear dynamic characteristics of new D-SPMSG equations in the process of varying magnetic flux linkage are considered, which are illustrated by Lyapunov exponent spectrums, phase orbits, Poincaré maps, time waveforms and bifurcation diagrams, and the magnetic flux linkage stable region of D-SPMSG is acquired concurrently. Based on the above modeling and analyses, a novel method of magnetic flux linkage optimization is presented. In addition, a 2 MW D-SPMSG 2D/3D model is designed by ANSYS software according to the practical design requirements. Finally, five cases of D-SPMSG models with different magnetic flux linkages are simulated by using the finite element analysis (FEA method. The nephograms of magnetic flux density are agreement with theoretical analysis, which both confirm the correctness and effectiveness of the proposed approach.

  2. Nonparametric methods in actigraphy: An update

    Directory of Open Access Journals (Sweden)

    Bruno S.B. Gonçalves

    2014-09-01

    Full Text Available Circadian rhythmicity in humans has been well studied using actigraphy, a method of measuring gross motor movement. As actigraphic technology continues to evolve, it is important for data analysis to keep pace with new variables and features. Our objective is to study the behavior of two variables, interdaily stability and intradaily variability, to describe rest activity rhythm. Simulated data and actigraphy data of humans, rats, and marmosets were used in this study. We modified the method of calculation for IV and IS by modifying the time intervals of analysis. For each variable, we calculated the average value (IVm and ISm results for each time interval. Simulated data showed that (1 synchronization analysis depends on sample size, and (2 fragmentation is independent of the amplitude of the generated noise. We were able to obtain a significant difference in the fragmentation patterns of stroke patients using an IVm variable, while the variable IV60 was not identified. Rhythmic synchronization of activity and rest was significantly higher in young than adults with Parkinson׳s when using the ISM variable; however, this difference was not seen using IS60. We propose an updated format to calculate rhythmic fragmentation, including two additional optional variables. These alternative methods of nonparametric analysis aim to more precisely detect sleep–wake cycle fragmentation and synchronization.

  3. Nonparametric methods in actigraphy: An update

    Science.gov (United States)

    Gonçalves, Bruno S.B.; Cavalcanti, Paula R.A.; Tavares, Gracilene R.; Campos, Tania F.; Araujo, John F.

    2014-01-01

    Circadian rhythmicity in humans has been well studied using actigraphy, a method of measuring gross motor movement. As actigraphic technology continues to evolve, it is important for data analysis to keep pace with new variables and features. Our objective is to study the behavior of two variables, interdaily stability and intradaily variability, to describe rest activity rhythm. Simulated data and actigraphy data of humans, rats, and marmosets were used in this study. We modified the method of calculation for IV and IS by modifying the time intervals of analysis. For each variable, we calculated the average value (IVm and ISm) results for each time interval. Simulated data showed that (1) synchronization analysis depends on sample size, and (2) fragmentation is independent of the amplitude of the generated noise. We were able to obtain a significant difference in the fragmentation patterns of stroke patients using an IVm variable, while the variable IV60 was not identified. Rhythmic synchronization of activity and rest was significantly higher in young than adults with Parkinson׳s when using the ISM variable; however, this difference was not seen using IS60. We propose an updated format to calculate rhythmic fragmentation, including two additional optional variables. These alternative methods of nonparametric analysis aim to more precisely detect sleep–wake cycle fragmentation and synchronization. PMID:26483921

  4. Analysis of biomarkers for the cross-linkage of formaldehyde with bovine serum albumin peptides

    Institute of Scientific and Technical Information of China (English)

    AHMAD Waqar; DENG YuLin; LI Bo; LI LiLi; AHAMD Manzoor; IQBAL Zafar; PARVEEN Zahida

    2008-01-01

    Formaldehyde, a well-known environmental toxic hazard, has been found to produce endogenously via semicarbazide-sensitive amine oxidase-catalyzed oxidative deamination of methylamine. In diabetes,the activity of SSAO has been found to increase with a subsequent increase in endogenous formalde-hyde production. It has been postulated that SSAO-induced production of formaldehyde may be in-volved in the alteration of protein structure, which may subsequently cause protein deposition associ-ated with chronic pathological disorders. Formaldehyde has also been found to react (cross-link) withamino group of the N-terminal amino acid residue and with the side-chains of arginine, cysteine, his-tidine and lysine residues. Therefore, formaldehyde may be responsible, at least in part, for protein cross-linkage, oxidative stress and cytotoxicity. The cross-linking of formaldehyde with bovine serum albumin was studied using LC-MS and Mascot database. The peptides sequence for control BSA (un-treated) digested with trypsin was matched in the online database search query by exporting the MS/MS data to online MASCOT database. In this way, a total of twenty-seven peptides were matched in the database search query. These twenty-seven peptides were then searched manually in all of the tryptic BSA samples treated with different concentrations of FA that were incubated in different time intervals.Six formaldehyde-treated BSA peptides (FKDLGEEHFK, HLVDEPQNLIK, KVPQVSTPTLVEVSR,RPCFSALTPDETYVPK, LVNELTEFAK, DAFLGSFLYEYSR) were found to be the possible markers for formaldehyde-protein/peptides adducts.

  5. Parametric and Non-Parametric System Modelling

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg

    1999-01-01

    considered. It is shown that adaptive estimation in conditional parametric models can be performed by combining the well known methods of local polynomial regression and recursive least squares with exponential forgetting. The approach used for estimation in conditional parametric models also highlights how....... For this purpose non-parametric methods together with additive models are suggested. Also, a new approach specifically designed to detect non-linearities is introduced. Confidence intervals are constructed by use of bootstrapping. As a link between non-parametric and parametric methods a paper dealing with neural...... the focus is on combinations of parametric and non-parametric methods of regression. This combination can be in terms of additive models where e.g. one or more non-parametric term is added to a linear regression model. It can also be in terms of conditional parametric models where the coefficients...

  6. Bayesian nonparametric duration model with censorship

    Directory of Open Access Journals (Sweden)

    Joseph Hakizamungu

    2007-10-01

    Full Text Available This paper is concerned with nonparametric i.i.d. durations models censored observations and we establish by a simple and unified approach the general structure of a bayesian nonparametric estimator for a survival function S. For Dirichlet prior distributions, we describe completely the structure of the posterior distribution of the survival function. These results are essentially supported by prior and posterior independence properties.

  7. Bootstrap Estimation for Nonparametric Efficiency Estimates

    OpenAIRE

    1995-01-01

    This paper develops a consistent bootstrap estimation procedure to obtain confidence intervals for nonparametric measures of productive efficiency. Although the methodology is illustrated in terms of technical efficiency measured by output distance functions, the technique can be easily extended to other consistent nonparametric frontier models. Variation in estimated efficiency scores is assumed to result from variation in empirical approximations to the true boundary of the production set. ...

  8. 偏执型与未分化型精神分裂症家系两个靶染色体易感位点的连锁分析%Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia

    Institute of Scientific and Technical Information of China (English)

    曾丽苹; 龙志高; 戴和平; 张灼华; 夏家辉; 赵靖平; 夏昆; 胡正茂; 穆莉莉; 梅桂森; 路秀玲; 郑永军; 李培建; 张瑛雪; 潘乾

    2011-01-01

    were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-Ⅳ-TR; American Psychiatric Association, 2000). All subjects signed informed consent. Results In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α=0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P=0.0367) at D1S484. The single point NPL score was 1.95 (P=0.0145) and the multi-point NPL score was 2.39 (P=0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P=0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α=0.40) and the multi-point HLOD was 1.12 (α=0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL

  9. Linkage disequilibrium and population-structure analysis among Capsicum annuum L. cultivars for use in association mapping.

    Science.gov (United States)

    Nimmakayala, Padma; Abburi, Venkata L; Abburi, Lavanya; Alaparthi, Suresh Babu; Cantrell, Robert; Park, Minkyu; Choi, Doil; Hankins, Gerald; Malkaram, Sridhar; Reddy, Umesh K

    2014-08-01

    Knowledge of population structure and linkage disequilibrium among the worldwide collections of peppers currently classified as hot, mild, sweet and ornamental types is indispensable for applying association mapping and genomic selection to improve pepper. The current study aimed to resolve the genetic diversity and relatedness of Capsicum annuum germplasm by use of simple sequence repeat (SSR) loci across all chromosomes in samples collected in 2011 and 2012. The physical distance covered by the entire set of SSRs used was 2,265.9 Mb from the 3.48-Gb hot-pepper genome size. The model-based program STRUCTURE was used to infer five clusters, which was further confirmed by classical molecular-genetic diversity analysis. Mean heterozygosity of various loci was estimated to be 0.15. Linkage disequilibrium (LD) was used to identify 17 LD blocks across various chromosomes with sizes from 0.154 Kb to 126.28 Mb. CAMS-142 of chromosome 1 was significantly associated with both capsaicin (CA) and dihydrocapsaicin (DCA) levels. Further, CAMS-142 was located in an LD block of 98.18 Mb. CAMS-142 amplified bands of 244, 268, 283 and 326 bp. Alleles 268 and 283 bp had positive effects on both CA and DCA levels, with an average R(2) of 12.15 % (CA) and 12.3 % (DCA). Eight markers from seven different chromosomes were significantly associated with fruit weight, contributing an average effect of 15 %. CAMS-199, HpmsE082 and CAMS-190 are the three major quantitative trait loci located on chromosomes 8, 9, and 10, respectively, and were associated with fruit weight in samples from both years of the study. This research demonstrates the effectiveness of using genome-wide SSR-based markers to assess features of LD and genetic diversity within C. annuum.

  10. Linkage Maps of a Mediterranean × Continental Tall Fescue Population and their Comparative Analysis with Other Poaceae Species

    Directory of Open Access Journals (Sweden)

    Ryan Dierking

    2015-03-01

    Full Text Available Temperate grasses belonging to the complex are important throughout the world in pasture and grassland agriculture. Tall fescue ( Schreb. is the predominant species in the United States, covering approximately 15 million ha. Tall fescue has distinctive morphotypes, two of which are Continental (summer active and Mediterranean (summer semidormant. This is the first report of a linkage map created for Mediterranean tall fescue, while updating the Continental map with additional simple sequence repeat and sequence-tagged site markers. Additionally, this is the first time that diversity arrays technology (DArT markers were used in the construction of a tall fescue map. The male parent (Continental, R43-64, map consisted of 594 markers arranged in 22 linkage groups (LGs and covered a total of 1577 cM. The female parent (Mediterranean, 103-2, map was shorter (1258 cM and consisted of only 208 markers arranged in 29 LGs. Marker densities for R43-64 and 103-2 were 2.65 and 6.08 cM per marker, respectively. When compared with the other Poaceae species, meadow fescue ( Huds., annual ryegrass ( Lam., perennial ryegrass ( L., (L. Beauv., and barley ( L., a total of 171 and 98 orthologous or homologous sequences, identified by DArT analysis, were identified in R43-64 and 103-2, respectively. By using genomic in situ hybridization, we aimed to identify potential progenitors of both morphotypes. However, no clear conclusion on genomic constitution was reached. These maps will aid in the search for quantitative trait loci of various traits as well as help define and distinguish genetic differences between the two morphotypes.

  11. Nonparametric estimation for hazard rate monotonously decreasing system

    Institute of Scientific and Technical Information of China (English)

    Han Fengyan; Li Weisong

    2005-01-01

    Estimation of density and hazard rate is very important to the reliability analysis of a system. In order to estimate the density and hazard rate of a hazard rate monotonously decreasing system, a new nonparametric estimator is put forward. The estimator is based on the kernel function method and optimum algorithm. Numerical experiment shows that the method is accurate enough and can be used in many cases.

  12. Non-parametric versus parametric methods in environmental sciences

    Directory of Open Access Journals (Sweden)

    Muhammad Riaz

    2016-01-01

    Full Text Available This current report intends to highlight the importance of considering background assumptions required for the analysis of real datasets in different disciplines. We will provide comparative discussion of parametric methods (that depends on distributional assumptions (like normality relative to non-parametric methods (that are free from many distributional assumptions. We have chosen a real dataset from environmental sciences (one of the application areas. The findings may be extended to the other disciplines following the same spirit.

  13. Metallomic profiling and linkage map analysis of early Parkinson's disease: a new insight to aluminum marker for the possible diagnosis.

    Directory of Open Access Journals (Sweden)

    Shiek S S J Ahmed

    Full Text Available BACKGROUND: Parkinson's disease (PD is the most common neurodegenerative disorder. The diagnosis of PD is challenging and currently none of the biochemical tests have proven to help in diagnosis. Serum metallomic analysis may suggest the possibility of diagnosis of PD. METHODOLOGY/RESULTS: The metallomic analysis was targeted on 31 elements obtained from 42 healthy controls and 45 drug naive PD patients using ICP-AES and ICP-MS to determine the concentration variations of elements between PD and normal. The targeted metallomic analysis showed the significant variations in 19 elements of patients compared to healthy control (p<0.04. The partial least squares discriminant analysis (PLS-DA showed aluminium, copper, iron, manganese and zinc are the key elements, contributes the separation of PD patients from control samples. The correlation coefficient analysis and element-element ratio confirm the imbalance of inter-elements relationship in PD patients' serum. Furthermore, elements linkage map analysis showed aluminium is a key element involved in triggering of phosphorus, which subsequently lead to imbalance of homeostatic in PD serum. The execution of neural network using elements concentrations provides 95% accuracy in detection of disease. CONCLUSIONS/SIGNIFICANCE: These results suggest that there is a disturbance in the elements homeostasis and inter-elements relationship in PD patients' serum. The analysis of serum elements helps in linking the underlying cellular processes such as oxidative stress, neuronal dysfunction and apoptosis, which are the dominating factors in PD. Also, these results increase the prospect of detection of early PD from serum through neural network algorithm.

  14. Stability analysis of glutamic acid linked peptides coupled to NOTA through different chemical linkages.

    Science.gov (United States)

    Lang, Lixin; Ma, Ying; Kiesewetter, Dale O; Chen, Xiaoyuan

    2014-11-03

    Glutamic acid is a commonly used linker to form dimeric peptides with enhanced binding affinity than their corresponding monomeric counterparts. We have previously labeled NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 (NOTA-PRGD2) [1] with [(18)F]AlF and (68)Ga for imaging tumor angiogenesis. The p-SCN-Bn-NOTA was attached to E[c(RGDyK)]2 [2] through a mini-PEG with a thiourea linkage, and the product [1] was stable at radiolabeling condition of 100 °C and pH 4.0 acetate buffer. However, when the same p-SCN-Bn-NOTA was directly attached to the α-amine of E[c(RGDfK)]2 [3], the product NOTA-Bn-NCS-E[c(RGDfK)]2 [4] became unstable under similar conditions and the release of monomeric c(RGDfK) [5] was observed. The purpose of this work was to use HPLC and LC-MS to monitor the decomposition of glutamic acid linked dimeric peptides and their NOTA derivatives. A c(RGDyK) [6] and bombesin (BBN) [7] heterodimer c(RGDyK)-E-BBN [8], and a dimeric bombesin E(BBN)2 [9], both with a glutamic acid as the linker, along with a model compound PhSCN-E[c(RGDfK)] [10] were also studied. All the compounds were dissolved in 0.5 M pH 4.0 acetate buffer at the concentration of 1 mg/mL, and 0.1 mL of each sample was heated at 100 °C for 10 min and the more stable compounds were heated for another 30 min. The samples at both time points were analyzed with analytical HPLC to monitor the decomposition of the heated samples. The samples with decomposition were further analyzed by LC-MS to determine the mass of products from the decomposition for possible structure elucidation. After 10 min heating, the obvious release of c(RGDfK) [5] was observed for NOTA-Bn-NCS-E[c(RGDfK)]2 [4] and Ph-SCN-E[c(RGDfK)] [10]. Little or no release of monomers was observed for the remaining samples at this time point. After further heating, the release of monomers was clearly observed for E[c(RGDyK)]2 [2], E[c(RGDfK)]2 [3], c(RGDyK)-E-BBN [8], and E(BBN)2 [9]. No decomposition or little decomposition was observed for NOTA

  15. Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis

    Science.gov (United States)

    Uzzal Hossain, Mohammad; Zaffar Shibly, Abu; Md. Omar, Taimur; Tous Zohora, Fatama; Sara Santona, Umme; Hossain, Md. Jakir; Hosen Khoka, Md. Sadek; Ara Keya, Chaman; Salimullah, Md.

    2016-01-01

    A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events PMID:27212841

  16. Why preferring parametric forecasting to nonparametric methods?

    Science.gov (United States)

    Jabot, Franck

    2015-05-07

    A recent series of papers by Charles T. Perretti and collaborators have shown that nonparametric forecasting methods can outperform parametric methods in noisy nonlinear systems. Such a situation can arise because of two main reasons: the instability of parametric inference procedures in chaotic systems which can lead to biased parameter estimates, and the discrepancy between the real system dynamics and the modeled one, a problem that Perretti and collaborators call "the true model myth". Should ecologists go on using the demanding parametric machinery when trying to forecast the dynamics of complex ecosystems? Or should they rely on the elegant nonparametric approach that appears so promising? It will be here argued that ecological forecasting based on parametric models presents two key comparative advantages over nonparametric approaches. First, the likelihood of parametric forecasting failure can be diagnosed thanks to simple Bayesian model checking procedures. Second, when parametric forecasting is diagnosed to be reliable, forecasting uncertainty can be estimated on virtual data generated with the fitted to data parametric model. In contrast, nonparametric techniques provide forecasts with unknown reliability. This argumentation is illustrated with the simple theta-logistic model that was previously used by Perretti and collaborators to make their point. It should convince ecologists to stick to standard parametric approaches, until methods have been developed to assess the reliability of nonparametric forecasting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Directed Graphs, Decompositions, and Spatial Linkages

    CERN Document Server

    Shai, Offer; Whiteley, Walter

    2010-01-01

    The decomposition of a system of constraints into small basic components is an important tool of design and analysis. Specifically, the decomposition of a linkage into minimal components is a central tool of analysis and synthesis of linkages. In this paper we prove that every pinned 3-isostatic (minimally rigid) graph (grounded linkage) has a unique decomposition into minimal strongly connected components (in the sense of directed graphs) which we call 3-Assur graphs. This analysis extends the Assur decompositions of plane linkages previously studied in the mathematical and the mechanical engineering literature. These 3-Assur graphs are the central building blocks for all kinematic linkages in 3-space. They share a number of key combinatorial and geometric properties with the 2-Assur graphs, including an associated lower block-triangular decomposition of the pinned rigidity matrix which provides a format for extending the motion induced by inserting one driver in a bottom Assur linkage to the joints of the e...

  18. CONSIDERATIONS OVER THE METHODOLOGY OF FINANCIAL ANALYSIS AND ITS LINKAGE WITH BANKABILITY OF EUROPEAN FUNDED INVESTMENT PROJECTS

    OpenAIRE

    Ioan TRENCA; Petria, Nicolae; Laurentiu DROJ

    2012-01-01

    European funding is considered to be one of the hot topics in Romania and all over Eastern Europe since its novelty and its expected capacity to improve the life of the newly integrated European citizens. The linkages between the European Financial Support Programmes, the private financing performed by the banking sector and the private companies which are intending to use the structural funds to finance their investments is obvious. The present paper analyzed these linkages, creates a case s...

  19. Yield Stability of Maize Hybrids Evaluated in Maize Regional Trials in Southwestern China Using Nonparametric Methods

    Institute of Scientific and Technical Information of China (English)

    LIU Yong-jian; DUAN Chuan; TIAN Meng-liang; HU Er-liang; HUANG Yu-bi

    2010-01-01

    Analysis of multi-environment trials (METs) of crops for the evaluation and recommendation of varieties is an important issue in plant breeding research. Evaluating on the both stability of performance and high yield is essential in MET analyses. The objective of the present investigation was to compare 11 nonparametric stability statistics and apply nonparametric tests for genotype-by-environment interaction (GEI) to 14 maize (Zea mays L.) genotypes grown at 25 locations in southwestern China during 2005. Results of nonparametric tests of GEI and a combined ANOVA across locations showed that both crossover and noncrossover GEI, and genotypes varied highly significantly for yield. The results of principal component analysis, correlation analysis of nonparametric statistics, and yield indicated the nonparametric statistics grouped as four distinct classes that corresponded to different agronomic and biological concepts of stability.Furthermore, high values of TOP and low values of rank-sum were associated with high mean yield, but the other nonparametric statistics were not positively correlated with mean yield. Therefore, only rank-sum and TOP methods would be useful for simultaneously selection for high yield and stability. These two statistics recommended JY686 and HX 168 as desirable and ND 108, CM 12, CN36, and NK6661 as undesirable genotypes.

  20. An analysis of the organizational linkages in the cotton industry in Benin

    NARCIS (Netherlands)

    Sinzogan, A.A.C.; Jiggins, J.; Vodouhè, S.; Kossou, D.; Totin, G.G.E.; Huis, van A.

    2007-01-01

    A study of the institutional context of the cotton industry in Benin was conducted in 2004, based on an analysis of stakeholders' interests and influence. The impacts on innovation processes and production systems are analysed with respect to farmers' organizations, the research and extension system

  1. Linkages between biodiversity loss and human health: a global indicator analysis

    NARCIS (Netherlands)

    Huynen, M.M.T.E.; Martens, P.; Groot, de R.S.

    2004-01-01

    The association between health and biodiversity loss was explored by means of regression analysis on a global scale, with control for confounding by socio-economic developments. For this we selected indicators of human health (life expectancy, disability adjusted life expectancy, infant mortality

  2. Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis

    Science.gov (United States)

    Lai, Hsin-Yi; Chen, You-Yin; Lin, Sheng-Huang; Lo, Yu-Chun; Tsang, Siny; Chen, Shin-Yuan; Zhao, Wan-Ting; Chao, Wen-Hung; Chang, Yao-Chuan; Wu, Robby; Shih, Yen-Yu I.; Tsai, Sheng-Tsung; Jaw, Fu-Shan

    2011-06-01

    Automatic spike sorting is a prerequisite for neuroscience research on multichannel extracellular recordings of neuronal activity. A novel spike sorting framework, combining efficient feature extraction and an unsupervised clustering method, is described here. Wavelet transform (WT) is adopted to extract features from each detected spike, and the Kolmogorov-Smirnov test (KS test) is utilized to select discriminative wavelet coefficients from the extracted features. Next, an unsupervised single linkage clustering method based on grey relational analysis (GSLC) is applied for spike clustering. The GSLC uses the grey relational grade as the similarity measure, instead of the Euclidean distance for distance calculation; the number of clusters is automatically determined by the elbow criterion in the threshold-cumulative distribution. Four simulated data sets with four noise levels and electrophysiological data recorded from the subthalamic nucleus of eight patients with Parkinson's disease during deep brain stimulation surgery are used to evaluate the performance of GSLC. Feature extraction results from the use of WT with the KS test indicate a reduced number of feature coefficients, as well as good noise rejection, despite similar spike waveforms. Accordingly, the use of GSLC for spike sorting achieves high classification accuracy in all simulated data sets. Moreover, J-measure results in the electrophysiological data indicating that the quality of spike sorting is adequate with the use of GSLC.

  3. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

    Energy Technology Data Exchange (ETDEWEB)

    Labuda, M.; Glorieux, F.H. [McGill Univ., Montreal (Canada); Labuda, D.; Korab-Laskowska, M. [Universite de Montreal (Canada)] [and others

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.

  4. Eco-Health linkages: assessing the role of ecosystem goods and services on human health using causal criteria analysis.

    Science.gov (United States)

    de Jesus Crespo, Rebeca; Fulford, Richard

    2017-08-01

    In the last decade, we saw an upsurge of studies evaluating the role of ecosystem goods and services (EGS) on human health (Eco-Health). Most of this work consists of observational research of intermediate processes and few address the full pathways from ecosystem to EGS to human health, limiting our ability to assess causality. We conducted a causal criteria analysis of Eco-Health literature using Eco-Evidence, a software tool that helps evaluate evidence of cause-effect relationships. We focus on the context of green spaces providing "buffering" EGS that may influence disease. We found support for a causal linkage between green spaces and all of the EGS tested, and sufficient evidence linking EGS to gastro intestinal disease and heat morbidities. Inconsistencies were found when assessing the link between EGS to cardiovascular and respiratory diseases. Few studies directly link green spaces to health. Those that do, support a connection to cardiovascular disease, and heat morbidities, but provide inconsistent evidence regarding respiratory illness. Our results help establish an agenda to shape future Eco-Health research and define priorities for managing green spaces to provide human health benefits.

  5. Generative Temporal Modelling of Neuroimaging - Decomposition and Nonparametric Testing

    DEFF Research Database (Denmark)

    Hald, Ditte Høvenhoff

    The goal of this thesis is to explore two improvements for functional magnetic resonance imaging (fMRI) analysis; namely our proposed decomposition method and an extension to the non-parametric testing framework. Analysis of fMRI allows researchers to investigate the functional processes...... of the brain, and provides insight into neuronal coupling during mental processes or tasks. The decomposition method is a Gaussian process-based independent components analysis (GPICA), which incorporates a temporal dependency in the sources. A hierarchical model specification is used, featuring both...

  6. Investigating fault propagation and segment linkage using throw distribution analysis within the Agbada formation of Ewan and Oloye fields, northwestern Niger delta

    Science.gov (United States)

    Durogbitan, Abimbola Adewole

    2016-08-01

    Throw distribution analysis of the key stratigraphic surfaces (sequence boundaries and maximum flooding surfaces) across faults has allowed detailed investigation of the tectonic history within the Ewan and Oloye fields, northwestern Niger delta. The structure in the studied area is dominated by growth fault systems which are listric in cross section and concave to the basin in plan-view. Generally, the faults are active down to 2000 m depth before they die out or sole into the underlying shale. The hanging-wall blocks of growth faults are deformed into broad rollover anticlines, with some synthetic and antithetic faults initiated from the anticline crests, and fault splays off major faults, further complicating these structures. Stratigraphic key surfaces within the syn-faulting succession range in age from 16.7 to 10.35 Ma. Periods of maximum and minimum throw are established from 2-Dimensional throw distribution on the growth fault plane. Throw distribution allows analysis of growth fault nucleation, propagation and linkage. Each fault nucleated at different and a distinct interval within the stratigraphic section, as a result of the paleo-stress distribution between the interacting faults. Nucleation and linkage positions can be identified at points of maximum and minimum throw respectively. Following nucleation, faults propagated radially and linked to form the present geometry. Within the study area, fault propagation and segment linkage (lateral and vertical) are important features of the fault system. Understanding of growth fault evolution and linkage has greatly improved prediction of seal potential, trap geometry and migration. The accurate timing of the segment linkage has helped to evaluate the seal risk.

  7. Recent Advances and Trends in Nonparametric Statistics

    CERN Document Server

    Akritas, MG

    2003-01-01

    The advent of high-speed, affordable computers in the last two decades has given a new boost to the nonparametric way of thinking. Classical nonparametric procedures, such as function smoothing, suddenly lost their abstract flavour as they became practically implementable. In addition, many previously unthinkable possibilities became mainstream; prime examples include the bootstrap and resampling methods, wavelets and nonlinear smoothers, graphical methods, data mining, bioinformatics, as well as the more recent algorithmic approaches such as bagging and boosting. This volume is a collection o

  8. Correlated Non-Parametric Latent Feature Models

    CERN Document Server

    Doshi-Velez, Finale

    2012-01-01

    We are often interested in explaining data through a set of hidden factors or features. When the number of hidden features is unknown, the Indian Buffet Process (IBP) is a nonparametric latent feature model that does not bound the number of active features in dataset. However, the IBP assumes that all latent features are uncorrelated, making it inadequate for many realworld problems. We introduce a framework for correlated nonparametric feature models, generalising the IBP. We use this framework to generate several specific models and demonstrate applications on realworld datasets.

  9. Nonparametric correlation models for portfolio allocation

    DEFF Research Database (Denmark)

    Aslanidis, Nektarios; Casas, Isabel

    2013-01-01

    This article proposes time-varying nonparametric and semiparametric estimators of the conditional cross-correlation matrix in the context of portfolio allocation. Simulations results show that the nonparametric and semiparametric models are best in DGPs with substantial variability or structural...... breaks in correlations. Only when correlations are constant does the parametric DCC model deliver the best outcome. The methodologies are illustrated by evaluating two interesting portfolios. The first portfolio consists of the equity sector SPDRs and the S&P 500, while the second one contains major...

  10. Enhanced understanding of ectoparasite–host trophic linkages on coral reefs through stable isotope analysis

    Directory of Open Access Journals (Sweden)

    Amanda W.J. Demopoulos

    2015-04-01

    Full Text Available Parasitism, although the most common type of ecological interaction, is usually ignored in food web models and studies of trophic connectivity. Stable isotope analysis is widely used in assessing the flow of energy in ecological communities and thus is a potentially valuable tool in understanding the cryptic trophic relationships mediated by parasites. In an effort to assess the utility of stable isotope analysis in understanding the role of parasites in complex coral-reef trophic systems, we performed stable isotope analysis on three common Caribbean reef fish hosts and two kinds of ectoparasitic isopods: temporarily parasitic gnathiids (Gnathia marleyi and permanently parasitic cymothoids (Anilocra. To further track the transfer of fish-derived carbon (energy from parasites to parasite consumers, gnathiids from host fish were also fed to captive Pederson shrimp (Ancylomenes pedersoni for at least 1 month. Parasitic isopods had δ13C and δ15N values similar to their host, comparable with results from the small number of other host–parasite studies that have employed stable isotopes. Adult gnathiids were enriched in 15N and depleted in 13C relative to juvenile gnathiids, providing insights into the potential isotopic fractionation associated with blood-meal assimilation and subsequent metamorphosis. Gnathiid-fed Pedersen shrimp also had δ13C values consistent with their food source and enriched in 15N as predicted due to trophic fractionation. These results further indicate that stable isotopes can be an effective tool in deciphering cryptic feeding relationships involving parasites and their consumers, and the role of parasites and cleaners in carbon transfer in coral-reef ecosystems specifically.

  11. Enhanced understanding of ectoparasite: host trophic linkages on coral reefs through stable isotope analysis

    Science.gov (United States)

    Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2015-01-01

    Parasitism, although the most common type of ecological interaction, is usually ignored in food web models and studies of trophic connectivity. Stable isotope analysis is widely used in assessing the flow of energy in ecological communities and thus is a potentially valuable tool in understanding the cryptic trophic relationships mediated by parasites. In an effort to assess the utility of stable isotope analysis in understanding the role of parasites in complex coral-reef trophic systems, we performed stable isotope analysis on three common Caribbean reef fish hosts and two kinds of ectoparasitic isopods: temporarily parasitic gnathiids (Gnathia marleyi) and permanently parasitic cymothoids (Anilocra). To further track the transfer of fish-derived carbon (energy) from parasites to parasite consumers, gnathiids from host fish were also fed to captive Pederson shrimp (Ancylomenes pedersoni) for at least 1 month. Parasitic isopods had δ13C and δ15N values similar to their host, comparable with results from the small number of other host–parasite studies that have employed stable isotopes. Adult gnathiids were enriched in 15N and depleted in13C relative to juvenile gnathiids, providing insights into the potential isotopic fractionation associated with blood-meal assimilation and subsequent metamorphosis. Gnathiid-fed Pedersen shrimp also had δ13C values consistent with their food source and enriched in 15N as predicted due to trophic fractionation. These results further indicate that stable isotopes can be an effective tool in deciphering cryptic feeding relationships involving parasites and their consumers, and the role of parasites and cleaners in carbon transfer in coral-reef ecosystems specifically.

  12. 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.

  13. Dubin's Minimal Linkage Construct Revisited.

    Science.gov (United States)

    Rogers, Donald P.

    This paper contains a theoretical analysis and empirical study that support the major premise of Robert Dubin's minimal-linkage construct-that restricting communication links increases organizational stability. The theoretical analysis shows that fewer communication links are associated with less uncertainty, more redundancy, and greater…

  14. Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia.

    Science.gov (United States)

    Shmulewitz, Dvora; Heath, Simon C; Blundell, Maude L; Han, Zhihua; Sharma, Ratnendra; Salit, Jacqueline; Auerbach, Steven B; Signorini, Stefano; Breslow, Jan L; Stoffel, Markus; Friedman, Jeffrey M

    2006-03-07

    Obesity, diabetes, hypertension, and heart disease are highly heritable conditions that in aggregate are the major causes of morbidity and mortality in the developed world and are growing problems in developing countries. To map the causal genes, we conducted a population screen for these conditions on the Pacific Island of Kosrae. Family history and genetic data were used to construct a pedigree for the island. Analysis of the pedigree showed highly significant heritability for the metabolic traits under study. DNA samples from 2,188 participants were genotyped with 405 microsatellite markers with an average intermarker distance of 11 cM. A protocol using loki, a Markov chain Monte Carlo sampling method, was developed to analyze the Kosraen pedigree for height, a model quantitative trait. Robust quantitative trait loci for height were found on 10q21 and 1p31. This protocol was used to map a set of metabolic traits, including plasma leptin to chromosome region 5q35; systolic blood pressure to 20p12; total cholesterol to 19p13, 12q24, and 16qter; hip circumference to 10q25 and 4q23; body mass index to 18p11 and 20q13; apolipoprotein B to 2p24-25; weight to 18q21; and fasting blood sugar to 1q31-1q43. Several of these same chromosomal regions have been identified in previous studies validating the use of loki. These studies add information about the genetics of the metabolic syndrome and establish an analytical approach for linkage analysis of complex pedigrees. These results also lay the foundation for whole genome scans with dense sets of SNPs aimed to identifying causal genes.

  15. Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.

    Science.gov (United States)

    Alley, William R; Novotny, Milos V

    2010-06-04

    A number of alterations to the normal glycomic profile have been previously described for a number of diseases and disorders, thus underscoring the medical importance of studying the glycans associated with proteins present in biological samples. An important alteration in cancer progression is an increased level of alpha2,6-sialylation, which aids in increasing the metastatic potential of tumor cells. Here we report a glycomic method that selectively amidates alpha2,6-linked sialic acids, while those that are alpha2,3-linked undergo spontaneous lactonization. Following subsequent permethylation, MALDI-TOF MS analysis revealed that many sialylated glycans present on glycoproteins found in blood serum featured increased levels of alpha2,6-sialylation in breast cancer samples. On the basis of the altered ratios of alpha2,3-linked to alpha2,6-linked sialic acids, many of these glycans became diagnostically relevant when they did not act as such indicators when based on traditional glycomic profiling alone.

  16. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q.

    Science.gov (United States)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-06-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.

  17. Construction of a genetic linkage map and genetic analysis of domestication related traits in mungbean (Vigna radiata.

    Directory of Open Access Journals (Sweden)

    Takehisa Isemura

    Full Text Available The genetic differences between mungbean and its presumed wild ancestor were analyzed for domestication related traits by QTL mapping. A genetic linkage map of mungbean was constructed using 430 SSR and EST-SSR markers from mungbean and its related species, and all these markers were mapped onto 11 linkage groups spanning a total of 727.6 cM. The present mungbean map is the first map where the number of linkage groups coincided with the haploid chromosome number of mungbean. In total 105 QTLs and genes for 38 domestication related traits were identified. Compared with the situation in other Vigna crops, many linkage groups have played an important role in the domestication of mungbean. In particular the QTLs with high contribution were distributed on seven out of 11 linkage groups. In addition, a large number of QTLs with small contribution were found. The accumulation of many mutations with large and/or small contribution has contributed to the differentiation between wild and cultivated mungbean. The useful QTLs for seed size, pod dehiscence and pod maturity that have not been found in other Asian Vigna species were identified in mungbean, and these QTLs may play the important role as new gene resources for other Asian Vigna species. The results provide the foundation that will be useful for improvement of mungbean and related legumes.

  18. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA.

  19. Thirty years of nonparametric item response theory

    NARCIS (Netherlands)

    Molenaar, W.

    2001-01-01

    Relationships between a mathematical measurement model and its real-world applications are discussed. A distinction is made between large data matrices commonly found in educational measurement and smaller matrices found in attitude and personality measurement. Nonparametric methods are evaluated fo

  20. 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…

  1. Nonparametric confidence intervals for monotone functions

    NARCIS (Netherlands)

    Groeneboom, P.; Jongbloed, G.

    2015-01-01

    We study nonparametric isotonic confidence intervals for monotone functions. In [Ann. Statist. 29 (2001) 1699–1731], pointwise confidence intervals, based on likelihood ratio tests using the restricted and unrestricted MLE in the current status model, are introduced. We extend the method to the trea

  2. Nonparametric confidence intervals for monotone functions

    NARCIS (Netherlands)

    Groeneboom, P.; Jongbloed, G.

    2015-01-01

    We study nonparametric isotonic confidence intervals for monotone functions. In [Ann. Statist. 29 (2001) 1699–1731], pointwise confidence intervals, based on likelihood ratio tests using the restricted and unrestricted MLE in the current status model, are introduced. We extend the method to the

  3. Panel data specifications in nonparametric kernel regression

    DEFF Research Database (Denmark)

    Czekaj, Tomasz Gerard; Henningsen, Arne

    parametric panel data estimators to analyse the production technology of Polish crop farms. The results of our nonparametric kernel regressions generally differ from the estimates of the parametric models but they only slightly depend on the choice of the kernel functions. Based on economic reasoning, we...

  4. Identification of Single Nucleotide Polymorphisms and analysis of Linkage Disequilibrium in sunflower elite inbred lines using the candidate gene approach

    Directory of Open Access Journals (Sweden)

    Heinz Ruth A

    2008-01-01

    Full Text Available Abstract Background Association analysis is a powerful tool to identify gene loci that may contribute to phenotypic variation. This includes the estimation of nucleotide diversity, the assessment of linkage disequilibrium structure (LD and the evaluation of selection processes. Trait mapping by allele association requires a high-density map, which could be obtained by the addition of Single Nucleotide Polymorphisms (SNPs and short insertion and/or deletions (indels to SSR and AFLP genetic maps. Nucleotide diversity analysis of randomly selected candidate regions is a promising approach for the success of association analysis and fine mapping in the sunflower genome. Moreover, knowledge of the distance over which LD persists, in agronomically meaningful sunflower accessions, is important to establish the density of markers and the experimental design for association analysis. Results A set of 28 candidate genes related to biotic and abiotic stresses were studied in 19 sunflower inbred lines. A total of 14,348 bp of sequence alignment was analyzed per individual. In average, 1 SNP was found per 69 nucleotides and 38 indels were identified in the complete data set. The mean nucleotide polymorphism was moderate (θ = 0.0056, as expected for inbred materials. The number of haplotypes per region ranged from 1 to 9 (mean = 3.54 ± 1.88. Model-based population structure analysis allowed detection of admixed individuals within the set of accessions examined. Two putative gene pools were identified (G1 and G2, with a large proportion of the inbred lines being assigned to one of them (G1. Consistent with the absence of population sub-structuring, LD for G1 decayed more rapidly (r2 = 0.48 at 643 bp; trend line, pooled data than the LD trend line for the entire set of 19 individuals (r2 = 0.64 for the same distance. Conclusion Knowledge about the patterns of diversity and the genetic relationships between breeding materials could be an invaluable aid in crop

  5. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    OpenAIRE

    2007-01-01

    Abstract Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and ...

  6. Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.

    Science.gov (United States)

    Ichihara, Sahoko; Yamamoto, Ken; Asano, Hiroyuki; Nakatochi, Masahiro; Sukegawa, Mayo; Ichihara, Gaku; Izawa, Hideo; Hirashiki, Akihiro; Takatsu, Fumimaro; Umeda, Hisashi; Iwase, Mitsunori; Inagaki, Haruo; Hirayama, Haruo; Sone, Takahito; Nishigaki, Kazuhiko; Minatoguchi, Shinya; Cho, Myeong-Chan; Jang, Yangsoo; Kim, Hyo-Soo; Park, Jeong E; Tada-Oikawa, Saeko; Kitajima, Hidetoshi; Matsubara, Tatsuaki; Sunagawa, Kenji; Shimokawa, Hiroaki; Kimura, Akinori; Lee, Jong-Young; Murohara, Toyoaki; Inoue, Ituro; Yokota, Mitsuhiro

    2013-12-01

    Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

  7. BATTEN-DISEASE GENE, CLN3 - LINKAGE DISEQUILIBRIUM MAPPING IN THE FINNISH POPULATION, AND ANALYSIS OF EUROPEAN HAPLOTYPES

    NARCIS (Netherlands)

    MITCHISON, HM; ORAWE, AM; TASCHNER, PEM; SANDKUIJL, LA; SANTAVUORI, P; DEVOS, N; BREUNING, MH; MOLE, SE; GARDINER, RM; JARVELA, IE

    The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjogren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers-D16S288, D16S299, D16S298, and SPN-are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These

  8. Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge.

    Science.gov (United States)

    Jain, Kriti M; Zulliger, Rose; Maulsby, Cathy; Kim, Jeeyon Janet; Charles, Vignetta; Riordan, Maura; Holtgrave, David

    2016-05-01

    Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds.

  9. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2

    Energy Technology Data Exchange (ETDEWEB)

    San Millan, J.L.; Viribay, M.; Peral, B.; Moreno, F. [Unidad de Genetica Molecular, Madrid (Spain); Martinez, I. [Hospital de Galdacano (Spain); Weissenbach, J. [Genethon, Evry (France)

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In {approximately}86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of {approximately}1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. 25 refs., 4 figs., 1 tab.

  10. Are Public-Private Partnerships a Source of Greater Efficiency in Water Supply? Results of a Non-Parametric Performance Analysis Relating to the Italian Industry

    Directory of Open Access Journals (Sweden)

    Corrado lo Storto

    2013-12-01

    Full Text Available This article reports the outcome of a performance study of the water service provision industry in Italy. The study evaluates the efficiency of 21 “private or public-private” equity and 32 “public” equity water service operators and investigates controlling factors. In particular, the influence that the operator typology and service management nature - private vs. public - has on efficiency is assessed. The study employed a two-stage Data Envelopment Analysis methodology. In the first stage, the operational efficiency of water supply operators is calculated by implementing a conventional BCC DEA model, that uses both physical infrastructure and financial input and output variables to explore economies of scale. In the second stage, bootstrapped DEA and Tobit regression are performed to estimate the influence that a number of environmental factors have on water supplier efficiency. The results show that the integrated water provision industry in Italy is characterized by operational inefficiencies of service operators, and scale and agglomeration economies may have a not negligible effect on efficiency. In addition, the operator typology and its geographical location affect efficiency.

  11. 交通拥堵持续时间的非参数生存分析%Nonparametric survival analysis of traffic congestion duration time

    Institute of Scientific and Technical Information of China (English)

    杨小宝; 周映雪

    2013-01-01

    The hazard-based traffic congestion duration model was established through survival analysis method. Based on the empirical traffic flow data on the Third Ring Road in Beijing, the traffic congestion duration of the Third Ring Road was estimated. The results show that 56% of the congestion durations of road segments on the Third Ring Road are not larger than four minutes. 90% of the congestion durations are not larger than 12 minutes. The hazard rate is less than 10% when the duration is larger than 12 minutes. The occurrence frequency of congestion on the outer ring is larger than the inner ring while the congestion duration on the inner ring is longer than the duration on the outer ring.%采用生存分析的非参数方法,建立基于风险的交通拥堵持续时间模型,根据北京市三环快速路的交通流数据,对三环道路交通拥堵持续时间进行了估计.结果表明:三环各路段的拥堵持续时间56%在4 min以内,90%在12 min之内;当拥堵持续时间超过12 min之后拥堵结束的可能性小于10%.外环比内环更容易发生拥堵,但当拥堵发生后内环的拥堵持续时间更长.

  12. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs.

    Directory of Open Access Journals (Sweden)

    Delphine Fradin

    Full Text Available BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. METHODS AND FINDINGS: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE and the National Institute of Mental Health (NIMH autism repository. We report parametric (GH, Genehunter and allele-sharing linkage (Aspex results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH = 3.79, empirical p<0.005 and LOD(Aspex = 2.96, p = 0.008, 15 (LOD(GH = 3.09, empirical p<0.005 and LOD(Aspex = 3.62, empirical p = 0.003 and 20 (LOD(GH = 3.36, empirical p<0.005 and LOD(Aspex = 3.38, empirical p = 0.006. CONCLUSIONS: These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.

  13. 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.

  14. A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11.

    Science.gov (United States)

    Oedegaard, K J; Greenwood, T A; Lunde, A; Fasmer, O B; Akiskal, H S; Kelsoe, J R

    2010-04-01

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a

  15. a Multivariate Downscaling Model for Nonparametric Simulation of Daily Flows

    Science.gov (United States)

    Molina, J. M.; Ramirez, J. A.; Raff, D. A.

    2011-12-01

    A multivariate, stochastic nonparametric framework for stepwise disaggregation of seasonal runoff volumes to daily streamflow is presented. The downscaling process is conditional on volumes of spring runoff and large-scale ocean-atmosphere teleconnections and includes a two-level cascade scheme: seasonal-to-monthly disaggregation first followed by monthly-to-daily disaggregation. The non-parametric and assumption-free character of the framework allows consideration of the random nature and nonlinearities of daily flows, which parametric models are unable to account for adequately. This paper examines statistical links between decadal/interannual climatic variations in the Pacific Ocean and hydrologic variability in US northwest region, and includes a periodicity analysis of climate patterns to detect coherences of their cyclic behavior in the frequency domain. We explore the use of such relationships and selected signals (e.g., north Pacific gyre oscillation, southern oscillation, and Pacific decadal oscillation indices, NPGO, SOI and PDO, respectively) in the proposed data-driven framework by means of a combinatorial approach with the aim of simulating improved streamflow sequences when compared with disaggregated series generated from flows alone. A nearest neighbor time series bootstrapping approach is integrated with principal component analysis to resample from the empirical multivariate distribution. A volume-dependent scaling transformation is implemented to guarantee the summability condition. In addition, we present a new and simple algorithm, based on nonparametric resampling, that overcomes the common limitation of lack of preservation of historical correlation between daily flows across months. The downscaling framework presented here is parsimonious in parameters and model assumptions, does not generate negative values, and produces synthetic series that are statistically indistinguishable from the observations. We present evidence showing that both

  16. Nonparametric tests for pathwise properties of semimartingales

    CERN Document Server

    Cont, Rama; 10.3150/10-BEJ293

    2011-01-01

    We propose two nonparametric tests for investigating the pathwise properties of a signal modeled as the sum of a L\\'{e}vy process and a Brownian semimartingale. Using a nonparametric threshold estimator for the continuous component of the quadratic variation, we design a test for the presence of a continuous martingale component in the process and a test for establishing whether the jumps have finite or infinite variation, based on observations on a discrete-time grid. We evaluate the performance of our tests using simulations of various stochastic models and use the tests to investigate the fine structure of the DM/USD exchange rate fluctuations and SPX futures prices. In both cases, our tests reveal the presence of a non-zero Brownian component and a finite variation jump component.

  17. Nonparametric Transient Classification using Adaptive Wavelets

    CERN Document Server

    Varughese, Melvin M; Stephanou, Michael; Bassett, Bruce A

    2015-01-01

    Classifying transients based on multi band light curves is a challenging but crucial problem in the era of GAIA and LSST since the sheer volume of transients will make spectroscopic classification unfeasible. Here we present a nonparametric classifier that uses the transient's light curve measurements to predict its class given training data. It implements two novel components: the first is the use of the BAGIDIS wavelet methodology - a characterization of functional data using hierarchical wavelet coefficients. The second novelty is the introduction of a ranked probability classifier on the wavelet coefficients that handles both the heteroscedasticity of the data in addition to the potential non-representativity of the training set. The ranked classifier is simple and quick to implement while a major advantage of the BAGIDIS wavelets is that they are translation invariant, hence they do not need the light curves to be aligned to extract features. Further, BAGIDIS is nonparametric so it can be used for blind ...

  18. Bayesian nonparametric estimation for Quantum Homodyne Tomography

    OpenAIRE

    Naulet, Zacharie; Barat, Eric

    2016-01-01

    We estimate the quantum state of a light beam from results of quantum homodyne tomography noisy measurements performed on identically prepared quantum systems. We propose two Bayesian nonparametric approaches. The first approach is based on mixture models and is illustrated through simulation examples. The second approach is based on random basis expansions. We study the theoretical performance of the second approach by quantifying the rate of contraction of the posterior distribution around ...

  19. Using Linkage Analysis to Detect Gene-Gene Interactions. 2. Improved Reliability and Extension to More-Complex Models.

    Directory of Open Access Journals (Sweden)

    Susan E Hodge

    Full Text Available Detecting gene-gene interaction in complex diseases has become an important priority for common disease genetics, but most current approaches to detecting interaction start with disease-marker associations. These approaches are based on population allele frequency correlations, not genetic inheritance, and therefore cannot exploit the rich information about inheritance contained within families. They are also hampered by issues of rigorous phenotype definition, multiple test correction, and allelic and locus heterogeneity. We recently developed, tested, and published a powerful gene-gene interaction detection strategy based on conditioning family data on a known disease-causing allele or a disease-associated marker allele4. We successfully applied the method to disease data and used computer simulation to exhaustively test the method for some epistatic models. We knew that the statistic we developed to indicate interaction was less reliable when applied to more-complex interaction models. Here, we improve the statistic and expand the testing procedure. We computer-simulated multipoint linkage data for a disease caused by two interacting loci. We examined epistatic as well as additive models and compared them with heterogeneity models. In all our models, the at-risk genotypes are "major" in the sense that among affected individuals, a substantial proportion has a disease-related genotype. One of the loci (A has a known disease-related allele (as would have been determined from a previous analysis. We removed (pruned family members who did not carry this allele; the resultant dataset is referred to as "stratified." This elimination step has the effect of raising the "penetrance" and detectability at the second locus (B. We used the lod scores for the stratified and unstratified data sets to calculate a statistic that either indicated the presence of interaction or indicated that no interaction was detectable. We show that the new method is robust

  20. portfolio optimization based on nonparametric estimation methods

    Directory of Open Access Journals (Sweden)

    mahsa ghandehari

    2017-03-01

    Full Text Available One of the major issues investors are facing with in capital markets is decision making about select an appropriate stock exchange for investing and selecting an optimal portfolio. This process is done through the risk and expected return assessment. On the other hand in portfolio selection problem if the assets expected returns are normally distributed, variance and standard deviation are used as a risk measure. But, the expected returns on assets are not necessarily normal and sometimes have dramatic differences from normal distribution. This paper with the introduction of conditional value at risk ( CVaR, as a measure of risk in a nonparametric framework, for a given expected return, offers the optimal portfolio and this method is compared with the linear programming method. The data used in this study consists of monthly returns of 15 companies selected from the top 50 companies in Tehran Stock Exchange during the winter of 1392 which is considered from April of 1388 to June of 1393. The results of this study show the superiority of nonparametric method over the linear programming method and the nonparametric method is much faster than the linear programming method.

  1. Structure-Function Analysis of a Mixed-linkage β-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4.

    Science.gov (United States)

    McGregor, Nicholas; Morar, Mariya; Fenger, Thomas Hauch; Stogios, Peter; Lenfant, Nicolas; Yin, Victor; Xu, Xiaohui; Evdokimova, Elena; Cui, Hong; Henrissat, Bernard; Savchenko, Alexei; Brumer, Harry

    2016-01-15

    The recent classification of glycoside hydrolase family 5 (GH5) members into subfamilies enhances the prediction of substrate specificity by phylogenetic analysis. However, the small number of well characterized members is a current limitation to understanding the molecular basis of the diverse specificity observed across individual GH5 subfamilies. GH5 subfamily 4 (GH5_4) is one of the largest, with known activities comprising (carboxymethyl)cellulases, mixed-linkage endo-glucanases, and endo-xyloglucanases. Through detailed structure-function analysis, we have revisited the characterization of a classic GH5_4 carboxymethylcellulase, PbGH5A (also known as Orf4, carboxymethylcellulase, and Cel5A), from the symbiotic rumen Bacteroidetes Prevotella bryantii B14. We demonstrate that carboxymethylcellulose and phosphoric acid-swollen cellulose are in fact relatively poor substrates for PbGH5A, which instead exhibits clear primary specificity for the plant storage and cell wall polysaccharide, mixed-linkage β-glucan. Significant activity toward the plant cell wall polysaccharide xyloglucan was also observed. Determination of PbGH5A crystal structures in the apo-form and in complex with (xylo)glucan oligosaccharides and an active-site affinity label, together with detailed kinetic analysis using a variety of well defined oligosaccharide substrates, revealed the structural determinants of polysaccharide substrate specificity. In particular, this analysis highlighted the PbGH5A active-site motifs that engender predominant mixed-linkage endo-glucanase activity vis à vis predominant endo-xyloglucanases in GH5_4. However the detailed phylogenetic analysis of GH5_4 members did not delineate particular clades of enzymes sharing these sequence motifs; the phylogeny was instead dominated by bacterial taxonomy. Nonetheless, our results provide key enzyme functional and structural reference data for future bioinformatics analyses of (meta)genomes to elucidate the biology of

  2. Genetic linkage map and expression analysis of genes expressed in the lamellae of the edible basidiomycete Pleurotus ostreatus.

    Science.gov (United States)

    Park, Sang-Kyu; Peñas, María M; Ramírez, Lucía; Pisabarro, Antonio G

    2006-05-01

    Pleurotus ostreatus is an industrially cultivated basidiomycete with nutritional and environmental applications. Its genome contains 35 Mbp organized in 11 chromosomes. There is currently available a genetic linkage map based predominantly on anonymous molecular markers complemented with the mapping of QTLs controlling growth rate and industrial productivity. To increase the saturation of the existing linkage maps, we have identified and mapped 82 genes expressed in the lamellae. Their manual annotation revealed that 34.1% of the lamellae-expressed and 71.5% of the lamellae-specific genes correspond to previously unknown sequences or to hypothetical proteins without a clearly established function. Furthermore, the expression pattern of some genes provides an experimental basis for studying gene regulation during the change from vegetative to reproductive growth. Finally, the identification of various differentially regulated genes involved in protein metabolism suggests the relevance of these processes in fruit body formation and maturation.

  3. Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs

    OpenAIRE

    Delphine Fradin; Keely Cheslack-Postava; Christine Ladd-Acosta; Craig Newschaffer; Aravinda Chakravarti; Arking, Dan E.; Andrew Feinberg; M Daniele Fallin

    2010-01-01

    BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to d...

  4. Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study

    OpenAIRE

    Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

    2016-01-01

    Objectives The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. Design This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004–2010, we calculated age-standardised death rates (SDR) and standardised morta...

  5. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    OpenAIRE

    Tereza Manousaki; Alexandros Tsakogiannis; Taggart, John B.; Christos Palaiokostas; Dimitris Tsaparis; Jacques Lagnel; Dimitrios Chatziplis; Antonios Magoulas; Nikos Papandroulakis; Mylonas, Constantinos C.; Tsigenopoulos, Costas S

    2016-01-01

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking the genotype to phenotype allowing fine-mapping of ...

  6. High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea

    Science.gov (United States)

    Gaur, Rashmi; Jeena, Ganga; Shah, Niraj; Gupta, Shefali; Pradhan, Seema; Tyagi, Akhilesh K; Jain, Mukesh; Chattopadhyay, Debasis; Bhatia, Sabhyata

    2015-01-01

    This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties. PMID:26303721

  7. A linkage study between the GABAA beta2 and GABAA gamma2 subunit genes and major psychoses.

    Science.gov (United States)

    Ambrósio, Alda M; Kennedy, James L; Macciardi, Fabio; King, Nicole; Azevedo, Maria H; Oliveira, Catarina R; Pato, Carlos N

    2005-01-01

    Alterations of the gamma-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses. Restriction fragment length polymorphisms associated with the human gamma-aminobutyric acid type A (GABAA) beta2 and GABAA gamma2 subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses. Thirty-two schizophrenic families and 25 bipolar families were tested for linkage. Nonparametric linkage (NPL) analysis performed by GENEHUNTER showed no significant NPL scores for both genes in schizophrenia (GABAA beta2: NPL narrow= -0.450; NPL broad= -0.808; GABAA gamma2: NPL narrow=0.177; NPL broad= -0.051) or bipolar disorder (GABAA beta2: NPL narrow=0.834; NPL broad=0.783; GABAA gamma2: NPL narrow= -0.159; NPL broad=0.070). Linkage analysis does not support the hypothesis that variants within the GABAA beta2 and GABAA gamma2 genes are significantly linked to major psychoses in a Portuguese population.

  8. Genetic linkage of bipolar disorder to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations.

    Science.gov (United States)

    Pato, Carlos N; Middleton, Frank A; Gentile, Karen L; Morley, Christopher P; Medeiros, Helena; Macedo, Antonio; Azevedo, M Helena; Pato, Michele T

    2005-04-05

    We recently reported genome-wide significant linkage to chromosome 6q for bipolar disorder, in a study of 25 Portuguese families, using the Human Mapping Assay Xba 131 (HMA10K). To explore the generalizability of this finding, we reanalyzed our SNP linkage data according to the families' geographic origin. Specifically, the 25 families included 20 families from the Portuguese island collection (PIC; 15 families from the Azores Islands and 5 from the Madeira Islands) and 5 families from continental Portugal. Non-parametric linkage analysis (NPL) was performed as previously described and indicated that each of these subpopulations showed evidence of linkage for the same region. To further address the potential generalizability of these findings to other populations, we have also examined allelic heterozygosity in our subpopulations and in three reference populations (Caucasian, East Asian, and African-American). This analysis indicated that the PIC population is highly correlated to the Caucasian reference population (R = 0.86) for all of chromosome 6. In contrast allelic heterozygosity was more weakly correlated between PIC and both East Asian (R = 0.37) and African-American (R = 0.32) reference populations. Taken together these observations suggest a shared genetic liability among Portuguese populations for bipolar disorder on chromosome 6q, and that the PIC population is likely representative of Caucasians in general. Copyright 2005 Wiley-Liss, Inc.

  9. Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium

    DEFF Research Database (Denmark)

    Shete, Sanjay; Lau, Ching C; Houlston, Richard S;

    2011-01-01

    -fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge...... nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U...

  10. Nonparametric Analyses of Log-Periodic Precursors to Financial Crashes

    Science.gov (United States)

    Zhou, Wei-Xing; Sornette, Didier

    We apply two nonparametric methods to further test the hypothesis that log-periodicity characterizes the detrended price trajectory of large financial indices prior to financial crashes or strong corrections. The term "parametric" refers here to the use of the log-periodic power law formula to fit the data; in contrast, "nonparametric" refers to the use of general tools such as Fourier transform, and in the present case the Hilbert transform and the so-called (H, q)-analysis. The analysis using the (H, q)-derivative is applied to seven time series ending with the October 1987 crash, the October 1997 correction and the April 2000 crash of the Dow Jones Industrial Average (DJIA), the Standard & Poor 500 and Nasdaq indices. The Hilbert transform is applied to two detrended price time series in terms of the ln(tc-t) variable, where tc is the time of the crash. Taking all results together, we find strong evidence for a universal fundamental log-frequency f=1.02±0.05 corresponding to the scaling ratio λ=2.67±0.12. These values are in very good agreement with those obtained in earlier works with different parametric techniques. This note is extracted from a long unpublished report with 58 figures available at , which extensively describes the evidence we have accumulated on these seven time series, in particular by presenting all relevant details so that the reader can judge for himself or herself the validity and robustness of the results.

  11. Wavelet Estimators in Nonparametric Regression: A Comparative Simulation Study

    Directory of Open Access Journals (Sweden)

    Anestis Antoniadis

    2001-06-01

    Full Text Available Wavelet analysis has been found to be a powerful tool for the nonparametric estimation of spatially-variable objects. We discuss in detail wavelet methods in nonparametric regression, where the data are modelled as observations of a signal contaminated with additive Gaussian noise, and provide an extensive review of the vast literature of wavelet shrinkage and wavelet thresholding estimators developed to denoise such data. These estimators arise from a wide range of classical and empirical Bayes methods treating either individual or blocks of wavelet coefficients. We compare various estimators in an extensive simulation study on a variety of sample sizes, test functions, signal-to-noise ratios and wavelet filters. Because there is no single criterion that can adequately summarise the behaviour of an estimator, we use various criteria to measure performance in finite sample situations. Insight into the performance of these estimators is obtained from graphical outputs and numerical tables. In order to provide some hints of how these estimators should be used to analyse real data sets, a detailed practical step-by-step illustration of a wavelet denoising analysis on electrical consumption is provided. Matlab codes are provided so that all figures and tables in this paper can be reproduced.

  12. Performances and Spending Efficiency in Higher Education: A European Comparison through Non-Parametric Approaches

    Science.gov (United States)

    Agasisti, Tommaso

    2011-01-01

    The objective of this paper is an efficiency analysis concerning higher education systems in European countries. Data have been extracted from OECD data-sets (Education at a Glance, several years), using a non-parametric technique--data envelopment analysis--to calculate efficiency scores. This paper represents the first attempt to conduct such an…

  13. Aspects of record linkage

    NARCIS (Netherlands)

    Schraagen, Marijn Paul

    2014-01-01

    This thesis is an exploration of the subject of historical record linkage. The general goal of historical record linkage is to discover relations between historical entities in a database, for any specific definition of relation, entity and database. Although this task originates from historical

  14. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Andersson, Ulf; Perri, Alessandra; Nell, Phillip C.

    2012-01-01

    This paper investigates the pattern of subsidiaries' local vertical linkages under varying levels of competition and subsidiary capabilities. Contrary to most previous literature, we explicitly account for the double role of such linkages as conduits of learning prospects as well as potential...

  15. Analysis of four studies in a comparative framework reveals: health linkage consent rates on British cohort studies higher than on UK household panel surveys.

    Science.gov (United States)

    Knies, Gundi; Burton, Jonathan

    2014-11-27

    A number of cohort studies and longitudinal household panel studies in Great Britain have asked for consent to link survey data to administrative health data. We explore commonalities and differences in the process of collecting consent, achieved consent rates and biases in consent with respect to socio-demographic, socio-economic and health characteristics. We hypothesise that British cohort studies which are rooted within the health sciences achieve higher consent rates than the UK household longitudinal studies which are rooted within the social sciences. By contrast, the lack of a specific health focus in household panel studies means there may be less selectivity in consent, in particular, with respect to health characteristics. Survey designs and protocols for collecting informed consent to health record linkage on two British cohort studies and two UK household panel studies are systematically compared. Multivariate statistical analysis is then performed on information from one cohort and two household panel studies that share a great deal of the data linkage protocol but vary according to study branding, survey design and study population. We find that consent is higher in the British cohort studies than in the UK household panel studies, and is higher the more health-focused the study is. There are no systematic patterns of consent bias across the studies and where effects exist within a study or study type they tend to be small. Minority ethnic groups will be underrepresented in record linkage studies on the basis of all three studies. Systematic analysis of three studies in a comparative framework suggests that the factors associated with consent are idiosyncratic to the study. Analysis of linked health data is needed to establish whether selectivity in consent means the resulting research databases suffer from any biases that ought to be considered.

  16. Of River Linkage and Issue Linkage

    NARCIS (Netherlands)

    Warner, Jeroen Frank

    2016-01-01

    It is a truism in mainstream International Relations that issue linkage promotes regime formation and integration. The present article applies this idea to the transboundary lower river Meuse and finds its history of integration to be a tortuous one. Contextual political factors have at times

  17. 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

  18. Inheritance of 15 microsatellites in the Pacific oyster Crassostrea gigas: segregation and null allele identification for linkage analysis

    Institute of Scientific and Technical Information of China (English)

    LI Li; GUO Ximing; ZHANG Guofan

    2009-01-01

    Microsatellites were screened in a backcross family of the Pacific oyster, Crassostrea gigas. Fifteen microsatellite loci were distinguishable and polymorphic with 6 types of allele-combinations. Null alleles were detected in 46.7% of loci, accounting for 11.7% of the total alleles. Four loci did not segregate in Mendelian Ratios. Three linkage groups were identified among 7 of the 15 segregating loci. Fluorescence-based automated capillary electrophoresis (ABI 310 Genetic Analyzer) that used to detect the microsatellite loci, has been proved a fast, precise, and reliable method in microsatellite genotyping.

  19. A nonparametric and diversified portfolio model

    Science.gov (United States)

    Shirazi, Yasaman Izadparast; Sabiruzzaman, Md.; Hamzah, Nor Aishah

    2014-07-01

    Traditional portfolio models, like mean-variance (MV) suffer from estimation error and lack of diversity. Alternatives, like mean-entropy (ME) or mean-variance-entropy (MVE) portfolio models focus independently on the issue of either a proper risk measure or the diversity. In this paper, we propose an asset allocation model that compromise between risk of historical data and future uncertainty. In the new model, entropy is presented as a nonparametric risk measure as well as an index of diversity. Our empirical evaluation with a variety of performance measures shows that this model has better out-of-sample performances and lower portfolio turnover than its competitors.

  20. Non-Parametric Estimation of Correlation Functions

    DEFF Research Database (Denmark)

    Brincker, Rune; Rytter, Anders; Krenk, Steen

    In this paper three methods of non-parametric correlation function estimation are reviewed and evaluated: the direct method, estimation by the Fast Fourier Transform and finally estimation by the Random Decrement technique. The basic ideas of the techniques are reviewed, sources of bias are pointed...... out, and methods to prevent bias are presented. The techniques are evaluated by comparing their speed and accuracy on the simple case of estimating auto-correlation functions for the response of a single degree-of-freedom system loaded with white noise....

  1. Nonparametric inferences for kurtosis and conditional kurtosis

    Institute of Scientific and Technical Information of China (English)

    XIE Xiao-heng; HE You-hua

    2009-01-01

    Under the assumption of strictly stationary process, this paper proposes a nonparametric model to test the kurtosis and conditional kurtosis for risk time series. We apply this method to the daily returns of S&P500 index and the Shanghai Composite Index, and simulate GARCH data for verifying the efficiency of the presented model. Our results indicate that the risk series distribution is heavily tailed, but the historical information can make its future distribution light-tailed. However the far future distribution's tails are little affected by the historical data.

  2. Preliminary results on nonparametric facial occlusion detection

    Directory of Open Access Journals (Sweden)

    Daniel LÓPEZ SÁNCHEZ

    2016-10-01

    Full Text Available The problem of face recognition has been extensively studied in the available literature, however, some aspects of this field require further research. The design and implementation of face recognition systems that can efficiently handle unconstrained conditions (e.g. pose variations, illumination, partial occlusion... is still an area under active research. This work focuses on the design of a new nonparametric occlusion detection technique. In addition, we present some preliminary results that indicate that the proposed technique might be useful to face recognition systems, allowing them to dynamically discard occluded face parts.

  3. Non-Parametric Bayesian Updating within the Assessment of Reliability for Offshore Wind Turbine Support Structures

    DEFF Research Database (Denmark)

    Ramirez, José Rangel; Sørensen, John Dalsgaard

    2011-01-01

    This work illustrates the updating and incorporation of information in the assessment of fatigue reliability for offshore wind turbine. The new information, coming from external and condition monitoring can be used to direct updating of the stochastic variables through a non-parametric Bayesian...... updating approach and be integrated in the reliability analysis by a third-order polynomial chaos expansion approximation. Although Classical Bayesian updating approaches are often used because of its parametric formulation, non-parametric approaches are better alternatives for multi-parametric updating...... with a non-conjugating formulation. The results in this paper show the influence on the time dependent updated reliability when non-parametric and classical Bayesian approaches are used. Further, the influence on the reliability of the number of updated parameters is illustrated....

  4. NONPARAMETRIC FIXED EFFECT PANEL DATA MODELS: RELATIONSHIP BETWEEN AIR POLLUTION AND INCOME FOR TURKEY

    Directory of Open Access Journals (Sweden)

    Rabia Ece OMAY

    2013-06-01

    Full Text Available In this study, relationship between gross domestic product (GDP per capita and sulfur dioxide (SO2 and particulate matter (PM10 per capita is modeled for Turkey. Nonparametric fixed effect panel data analysis is used for the modeling. The panel data covers 12 territories, in first level of Nomenclature of Territorial Units for Statistics (NUTS, for period of 1990-2001. Modeling of the relationship between GDP and SO2 and PM10 for Turkey, the non-parametric models have given good results.

  5. Construction of a genetic linkage map and QTL analysis for some leaf traits in pear (Pyrus L .)

    Institute of Scientific and Technical Information of China (English)

    Wenying SUN; Yuxing ZHANG; Wenquan LE; Hai'e ZHANG

    2009-01-01

    The major incompatibility barriers to specific inbred lines and the long generation duration in Pyrus L. May hinder the Pyrus breeding process. A genetic linkage map provides the foundation for quantitative trait loci (QTL) mapping and molecular marker-assisted breeding. In this study, we constructed a genetic map with 145 F1 populations from a cross of two cultivars, Yali and Jingbaili, using AFLP and SSR markers. The map consisted of 18 linkage groups which included 402 genetic markers and covered 1395.9 cM, with an average genetic distance of 3.8 cM. The interval mapping was used to identify quantitative trait loci associated with four leaf agronomic traits in the F1 population. The results indicated that four QTLs were associated with leaf length, two QTLs with leaf width, two with leaf length/leaf width, and three with petiole length. The eleven QTLs were associated with 9.9%-48.5% of the phenotypic variation in different traits. It is considered that the map covers almost the whole genome, and molecular markers will be greatly helpful to the related breeding.

  6. Linkage analysis between dominant and co-dominant makers in full-sib families of out-breeding species

    Directory of Open Access Journals (Sweden)

    Alexandre Alonso Alves

    2010-01-01

    Full Text Available As high-throughput genomic tools, such as the DNA microarray platform, have lead to the development of novel genotyping procedures, such as Diversity Arrays Technology (DArT and Single Nucleotide Polymorphisms (SNPs, it is likely that, in the future, high density linkage maps will be constructed from both dominant and co-dominant markers. Recently, a strictly genetic approach was described for estimating recombination frequency (r between co-dominant markers in full-sib families. The complete set of maximum likelihood estimators for r in full-sib families was almost obtained, but unfortunately, one particular configuration involving dominant markers, segregating in a 3:1 ratio and co-dominant markers, was not considered. Here we add nine further estimators to the previously published set, thereby making it possible to cover all combinations of molecular markers with two to four alleles (without epistasis in a full-sib family. This includes segregation in one or both parents, dominance and all linkage phase configurations.

  7. Linkage analysis between dominant and co-dominant makers in full-sib families of out-breeding species.

    Science.gov (United States)

    Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Cruz, Cosme Damião; Alfenas, Acelino Couto

    2010-07-01

    As high-throughput genomic tools, such as the DNA microarray platform, have lead to the development of novel genotyping procedures, such as Diversity Arrays Technology (DArT) and Single Nucleotide Polymorphisms (SNPs), it is likely that, in the future, high density linkage maps will be constructed from both dominant and co-dominant markers. Recently, a strictly genetic approach was described for estimating recombination frequency (r) between co-dominant markers in full-sib families. The complete set of maximum likelihood estimators for r in full-sib families was almost obtained, but unfortunately, one particular configuration involving dominant markers, segregating in a 3:1 ratio and co-dominant markers, was not considered. Here we add nine further estimators to the previously published set, thereby making it possible to cover all combinations of molecular markers with two to four alleles (without epistasis) in a full-sib family. This includes segregation in one or both parents, dominance and all linkage phase configurations.

  8. Development of a molecular genetic linkage map for Colletotrichum lindemuthianum and segregation analysis of two avirulence genes.

    Science.gov (United States)

    Luna-Martínez, Francisco; Rodríguez-Guerra, Raúl; Victoria-Campos, Mayra; Simpson, June

    2007-02-01

    A framework genetic map was developed for the fungal pathogen Colletotrichum lindemuthianum, the causal agent of anthracnose of common bean (Phaseolus vulgaris L.). This is the first genetic map for any species within the family Melanconiaceae and the genus Colletotrichum and provides the first estimate of genome length for C. lindemuthianum. The map was generated using 106 haploid F1 progeny derived from crossing two Mexican C. lindemuthianum isolates differing in two avirulence genes (AvrclMex and AvrclTO). The map comprises 165 AFLP markers covering 1,897 cM with an average spacing of 11.49 cM. The markers are distributed over 19 major linkage groups containing between 5 and 25 markers each and the genome length was estimated to be approximately 3,241 cM. The avirulence genes AvrclMex and AvrclTO segregate in a 1:1 ratio supporting the gene for gene hypothesis for the incompatible reaction between C. lindemuthianum and P. vulgaris, but could not be incorporated into the genetic map. This initial outline map forms the basis for the development of a more detailed C. lindemuthianum linkage map, which would include other types of molecular markers and allow the location of genes previously isolated and characterized in this species.

  9. Review on the Application of Web Linkage-analysis%网络链接分析应用研究综述

    Institute of Scientific and Technical Information of China (English)

    文庭孝; 王尧; 杨雅惟; 刘璇

    2011-01-01

    Web linkage-analysis is an important method in Webometrics research,and it has extensive application.Now Web linkage-analysis was used in following fields: web information resourse assessment,website impact evaluation,university evaluation,discovery of co%网络链接分析法是网络信息计量学研究的重要研究方法,具有广泛的应用。目前国内外主要将网络链接分析方法用于网络信息资源评价、网站网络影响力评价、大学评价、核心网络与核心作者发现、竞争情报与竞争对手分析、网站关联分析、期刊评价以及搜索引擎优化等方面。

  10. Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype.

    Science.gov (United States)

    Khan, A O; Budde, B S; Nürnberg, P; Kawalia, A; Lenzner, S; Bolz, H J

    2017-03-30

    To uncover the genotype underlying early-onset cone-rod dystrophy and central nummular macular atrophic lesion in 2 siblings from an endogamous Arab family, we performed targeted next-generation sequencing (NGS) of 44 retinal dystrophy genes, whole-exome sequencing (WES) and genome-wide linkage analysis. Targeted NGS and WES in the index patient highlighted 2 homozygous variants, a CCDC66 frameshift deletion and a novel missense NMNAT1 variant, c.500G>A (p.Asn167Ser). Linkage and segregation analysis excluded the CCDC66 variant and confirmed the NMNAT1 mutation. Biallelic NMNAT1 mutations cause Leber congenital amaurosis with a central nummular macular atrophic lesion (LCA9). The NMNAT1 mutation reported here underlied cone-rod dystrophy rather than LCA but the fundus lesion was compatible with that of LCA9 patients, highlighting that such a fundus appearance should raise suspicion for biallelic mutations in NMNAT1 when in the context of any retinal dystrophy. Although Ccdc66 mutations have been proposed to cause retinal disease in dogs, our results and public databases challenge CCDC66 as a candidate gene for human retinal dystrophy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Bayesian Nonparametric Clustering for Positive Definite Matrices.

    Science.gov (United States)

    Cherian, Anoop; Morellas, Vassilios; Papanikolopoulos, Nikolaos

    2016-05-01

    Symmetric Positive Definite (SPD) matrices emerge as data descriptors in several applications of computer vision such as object tracking, texture recognition, and diffusion tensor imaging. Clustering these data matrices forms an integral part of these applications, for which soft-clustering algorithms (K-Means, expectation maximization, etc.) are generally used. As is well-known, these algorithms need the number of clusters to be specified, which is difficult when the dataset scales. To address this issue, we resort to the classical nonparametric Bayesian framework by modeling the data as a mixture model using the Dirichlet process (DP) prior. Since these matrices do not conform to the Euclidean geometry, rather belongs to a curved Riemannian manifold,existing DP models cannot be directly applied. Thus, in this paper, we propose a novel DP mixture model framework for SPD matrices. Using the log-determinant divergence as the underlying dissimilarity measure to compare these matrices, and further using the connection between this measure and the Wishart distribution, we derive a novel DPM model based on the Wishart-Inverse-Wishart conjugate pair. We apply this model to several applications in computer vision. Our experiments demonstrate that our model is scalable to the dataset size and at the same time achieves superior accuracy compared to several state-of-the-art parametric and nonparametric clustering algorithms.

  12. Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage

    Science.gov (United States)

    Stuart, P; Nair, R P; Abecasis, G R; Nistor, I; Hiremagalore, R; Chia, N V; Qin, Z S; Thompson, R A; Jenisch, S; Weichenthal, M; Janiga, J; Lim, H W; Christophers, E; Voorhees, J J; Elder, J T

    2006-01-01

    Background A previous study identified two peaks of allelic association between psoriasis and single nucleotide polymorphisms (SNPs) mapping to distal chromosome 17q, including a disease associated SNP that leads to loss of a RUNX1 transcription factor binding site, and additional SNPs in the third intron of the RAPTOR gene. Another study found an association with SNPs in the RAPTOR gene, but not with the RUNX1 binding site polymorphism. Methods In an effort to confirm these observations, we genotyped 579 pedigrees containing 1285 affected individuals for three SNPs immediately flanking and including the RUNX1 binding site, and for three SNPs in the RAPTOR gene. Results Here we report further evidence for linkage to distal chromosome 17q, with a linkage peak mapping 1.7 cM distal to the RUNX1 binding site (logarithm of the odds 2.26 to 2.73, depending upon statistic used). However, we found no evidence for association to individual SNPs or haplotypes in either of the previously identified peaks of association. Power analysis demonstrated 80% power to detect significant association at genotype relative risks of 1.2 (additive and multiplicative models) to 1.5 (dominant and recessive models) for the RUNX1 binding site, and 1.3 to 1.4 for the RAPTOR locus under all models except dominant. Conclusions Our data provide no support for the previously identified RUNX1 binding site or for the RAPTOR locus as genetic determinants of psoriasis, despite evidence for linkage of psoriasis to distal chromosome 17q. PMID:15923274

  13. Using linkage analysis to detect gene-gene interaction by stratifying family data on known disease, or disease-associated, alleles.

    Directory of Open Access Journals (Sweden)

    Barbara Corso

    Full Text Available Detecting gene-gene interaction in complex diseases is a major challenge for common disease genetics. Most interaction detection approaches use disease-marker associations and such methods have low power and unknown reliability in real data. We developed and tested a powerful linkage-analysis-based gene-gene interaction detection strategy based on conditioning the family data on a known disease-causing allele or disease-associated marker allele. We computer-generated multipoint linkage data for a disease caused by two epistatically interacting loci (A and B. We examined several two-locus epistatic inheritance models: dominant-dominant, dominant-recessive, recessive-dominant, recessive-recessive. At one of the loci (A, there was a known disease-related allele. We stratified the family data on the presence of this allele, eliminating family members who were without it. This elimination step has the effect of raising the "penetrance" at the second locus (B. We then calculated the lod score at the second locus (B and compared the pre- and post-stratification lod scores at B. A positive difference indicated interaction. We also examined if it was possible to detect interaction with locus B based on a disease-marker association (instead of an identified disease allele at locus A. We also tested whether the presence of genetic heterogeneity would generate false positive evidence of interaction. The power to detect interaction for a known disease allele was 60-90%. The probability of false positives, based on heterogeneity, was low. Decreasing linkage disequilibrium between the disease and marker at locus A decreased the likelihood of detecting interaction. The allele frequency of the associated marker made little difference to the power.

  14. Analyzing single-molecule time series via nonparametric Bayesian inference.

    Science.gov (United States)

    Hines, Keegan E; Bankston, John R; Aldrich, Richard W

    2015-02-03

    The ability to measure the properties of proteins at the single-molecule level offers an unparalleled glimpse into biological systems at the molecular scale. The interpretation of single-molecule time series has often been rooted in statistical mechanics and the theory of Markov processes. While existing analysis methods have been useful, they are not without significant limitations including problems of model selection and parameter nonidentifiability. To address these challenges, we introduce the use of nonparametric Bayesian inference for the analysis of single-molecule time series. These methods provide a flexible way to extract structure from data instead of assuming models beforehand. We demonstrate these methods with applications to several diverse settings in single-molecule biophysics. This approach provides a well-constrained and rigorously grounded method for determining the number of biophysical states underlying single-molecule data. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Nonparametric estimation of population density for line transect sampling using FOURIER series

    Science.gov (United States)

    Crain, B.R.; Burnham, K.P.; Anderson, D.R.; Lake, J.L.

    1979-01-01

    A nonparametric, robust density estimation method is explored for the analysis of right-angle distances from a transect line to the objects sighted. The method is based on the FOURIER series expansion of a probability density function over an interval. With only mild assumptions, a general population density estimator of wide applicability is obtained.

  16. A non-parametric peak finder algorithm and its application in searches for new physics

    CERN Document Server

    Chekanov, S

    2011-01-01

    We have developed an algorithm for non-parametric fitting and extraction of statistically significant peaks in the presence of statistical and systematic uncertainties. Applications of this algorithm for analysis of high-energy collision data are discussed. In particular, we illustrate how to use this algorithm in general searches for new physics in invariant-mass spectra using pp Monte Carlo simulations.

  17. Analyzing multiple spike trains with nonparametric Granger causality.

    Science.gov (United States)

    Nedungadi, Aatira G; Rangarajan, Govindan; Jain, Neeraj; Ding, Mingzhou

    2009-08-01

    Simultaneous recordings of spike trains from multiple single neurons are becoming commonplace. Understanding the interaction patterns among these spike trains remains a key research area. A question of interest is the evaluation of information flow between neurons through the analysis of whether one spike train exerts causal influence on another. For continuous-valued time series data, Granger causality has proven an effective method for this purpose. However, the basis for Granger causality estimation is autoregressive data modeling, which is not directly applicable to spike trains. Various filtering options distort the properties of spike trains as point processes. Here we propose a new nonparametric approach to estimate Granger causality directly from the Fourier transforms of spike train data. We validate the method on synthetic spike trains generated by model networks of neurons with known connectivity patterns and then apply it to neurons simultaneously recorded from the thalamus and the primary somatosensory cortex of a squirrel monkey undergoing tactile stimulation.

  18. Nonparametric Estimation of Distributions in Random Effects Models

    KAUST Repository

    Hart, Jeffrey D.

    2011-01-01

    We propose using minimum distance to obtain nonparametric estimates of the distributions of components in random effects models. A main setting considered is equivalent to having a large number of small datasets whose locations, and perhaps scales, vary randomly, but which otherwise have a common distribution. Interest focuses on estimating the distribution that is common to all datasets, knowledge of which is crucial in multiple testing problems where a location/scale invariant test is applied to every small dataset. A detailed algorithm for computing minimum distance estimates is proposed, and the usefulness of our methodology is illustrated by a simulation study and an analysis of microarray data. Supplemental materials for the article, including R-code and a dataset, are available online. © 2011 American Statistical Association.

  19. Nonparametric estimation of stochastic differential equations with sparse Gaussian processes

    Science.gov (United States)

    García, Constantino A.; Otero, Abraham; Félix, Paulo; Presedo, Jesús; Márquez, David G.

    2017-08-01

    The application of stochastic differential equations (SDEs) to the analysis of temporal data has attracted increasing attention, due to their ability to describe complex dynamics with physically interpretable equations. In this paper, we introduce a nonparametric method for estimating the drift and diffusion terms of SDEs from a densely observed discrete time series. The use of Gaussian processes as priors permits working directly in a function-space view and thus the inference takes place directly in this space. To cope with the computational complexity that requires the use of Gaussian processes, a sparse Gaussian process approximation is provided. This approximation permits the efficient computation of predictions for the drift and diffusion terms by using a distribution over a small subset of pseudosamples. The proposed method has been validated using both simulated data and real data from economy and paleoclimatology. The application of the method to real data demonstrates its ability to capture the behavior of complex systems.

  20. Nonparametric dark energy reconstruction from supernova data.

    Science.gov (United States)

    Holsclaw, Tracy; Alam, Ujjaini; Sansó, Bruno; Lee, Herbert; Heitmann, Katrin; Habib, Salman; Higdon, David

    2010-12-10

    Understanding the origin of the accelerated expansion of the Universe poses one of the greatest challenges in physics today. Lacking a compelling fundamental theory to test, observational efforts are targeted at a better characterization of the underlying cause. If a new form of mass-energy, dark energy, is driving the acceleration, the redshift evolution of the equation of state parameter w(z) will hold essential clues as to its origin. To best exploit data from observations it is necessary to develop a robust and accurate reconstruction approach, with controlled errors, for w(z). We introduce a new, nonparametric method for solving the associated statistical inverse problem based on Gaussian process modeling and Markov chain Monte Carlo sampling. Applying this method to recent supernova measurements, we reconstruct the continuous history of w out to redshift z=1.5.

  1. Nonparametric k-nearest-neighbor entropy estimator.

    Science.gov (United States)

    Lombardi, Damiano; Pant, Sanjay

    2016-01-01

    A nonparametric k-nearest-neighbor-based entropy estimator is proposed. It improves on the classical Kozachenko-Leonenko estimator by considering nonuniform probability densities in the region of k-nearest neighbors around each sample point. It aims to improve the classical estimators in three situations: first, when the dimensionality of the random variable is large; second, when near-functional relationships leading to high correlation between components of the random variable are present; and third, when the marginal variances of random variable components vary significantly with respect to each other. Heuristics on the error of the proposed and classical estimators are presented. Finally, the proposed estimator is tested for a variety of distributions in successively increasing dimensions and in the presence of a near-functional relationship. Its performance is compared with a classical estimator, and a significant improvement is demonstrated.

  2. Nonparametric estimation of location and scale parameters

    KAUST Repository

    Potgieter, C.J.

    2012-12-01

    Two random variables X and Y belong to the same location-scale family if there are constants μ and σ such that Y and μ+σX have the same distribution. In this paper we consider non-parametric estimation of the parameters μ and σ under minimal assumptions regarding the form of the distribution functions of X and Y. We discuss an approach to the estimation problem that is based on asymptotic likelihood considerations. Our results enable us to provide a methodology that can be implemented easily and which yields estimators that are often near optimal when compared to fully parametric methods. We evaluate the performance of the estimators in a series of Monte Carlo simulations. © 2012 Elsevier B.V. All rights reserved.

  3. Nonparametric Maximum Entropy Estimation on Information Diagrams

    CERN Document Server

    Martin, Elliot A; Meinke, Alexander; Děchtěrenko, Filip; Davidsen, Jörn

    2016-01-01

    Maximum entropy estimation is of broad interest for inferring properties of systems across many different disciplines. In this work, we significantly extend a technique we previously introduced for estimating the maximum entropy of a set of random discrete variables when conditioning on bivariate mutual informations and univariate entropies. Specifically, we show how to apply the concept to continuous random variables and vastly expand the types of information-theoretic quantities one can condition on. This allows us to establish a number of significant advantages of our approach over existing ones. Not only does our method perform favorably in the undersampled regime, where existing methods fail, but it also can be dramatically less computationally expensive as the cardinality of the variables increases. In addition, we propose a nonparametric formulation of connected informations and give an illustrative example showing how this agrees with the existing parametric formulation in cases of interest. We furthe...

  4. Nonparametric estimation of employee stock options

    Institute of Scientific and Technical Information of China (English)

    FU Qiang; LIU Li-an; LIU Qian

    2006-01-01

    We proposed a new model to price employee stock options (ESOs). The model is based on nonparametric statistical methods with market data. It incorporates the kernel estimator and employs a three-step method to modify BlackScholes formula. The model overcomes the limits of Black-Scholes formula in handling option prices with varied volatility. It disposes the effects of ESOs self-characteristics such as non-tradability, the longer term for expiration, the early exercise feature, the restriction on shorting selling and the employee's risk aversion on risk neutral pricing condition, and can be applied to ESOs valuation with the explanatory variable in no matter the certainty case or random case.

  5. On Parametric (and Non-Parametric Variation

    Directory of Open Access Journals (Sweden)

    Neil Smith

    2009-11-01

    Full Text Available This article raises the issue of the correct characterization of ‘Parametric Variation’ in syntax and phonology. After specifying their theoretical commitments, the authors outline the relevant parts of the Principles–and–Parameters framework, and draw a three-way distinction among Universal Principles, Parameters, and Accidents. The core of the contribution then consists of an attempt to provide identity criteria for parametric, as opposed to non-parametric, variation. Parametric choices must be antecedently known, and it is suggested that they must also satisfy seven individually necessary and jointly sufficient criteria. These are that they be cognitively represented, systematic, dependent on the input, deterministic, discrete, mutually exclusive, and irreversible.

  6. Nonparametric inference of network structure and dynamics

    Science.gov (United States)

    Peixoto, Tiago P.

    The network structure of complex systems determine their function and serve as evidence for the evolutionary mechanisms that lie behind them. Despite considerable effort in recent years, it remains an open challenge to formulate general descriptions of the large-scale structure of network systems, and how to reliably extract such information from data. Although many approaches have been proposed, few methods attempt to gauge the statistical significance of the uncovered structures, and hence the majority cannot reliably separate actual structure from stochastic fluctuations. Due to the sheer size and high-dimensionality of many networks, this represents a major limitation that prevents meaningful interpretations of the results obtained with such nonstatistical methods. In this talk, I will show how these issues can be tackled in a principled and efficient fashion by formulating appropriate generative models of network structure that can have their parameters inferred from data. By employing a Bayesian description of such models, the inference can be performed in a nonparametric fashion, that does not require any a priori knowledge or ad hoc assumptions about the data. I will show how this approach can be used to perform model comparison, and how hierarchical models yield the most appropriate trade-off between model complexity and quality of fit based on the statistical evidence present in the data. I will also show how this general approach can be elegantly extended to networks with edge attributes, that are embedded in latent spaces, and that change in time. The latter is obtained via a fully dynamic generative network model, based on arbitrary-order Markov chains, that can also be inferred in a nonparametric fashion. Throughout the talk I will illustrate the application of the methods with many empirical networks such as the internet at the autonomous systems level, the global airport network, the network of actors and films, social networks, citations among

  7. A nonparametric dynamic additive regression model for longitudinal data

    DEFF Research Database (Denmark)

    Martinussen, Torben; Scheike, Thomas H.

    2000-01-01

    dynamic linear models, estimating equations, least squares, longitudinal data, nonparametric methods, partly conditional mean models, time-varying-coefficient models......dynamic linear models, estimating equations, least squares, longitudinal data, nonparametric methods, partly conditional mean models, time-varying-coefficient models...

  8. Nonparametric Bayesian inference for multidimensional compound Poisson processes

    NARCIS (Netherlands)

    S. Gugushvili; F. van der Meulen; P. Spreij

    2015-01-01

    Given a sample from a discretely observed multidimensional compound Poisson process, we study the problem of nonparametric estimation of its jump size density r0 and intensity λ0. We take a nonparametric Bayesian approach to the problem and determine posterior contraction rates in this context, whic

  9. Microsatellite isolation and marker development in carrot - genomic distribution, linkage mapping, genetic diversity analysis and marker transferability across Apiaceae

    Directory of Open Access Journals (Sweden)

    Yildiz Mehtap

    2011-08-01

    Full Text Available Abstract Background The Apiaceae family includes several vegetable and spice crop species among which carrot is the most economically important member, with ~21 million tons produced yearly worldwide. Despite its importance, molecular resources in this species are relatively underdeveloped. The availability of informative, polymorphic, and robust PCR-based markers, such as microsatellites (or SSRs, will facilitate genetics and breeding of carrot and other Apiaceae, including integration of linkage maps, tagging of phenotypic traits and assisting positional gene cloning. Thus, with the purpose of isolating carrot microsatellites, two different strategies were used; a hybridization-based library enrichment for SSRs, and bioinformatic mining of SSRs in BAC-end sequence and EST sequence databases. This work reports on the development of 300 carrot SSR markers and their characterization at various levels. Results Evaluation of microsatellites isolated from both DNA sources in subsets of 7 carrot F2 mapping populations revealed that SSRs from the hybridization-based method were longer, had more repeat units and were more polymorphic than SSRs isolated by sequence search. Overall, 196 SSRs (65.1% were polymorphic in at least one mapping population, and the percentage of polymophic SSRs across F2 populations ranged from 17.8 to 24.7. Polymorphic markers in one family were evaluated in the entire F2, allowing the genetic mapping of 55 SSRs (38 codominant onto the carrot reference map. The SSR loci were distributed throughout all 9 carrot linkage groups (LGs, with 2 to 9 SSRs/LG. In addition, SSR evaluations in carrot-related taxa indicated that a significant fraction of the carrot SSRs transfer successfully across Apiaceae, with heterologous amplification success rate decreasing with the target-species evolutionary distance from carrot. SSR diversity evaluated in a collection of 65 D. carota accessions revealed a high level of polymorphism for these

  10. An estimating function approach to linkage heterogeneity

    Indian Academy of Sciences (India)

    He Gao; Ying Zhou; Weijun Ma; Haidong Liu; Linan Zhao

    2013-12-01

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are four methods (K-test, A-test, B-test and D-test) for testing linkage heterogeneity in linkage analysis, which are based on the likelihood-ratio test. Among them, the commonly used methods are the K-test and A-test. In this paper, we present a novel test method which is different from the above four tests, called G-test. The new test statistic is based on estimating function, possessing a theoretic asymptotic distribution, and therefore demonstrates its own advantages. The proposed test is applied to analyse a real pedigree dataset. Our simulation results also indicate that the G-test performs well in terms of power of testing linkage heterogeneity and outperforms the current methods to some degree.

  11. Construction of a genetic linkage map of Thlaspi caerulescens and quantitative trait loci analysis of zinc accumulation.

    Science.gov (United States)

    Assunção, Ana G L; Pieper, Bjorn; Vromans, Jaap; Lindhout, Pim; Aarts, Mark G M; Schat, Henk

    2006-01-01

    Zinc (Zn) hyperaccumulation seems to be a constitutive species-level trait in Thlaspi caerulescens. When compared under conditions of equal Zn availability, considerable variation in the degree of hyperaccumulation is observed among accessions originating from different soil types. This variation offers an excellent opportunity for further dissection of the genetics of this trait. A T. caerulescens intraspecific cross was made between a plant from a nonmetallicolous accession [Lellingen (LE)], characterized by relatively high Zn accumulation, and a plant from a calamine accession [La Calamine (LC)], characterized by relatively low Zn accumulation. Zinc accumulation in roots and shoots segregated in the F3 population. This population was used to construct an LE/LC amplified fragment length polymorphism (AFLP)-based genetic linkage map and to map quantitative trait loci (QTL) for Zn accumulation. Two QTL were identified for root Zn accumulation, with the trait-enhancing alleles being derived from each of the parents, and explaining 21.7 and 16.6% of the phenotypic variation observed in the mapping population. Future development of more markers, based on Arabidopsis orthologous genes localized in the QTL regions, will allow fine-mapping and map-based cloning of the genes underlying the QTL.

  12. Automation of High-Throughput Mass Spectrometry-Based Plasma N-Glycome Analysis with Linkage-Specific Sialic Acid Esterification.

    Science.gov (United States)

    Bladergroen, Marco R; Reiding, Karli R; Hipgrave Ederveen, Agnes L; Vreeker, Gerda C M; Clerc, Florent; Holst, Stephanie; Bondt, Albert; Wuhrer, Manfred; van der Burgt, Yuri E M

    2015-09-04

    Glycosylation is a post-translational modification of key importance with heterogeneous structural characteristics. Previously, we have developed a robust, high-throughput MALDI-TOF-MS method for the comprehensive profiling of human plasma N-glycans. In this approach, sialic acid residues are derivatized with linkage-specificity, namely the ethylation of α2,6-linked sialic acid residues with parallel lactone formation of α2,3-linked sialic acids. In the current study, this procedure was used as a starting point for the automation of all steps on a liquid-handling robot system. This resulted in a time-efficient and fully standardized procedure with throughput times of 2.5 h for a first set of 96 samples and approximately 1 h extra for each additional sample plate. The mass analysis of the thus-obtained glycans was highly reproducible in terms of relative quantification, with improved interday repeatability as compared to that of manual processing.

  13. Linkage between passenger demand and surrounding land-use patterns at urban rail transit stations: A canonical correlation analysis method and case study in Chongqing

    Directory of Open Access Journals (Sweden)

    Xin Li

    2016-08-01

    Full Text Available This paper employs a canonical correlation analysis method to quantify the linkage between urban rail transit station demand and the surrounding land-use patterns. It is used to identify key land use variables by evaluating their degrees of contribution to the rail transit station demand. A full month of IC card data and detailed regulatory land use plan from Chongqing, China are collected for model development and validation. The proposed model contributes to offering the capability of targeting key land use patterns and associating them with rail transit station boarding and alighting demand simultaneously. The proposed model can reveal underlying rules between rail transit station demand and land use variables and can be used to evaluate the Transit Oriented Development (TOD plans to improve land use and transit operational efficiency.

  14. Interactive Record Linkage

    Directory of Open Access Journals (Sweden)

    2000-12-01

    Full Text Available In order to carry out demographic analyses at individual and group levels, a manual method of linking individual event records from parish registers was developed in the late 1950s. In order to save time and to work with larger areas than small parishes, systems for automatic record linkage were developed a couple of decades later. A third method, an interactive record linkage, named Demolink, has been developed even more recently. The main new feature of the method is the possibility of linking from more than two historical sources simultaneously. This improves the process of sorting out which events belong to which individual life courses. This paper discusses how Demolink was used for record linkage in a large Norwegian parish for the period 1801-1878.

  15. 随机右删失非参数回归模型的影响分析%Influence Analysis of Non-parametric Regression Model with Random Right Censorship

    Institute of Scientific and Technical Information of China (English)

    王淑玲; 冯予; 刘刚

    2012-01-01

    In this paper, the primary model is transformed to non-parametric regression model; Then, local influence is discussed and concise influence matrix is obtained; At last, example is given to illustrate our results.%将随机删失非参数固定设计回归模型转化为非参数回归模型进行研究;然后对此模型作了局部影响分析,得到计算影响矩阵及最大影响曲率方向的简洁公式;最后通过实例分析,验证了分析方法的有效性.

  16. Nonparametric Independence Screening in Sparse Ultra-High Dimensional Additive Models.

    Science.gov (United States)

    Fan, Jianqing; Feng, Yang; Song, Rui

    2011-06-01

    A variable screening procedure via correlation learning was proposed in Fan and Lv (2008) to reduce dimensionality in sparse ultra-high dimensional models. Even when the true model is linear, the marginal regression can be highly nonlinear. To address this issue, we further extend the correlation learning to marginal nonparametric learning. Our nonparametric independence screening is called NIS, a specific member of the sure independence screening. Several closely related variable screening procedures are proposed. Under general nonparametric models, it is shown that under some mild technical conditions, the proposed independence screening methods enjoy a sure screening property. The extent to which the dimensionality can be reduced by independence screening is also explicitly quantified. As a methodological extension, a data-driven thresholding and an iterative nonparametric independence screening (INIS) are also proposed to enhance the finite sample performance for fitting sparse additive models. The simulation results and a real data analysis demonstrate that the proposed procedure works well with moderate sample size and large dimension and performs better than competing methods.

  17. A consensus microsatellite-based linkage map for the hermaphroditic bay scallop (Argopecten irradians and its application in size-related QTL analysis.

    Directory of Open Access Journals (Sweden)

    Hongjun Li

    Full Text Available Bay scallop (Argopecten irradians is one of the most economically important aquaculture species in China. In this study, we constructed a consensus microsatellite-based genetic linkage map with a mapping panel containing two hybrid backcross-like families involving two subspecies of bay scallop, A. i. irradians and A. i. concentricus. One hundred sixty-one microsatellite and one phenotypic (shell color markers were mapped to 16 linkage groups (LGs, which corresponds to the haploid chromosome number of bay scallop. The sex-specific map was 779.2 cM and 781.6 cM long in female and male, respectively, whereas the sex-averaged map spanned 849.3 cM. The average resolution of integrated map was 5.9 cM/locus and the estimated coverage was 81.3%. The proportion of distorted markers occurred more in the hybrid parents, suggesting that the segregation distortion was possibly resulted from heterospecific interaction between genomes of two subspecies of bay scallop. The overall female-to-male recombination rate was 1.13:1 across all linked markers in common to both parents, and considerable differences in recombination also existed among different parents in both families. Four size-related traits, including shell length (SL, shell height (SH, shell width (SW and total weight (TW were measured for quantitative trait loci (QTL analysis. Three significant and six suggestive QTL were detected on five LGs. Among the three significant QTL, two (qSW-10 and qTW-10, controlling SW and TW, respectively were mapped on the same region near marker AiAD121 on LG10 and explained 20.5% and 27.7% of the phenotypic variance, while the third (qSH-7, controlling SH was located on LG7 and accounted for 15.8% of the phenotypic variance. Six suggestive QTL were detected on four different LGs. The linkage map and size-related QTL obtained in this study may facilitate marker-assisted selection (MAS in bay scallop.

  18. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    Science.gov (United States)

    Seshadri, Sudha; DeStefano, Anita L; Au, Rhoda; Massaro, Joseph M; Beiser, Alexa S; Kelly-Hayes, Margaret; Kase, Carlos S; D'Agostino, Ralph B; DeCarli, Charles; Atwood, Larry D; Wolf, Philip A

    2007-01-01

    Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. Results The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously

  19. A Linkage Learning Genetic Algorithm with Linkage Matrix

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The goal of linkage learning, or building block identification, is the creation of a more effective Genetic Algorithm (GA). This paper proposes a new Linkage Learning Genetic Algorithms, named m-LLGA. With the linkage learning module and the linkage-based genetic operation, m-LLGA is not only able to learn and record the linkage information among genes without any prior knowledge of the function being optimized. It also can use the linkage information stored in the linkage matrix to guide the selection of crossover point. The preliminary experiments on two kinds of bounded difficulty problems and a TSP problem validated the performance of m-LLGA. The m-LLGA learns the linkage of different building blocks parallel and therefore solves these problems effectively; it can also reasonably reduce the probability of building blocks being disrupted by crossover at the same time give attention to getting away from local minimum.

  20. Genome-wide linkage analysis of QTL for growth and body composition employing the PorcineSNP60 BeadChip

    Directory of Open Access Journals (Sweden)

    Fernández Ana I

    2012-05-01

    Full Text Available Abstract Background The traditional strategy to map QTL is to use linkage analysis employing a limited number of markers. These analyses report wide QTL confidence intervals, making very difficult to identify the gene and polymorphisms underlying the QTL effects. The arrival of genome-wide panels of SNPs makes available thousands of markers increasing the information content and therefore the likelihood of detecting and fine mapping QTL regions. The aims of the current study are to confirm previous QTL regions for growth and body composition traits in different generations of an Iberian x Landrace intercross (IBMAP and especially identify new ones with narrow confidence intervals by employing the PorcineSNP60 BeadChip in linkage analyses. Results Three generations (F3, Backcross 1 and Backcross 2 of the IBMAP and their related animals were genotyped with PorcineSNP60 BeadChip. A total of 8,417 SNPs equidistantly distributed across autosomes were selected after filtering by quality, position and frequency to perform the QTL scan. The joint and separate analyses of the different IBMAP generations allowed confirming QTL regions previously identified in chromosomes 4 and 6 as well as new ones mainly for backfat thickness in chromosomes 4, 5, 11, 14 and 17 and shoulder weight in chromosomes 1, 2, 9 and 13; and many other to the chromosome-wide signification level. In addition, most of the detected QTLs displayed narrow confidence intervals, making easier the selection of positional candidate genes. Conclusions The use of higher density of markers has allowed to confirm results obtained in previous QTL scans carried out with microsatellites. Moreover several new QTL regions have been now identified in regions probably not covered by markers in previous scans, most of these QTLs displayed narrow confidence intervals. Finally, prominent putative biological and positional candidate genes underlying those QTL effects are listed based on recent porcine

  1. Cosmopolitan linkage disequilibrium maps

    Directory of Open Access Journals (Sweden)

    Gibson Jane

    2005-03-01

    Full Text Available Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD and maps of single nucleotide polymorphisms (SNPs, it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection, the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

  2. 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.

  3. Bayesian nonparametric adaptive control using Gaussian processes.

    Science.gov (United States)

    Chowdhary, Girish; Kingravi, Hassan A; How, Jonathan P; Vela, Patricio A

    2015-03-01

    Most current model reference adaptive control (MRAC) methods rely on parametric adaptive elements, in which the number of parameters of the adaptive element are fixed a priori, often through expert judgment. An example of such an adaptive element is radial basis function networks (RBFNs), with RBF centers preallocated based on the expected operating domain. If the system operates outside of the expected operating domain, this adaptive element can become noneffective in capturing and canceling the uncertainty, thus rendering the adaptive controller only semiglobal in nature. This paper investigates a Gaussian process-based Bayesian MRAC architecture (GP-MRAC), which leverages the power and flexibility of GP Bayesian nonparametric models of uncertainty. The GP-MRAC does not require the centers to be preallocated, can inherently handle measurement noise, and enables MRAC to handle a broader set of uncertainties, including those that are defined as distributions over functions. We use stochastic stability arguments to show that GP-MRAC guarantees good closed-loop performance with no prior domain knowledge of the uncertainty. Online implementable GP inference methods are compared in numerical simulations against RBFN-MRAC with preallocated centers and are shown to provide better tracking and improved long-term learning.

  4. Nonparametric Detection of Geometric Structures Over Networks

    Science.gov (United States)

    Zou, Shaofeng; Liang, Yingbin; Poor, H. Vincent

    2017-10-01

    Nonparametric detection of existence of an anomalous structure over a network is investigated. Nodes corresponding to the anomalous structure (if one exists) receive samples generated by a distribution q, which is different from a distribution p generating samples for other nodes. If an anomalous structure does not exist, all nodes receive samples generated by p. It is assumed that the distributions p and q are arbitrary and unknown. The goal is to design statistically consistent tests with probability of errors converging to zero as the network size becomes asymptotically large. Kernel-based tests are proposed based on maximum mean discrepancy that measures the distance between mean embeddings of distributions into a reproducing kernel Hilbert space. Detection of an anomalous interval over a line network is first studied. Sufficient conditions on minimum and maximum sizes of candidate anomalous intervals are characterized in order to guarantee the proposed test to be consistent. It is also shown that certain necessary conditions must hold to guarantee any test to be universally consistent. Comparison of sufficient and necessary conditions yields that the proposed test is order-level optimal and nearly optimal respectively in terms of minimum and maximum sizes of candidate anomalous intervals. Generalization of the results to other networks is further developed. Numerical results are provided to demonstrate the performance of the proposed tests.

  5. A Comparison of Parametric and Non-Parametric Methods Applied to a Likert Scale.

    Science.gov (United States)

    Mircioiu, Constantin; Atkinson, Jeffrey

    2017-05-10

    A trenchant and passionate dispute over the use of parametric versus non-parametric methods for the analysis of Likert scale ordinal data has raged for the past eight decades. The answer is not a simple "yes" or "no" but is related to hypotheses, objectives, risks, and paradigms. In this paper, we took a pragmatic approach. We applied both types of methods to the analysis of actual Likert data on responses from different professional subgroups of European pharmacists regarding competencies for practice. Results obtained show that with "large" (>15) numbers of responses and similar (but clearly not normal) distributions from different subgroups, parametric and non-parametric analyses give in almost all cases the same significant or non-significant results for inter-subgroup comparisons. Parametric methods were more discriminant in the cases of non-similar conclusions. Considering that the largest differences in opinions occurred in the upper part of the 4-point Likert scale (ranks 3 "very important" and 4 "essential"), a "score analysis" based on this part of the data was undertaken. This transformation of the ordinal Likert data into binary scores produced a graphical representation that was visually easier to understand as differences were accentuated. In conclusion, in this case of Likert ordinal data with high response rates, restraining the analysis to non-parametric methods leads to a loss of information. The addition of parametric methods, graphical analysis, analysis of subsets, and transformation of data leads to more in-depth analyses.

  6. Adaptive Linkage Disequilibrium Between Two Esterase Loci of a Salamander

    Science.gov (United States)

    Webster, T. Preston

    1973-01-01

    In some populations of the salamander Plethodon cinereus, two polymorphic esterase loci are in linkage disequilibrium. Short-term stability of the linkage disequilibrium is demonstrated by an age class analysis. Long, perhaps very long, term stability is suggested by its distribution. This stability and concordant geographic variation in allelic frequencies imply selective origin and maintenance. Data on the frequencies of two color morphs suggest that formation of the linkage disequilibrium is dependent on the genetic background. Images PMID:4515614

  7. A genome-wide search for linkage of estimated glomerular filtration rate (eGFR in the Family Investigation of Nephropathy and Diabetes (FIND.

    Directory of Open Access Journals (Sweden)

    Farook Thameem

    Full Text Available OBJECTIVE: Estimated glomerular filtration rate (eGFR, a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL that influence eGFR. METHODS: Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND study. This study included 954 African Americans (AA, 781 American Indians (AI, 614 European Americans (EA and 1,611 Mexican Americans (MA. A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD formula. RESULTS: The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5 in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4 in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4 at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. CONCLUSION: The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses

  8. Nonparametric Bayesian drift estimation for multidimensional stochastic differential equations

    NARCIS (Netherlands)

    Gugushvili, S.; Spreij, P.

    2014-01-01

    We consider nonparametric Bayesian estimation of the drift coefficient of a multidimensional stochastic differential equation from discrete-time observations on the solution of this equation. Under suitable regularity conditions, we establish posterior consistency in this context.

  9. A non-parametric approach to investigating fish population dynamics

    National Research Council Canada - National Science Library

    Cook, R.M; Fryer, R.J

    2001-01-01

    .... Using a non-parametric model for the stock-recruitment relationship it is possible to avoid defining specific functions relating recruitment to stock size while also providing a natural framework to model process error...

  10. Non-parametric approach to the study of phenotypic stability.

    Science.gov (United States)

    Ferreira, D F; Fernandes, S B; Bruzi, A T; Ramalho, M A P

    2016-02-19

    The aim of this study was to undertake the theoretical derivations of non-parametric methods, which use linear regressions based on rank order, for stability analyses. These methods were extension different parametric methods used for stability analyses and the result was compared with a standard non-parametric method. Intensive computational methods (e.g., bootstrap and permutation) were applied, and data from the plant-breeding program of the Biology Department of UFLA (Minas Gerais, Brazil) were used to illustrate and compare the tests. The non-parametric stability methods were effective for the evaluation of phenotypic stability. In the presence of variance heterogeneity, the non-parametric methods exhibited greater power of discrimination when determining the phenotypic stability of genotypes.

  11. From Enclave to Linkage Economies?

    DEFF Research Database (Denmark)

    Hansen, Michael W.

    and local enterprises by themselves will indeed produce linkages, the scope, depth and development impacts of linkages eventually depend on government intervention. Resource-rich African countries’ governments are aware of this and linkage promotion is increasingly becoming a key element...

  12. Nonparametric Bayesian Modeling for Automated Database Schema Matching

    Energy Technology Data Exchange (ETDEWEB)

    Ferragut, Erik M [ORNL; Laska, Jason A [ORNL

    2015-01-01

    The problem of merging databases arises in many government and commercial applications. Schema matching, a common first step, identifies equivalent fields between databases. We introduce a schema matching framework that builds nonparametric Bayesian models for each field and compares them by computing the probability that a single model could have generated both fields. Our experiments show that our method is more accurate and faster than the existing instance-based matching algorithms in part because of the use of nonparametric Bayesian models.

  13. PV power forecast using a nonparametric PV model

    OpenAIRE

    Almeida, Marcelo Pinho; Perpiñan Lamigueiro, Oscar; Narvarte Fernández, Luis

    2015-01-01

    Forecasting the AC power output of a PV plant accurately is important both for plant owners and electric system operators. Two main categories of PV modeling are available: the parametric and the nonparametric. In this paper, a methodology using a nonparametric PV model is proposed, using as inputs several forecasts of meteorological variables from a Numerical Weather Forecast model, and actual AC power measurements of PV plants. The methodology was built upon the R environment and uses Quant...

  14. A Turkish family with Ellis-van Creveld syndrome in six siblings; linkage analysis on 4p16 region (D4S3360-D4S2366).

    Science.gov (United States)

    Cağdaş, D N; Parlar, A I; Pac, A; Tutun, U; Balci, S

    2008-01-01

    We present a Turkish family and their 6 children, consecutively affected by Ellis-van Creveld (EVC) Syndrome. Four of the affected children died in the postnatal period, and 2 of them had been admitted to the pediatric cardiology department for their cardiologic evaluation. Since they had the features of the EVC Syndrome, linkage analysis was performed with the polymorphic markers, D4S3360-D4S2366, selected from 4p 16 locus. There was complete segregation between the disease and marker allels and the two affected siblings were homozygote for the polymorphic markers, as expected in autosomal recessive inheritance. The diagnosis of EVC Syndrome was confirmed by this molecular analysis. Two cases with EVC were presented in this report. Case 1 had partial abnormal pulmonary venous return and pulmonary stenosis additional to ostium primum atrial septal defect and mitral cleft. Partial abnormal pulmonary venous return and pulmonary stenosis were previously not reported with EVC Syndrome. Postaxial polydactyly phenotype of the Case 2 differs from her brother's. There is bifid 5th metacarpal and unilateral (L) bifid middle and distal phalanges resembling syndactyly.

  15. Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishna, U.; Mehenni, H.; Antonarakis, S.E. [Geneva Medical School (Switzerland)] [and others

    1997-03-01

    Postaxial polydactyly type-A (PAP-A) in humans is an autosomal dominant trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. The extra digit is well formed and articulates with the fifth, or extra, metacarpal/metatarsal, and thus it is usually functional. In order to map the gene responsible for PAP-A, we studied a five-generation Indian family of 37 individuals (15 of whom were affected). A genomewide search with highly informative polymorphic markers on part of the pedigree showed linkage between the PAP-A phenotype and markers on chromosome 7p15-q11.23 (no crossovers were found with D7S526, D7S795, D7S528, D7S521, D7S691, D7S667, D7S478, D7S1830, D7S803, D7S801, or ELN). The highest LOD score was obtained with marker D7S801 (Z{sub max} = 4.21; {theta} = 0). Haplotype analysis enabled the mapping of the PAP-A phenotype in this family between markers D7S2848 and D7S669. Analysis of additional families with PAP-A will narrow down the critical genomic region, facilitate positional cloning of the PAP-A gene, and/or uncover potential genetic heterogeneity. 42 refs., 4 figs., 1 tab.

  16. AN ANALYSIS ON LARGE-SCALE AIR-SEA INTERACTIVE LINKAGES BETWEEN THE TROPICAL INDIAN OCEAN AND THE PACIFIC OCEAN DURING ENSO EVENTS

    Institute of Scientific and Technical Information of China (English)

    DENG Bei-sheng; LIU Hai-tao; CHOU Ji-fan

    2010-01-01

    By utilizing a 3-D atmospheric circulation resolving method, the authors studied the air-sea interactive linkages between the tropical Indian Ocean and the Pacific Ocean in 1979-2008 El Nino-Southern Oscillation (ENSO) events. Their findings showed that evident 3-D gear-coupling characteristics existed in the 1979-2008 ENSO events. Their resolving analyses also suggested that the general circulation showed stronger and wider sinking motions over the eastern Indian Ocean-western Pacific during the mature phase of 1979-2008 ENSO events, compared with the vertical velocities from the U.S. National Centers for Enviornmental Prediction (NCEP) reanalysis data. With their 3-D analysis method, the vertical velocity was resolved by two components, i.e. zonal and meridional components. It was found that the zonal component of the vertical velocities showed a strong sinking motion while the meridional components showed an upward motion during the prevailing phases of the ENSO events,In the tropics, the zonal component of the vertical velocities was found greater than the meridional component, reflecting the dominant characteristics of the vertical velocity, and the overall outcomes showed a strong sinking motion, although the two components also partially offset each other in the processes. Compared with the vertical velocities from NCEP reanalysis, the vertical motions calculated with the 3-D resolving analysis method demonstrate some advantages.

  17. CURRENCY LINKAGES AMONG ASEAN

    OpenAIRE

    CHIN LEE; M. Azali

    2010-01-01

    The purpose of this study is to examine the potential linkages among ASEAN-5 currencies, in particular the possibility of a Singapore dollar bloc during the pre- and post-crisis periods by using the Johansen multivariate cointegration test and the Granger causality test. Significant nonstationarity and the presence of unit roots were documented for each currency under both study periods. Using ASEAN-4 exchange rates against the Singapore dollar, the Johansen cointegration test showed that the...

  18. DPpackage: Bayesian Semi- and Nonparametric Modeling in R

    Directory of Open Access Journals (Sweden)

    Alejandro Jara

    2011-04-01

    Full Text Available Data analysis sometimes requires the relaxation of parametric assumptions in order to gain modeling flexibility and robustness against mis-specification of the probability model. In the Bayesian context, this is accomplished by placing a prior distribution on a function space, such as the space of all probability distributions or the space of all regression functions. Unfortunately, posterior distributions ranging over function spaces are highly complex and hence sampling methods play a key role. This paper provides an introduction to a simple, yet comprehensive, set of programs for the implementation of some Bayesian nonparametric and semiparametric models in R, DPpackage. Currently, DPpackage includes models for marginal and conditional density estimation, receiver operating characteristic curve analysis, interval-censored data, binary regression data, item response data, longitudinal and clustered data using generalized linear mixed models, and regression data using generalized additive models. The package also contains functions to compute pseudo-Bayes factors for model comparison and for eliciting the precision parameter of the Dirichlet process prior, and a general purpose Metropolis sampling algorithm. To maximize computational efficiency, the actual sampling for each model is carried out using compiled C, C++ or Fortran code.

  19. The Utility of Nonparametric Transformations for Imputation of Survey Data

    Directory of Open Access Journals (Sweden)

    Robbins Michael W.

    2014-12-01

    Full Text Available Missing values present a prevalent problem in the analysis of establishment survey data. Multivariate imputation algorithms (which are used to fill in missing observations tend to have the common limitation that imputations for continuous variables are sampled from Gaussian distributions. This limitation is addressed here through the use of robust marginal transformations. Specifically, kernel-density and empirical distribution-type transformations are discussed and are shown to have favorable properties when used for imputation of complex survey data. Although such techniques have wide applicability (i.e., they may be easily applied in conjunction with a wide array of imputation techniques, the proposed methodology is applied here with an algorithm for imputation in the USDA’s Agricultural Resource Management Survey. Data analysis and simulation results are used to illustrate the specific advantages of the robust methods when compared to the fully parametric techniques and to other relevant techniques such as predictive mean matching. To summarize, transformations based upon parametric densities are shown to distort several data characteristics in circumstances where the parametric model is ill fit; however, no circumstances are found in which the transformations based upon parametric models outperform the nonparametric transformations. As a result, the transformation based upon the empirical distribution (which is the most computationally efficient is recommended over the other transformation procedures in practice.

  20. Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21, and 7p in panic disorder families

    Science.gov (United States)

    Logue, M.W.; Bauver, S.R.; Knowles, J.A.; Gameroff, M.J.; Weissman, M.M.; Crowe, R.R.; Fyer, A.J.; Hamilton, S.P.

    2012-01-01

    Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa and the Columba panic disorder families. We use the fuzzy clustering method presented by Kaabi et al. (2006) to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the Iowa families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the Iowa and Columbia datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. PMID:22253211

  1. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  2. Genome-wide linkage analysis of longitudinal phenotypes using sigma(2)(A) random effects (SSARs) fitted by Gibbs sampling

    NARCIS (Netherlands)

    Palmer, LJ; Scurrah, KJ; Tobin, M; Patel, [No Value; Celedon, JC; Burton, PR; Weiss, ST

    2003-01-01

    The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the famili

  3. Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

    NARCIS (Netherlands)

    Duitama, Jorge; Sánchez-Rodríguez, Aminael; Goovaerts, Annelies; Pulido-Tamayo, Sergio; Hubmann, Georg; Foulquié-Moreno, María R.; Thevelein, Johan M.; Verstrepen, Kevin J.; Marchal, Kathleen

    2014-01-01

    Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior p

  4. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

    Directory of Open Access Journals (Sweden)

    Tzur Shay

    2012-10-01

    Full Text Available Abstract Background A recent meta-analysis described a variant (p.Ile2984Val in the cubilin gene (CUBN that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly, and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.

  5. Epithelium-off photochemical corneal collagen cross-linkage using riboflavin and ultraviolet a for keratoconus and keratectasia: a systematic review and meta-analysis.

    Science.gov (United States)

    Craig, Joyce A; Mahon, James; Yellowlees, Ann; Barata, Teresa; Glanville, Julie; Arber, Mick; Mandava, Lakshmi; Powell, John; Figueiredo, Francisco

    2014-07-01

    This report presents the results of a systematic review and meta-analyses of studies on epithelium-off photochemical corneal collagen cross-linkage for the management of keratoconus and secondary ectasia. The literature search identified 3,400 records of which 49 were considered for inclusion in the meta-analyses. Eight papers reported 4 unique randomized controlled trials, 29 studies were prospective, and 12 were retrospective studies. The majority of the studies (39/49) were graded as very low quality evidence. Twenty-six studies described adverse events and were included in the safety analysis. Meta-analyses are presented for changes in four outcomes: visual acuity, topography, refraction and astigmatism, and central corneal thickness. Statistically significant improvements were found in all efficacy outcomes at 12 months after the operation. Common side effects were pain, corneal edema, and corneal haze, which resolved usually within a few days after the procedure. The remaining uncertainty is duration of benefit to establish the procedure's potential benefit in avoiding or delaying disease progression and possibly reducing the need for corneal transplantation.

  6. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  7. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry

    DEFF Research Database (Denmark)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus

    2013-01-01

    from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.......4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and....../or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed...

  8. 非参数回归模型变点两步估计法及实证分析%Two-step change point estimation in nonparametric regression model and the empirical analysis

    Institute of Scientific and Technical Information of China (English)

    赵文芝; 夏志明; 贺飞跃

    2016-01-01

    The two-step estimators for change point in nonparametric regression are proposed.In the first step,an initial estimator is obtained by local linear smoothing method.In the second step,the fi-nal estimator is obtained by CUSUM method on a closed neighborhood of initial estimator.It is found through a simulation study that the proposed estimator is efficient.The estimator for j ump size is also obtained.Further more,experimental results that using historical data on Nile river discharges,ex-change rate data of USD against RMB and global temperature data for the northern hemisphere show that the proposed method is also practical in applications.%针对非参数回归模型变点问题,给出了变点的两步估计方法。第一步,用局部线性方法给出变点的初始估计量;第二步,在初始估计量的邻域内,用 CUSUM方法给出变点的最终估计量,同时获得了变点跃度的估计量。蒙特卡罗随机模拟结果表明了此方法的有效性。最后以尼罗河流量数据,美元兑换人民币汇率数据以及北半球月平均气温数据为例进行分析,结果说明此方法有实际应用价值。

  9. A whole transcriptomal linkage analysis of gene co-regulation in insecticide resistant house flies, Musca domestica

    OpenAIRE

    2013-01-01

    Background Studies suggest that not only is insecticide resistance conferred via multiple gene up-regulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple inse...

  10. Genomewide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12.

    Science.gov (United States)

    Stambolian, Dwight; Ibay, Grace; Reider, Lauren; Dana, Debra; Moy, Chris; Schlifka, Melissa; Holmes, Taura; Ciner, Elise; Bailey-Wilson, Joan E

    2004-09-01

    Mild/moderate (common) myopia is a very common disorder, with both genetic and environmental influences. The environmental factors are related to near work and can be measured. There are no known genetic loci for common myopia. Our goal is to find evidence for a myopia susceptibility gene causing common myopia. Cycloplegic and manifest refraction were performed on 44 large American families of Ashkenazi Jewish descent, each with at least two affected siblings. Individuals with at least -1.00 diopter or lower in each meridian of both eyes were classified as myopic. Microsatellite genotyping with 387 markers was performed by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods by use of 12 different penetrance models. The family-based association test was used for an association scan. A maximum multipoint parametric heterogeneity LOD (HLOD) score of 3.54 was observed at marker D22S685, and nonparametric linkage analyses gave consistent results, with a P value of.0002 at this marker. The parametric multipoint HLOD scores exceeded 3.0 for a 4-cM interval, and significant evidence of genetic heterogeneity was observed. This genomewide scan is the first step toward identifying a gene on chromosome 22 with an influence on common myopia. At present, we are following up our linkage results on chromosome 22 with a dense map of >1,500 single-nucleotide-polymorphism markers for fine mapping and association analyses. Identification of a susceptibility locus in this region may eventually lead to a better understanding of gene-environment interactions in the causation of this complex trait.

  11. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively. Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb. Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

  12. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Science.gov (United States)

    Li, Xin; Hu, Jintian; Zhang, Jiao; Jin, Qian; Wang, Duen-Mei; Yu, Jun; Zhang, Qingguo; Zhang, Yong-Biao

    2014-01-01

    Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean) of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively). Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb). Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

  13. 非参数判别模型%Nonparametric discriminant model

    Institute of Scientific and Technical Information of China (English)

    谢斌锋; 梁飞豹

    2011-01-01

    提出了一类新的判别分析方法,主要思想是将非参数回归模型推广到判别分析中,形成相应的非参数判别模型.通过实例与传统判别法相比较,表明非参数判别法具有更广泛的适用性和较高的回代正确率.%In this paper, the author puts forth a new class of discriminant method, which the main idea is applied non- parametric regression model to discriminant analysis and forms the corresponding nonparametric discriminant model. Compared with the traditional discriminant methods by citing an example, the nonparametric discriminant method has more comprehensive adaptability and higher correct rate of back subsitution.

  14. Floating Car Data Based Nonparametric Regression Model for Short-Term Travel Speed Prediction

    Institute of Scientific and Technical Information of China (English)

    WENG Jian-cheng; HU Zhong-wei; YU Quan; REN Fu-tian

    2007-01-01

    A K-nearest neighbor (K-NN) based nonparametric regression model was proposed to predict travel speed for Beijing expressway. By using the historical traffic data collected from the detectors in Beijing expressways, a specically designed database was developed via the processes including data filtering, wavelet analysis and clustering. The relativity based weighted Euclidean distance was used as the distance metric to identify the K groups of nearest data series. Then, a K-NN nonparametric regression model was built to predict the average travel speeds up to 6 min into the future. Several randomly selected travel speed data series,collected from the floating car data (FCD) system, were used to validate the model. The results indicate that using the FCD, the model can predict average travel speeds with an accuracy of above 90%, and hence is feasible and effective.

  15. A gene-based linkage map for Bicyclus anynana butterflies allows for a comprehensive analysis of synteny with the lepidopteran reference genome.

    Directory of Open Access Journals (Sweden)

    Patrícia Beldade

    2009-02-01

    Full Text Available Lepidopterans (butterflies and moths are a rich and diverse order of insects, which, despite their economic impact and unusual biological properties, are relatively underrepresented in terms of genomic resources. The genome of the silkworm Bombyx mori has been fully sequenced, but comparative lepidopteran genomics has been hampered by the scarcity of information for other species. This is especially striking for butterflies, even though they have diverse and derived phenotypes (such as color vision and wing color patterns and are considered prime models for the evolutionary and developmental analysis of ecologically relevant, complex traits. We focus on Bicyclus anynana butterflies, a laboratory system for studying the diversification of novelties and serially repeated traits. With a panel of 12 small families and a biphasic mapping approach, we first assigned 508 expressed genes to segregation groups and then ordered 297 of them within individual linkage groups. We also coarsely mapped seven color pattern loci. This is the richest gene-based map available for any butterfly species and allowed for a broad-coverage analysis of synteny with the lepidopteran reference genome. Based on 462 pairs of mapped orthologous markers in Bi. anynana and Bo. mori, we observed strong conservation of gene assignment to chromosomes, but also evidence for numerous large- and small-scale chromosomal rearrangements. With gene collections growing for a variety of target organisms, the ability to place those genes in their proper genomic context is paramount. Methods to map expressed genes and to compare maps with relevant model systems are crucial to extend genomic-level analysis outside classical model species. Maps with gene-based markers are useful for comparative genomics and to resolve mapped genomic regions to a tractable number of candidate genes, especially if there is synteny with related model species. This is discussed in relation to the identification of

  16. Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

    Science.gov (United States)

    Cybis, Gabriela B; Sinsheimer, Janet S; Bedford, Trevor; Rambaut, Andrew; Lemey, Philippe; Suchard, Marc A

    2017-01-18

    Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Nonparametric identification of structural modifications in Laplace domain

    Science.gov (United States)

    Suwała, G.; Jankowski, Ł.

    2017-02-01

    This paper proposes and experimentally verifies a Laplace-domain method for identification of structural modifications, which (1) unlike time-domain formulations, allows the identification to be focused on these parts of the frequency spectrum that have a high signal-to-noise ratio, and (2) unlike frequency-domain formulations, decreases the influence of numerical artifacts related to the particular choice of the FFT exponential window decay. In comparison to the time-domain approach proposed earlier, advantages of the proposed method are smaller computational cost and higher accuracy, which leads to reliable performance in more difficult identification cases. Analytical formulas for the first- and second-order sensitivity analysis are derived. The approach is based on a reduced nonparametric model, which has the form of a set of selected structural impulse responses. Such a model can be collected purely experimentally, which obviates the need for design and laborious updating of a parametric model, such as a finite element model. The approach is verified experimentally using a 26-node lab 3D truss structure and 30 identification cases of a single mass modification or two concurrent mass modifications.

  18. Adaptive Neural Network Nonparametric Identifier With Normalized Learning Laws.

    Science.gov (United States)

    Chairez, Isaac

    2016-04-05

    This paper addresses the design of a normalized convergent learning law for neural networks (NNs) with continuous dynamics. The NN is used here to obtain a nonparametric model for uncertain systems described by a set of ordinary differential equations. The source of uncertainties is the presence of some external perturbations and poor knowledge of the nonlinear function describing the system dynamics. A new adaptive algorithm based on normalized algorithms was used to adjust the weights of the NN. The adaptive algorithm was derived by means of a nonstandard logarithmic Lyapunov function (LLF). Two identifiers were designed using two variations of LLFs leading to a normalized learning law for the first identifier and a variable gain normalized learning law. In the case of the second identifier, the inclusion of normalized learning laws yields to reduce the size of the convergence region obtained as solution of the practical stability analysis. On the other hand, the velocity of convergence for the learning laws depends on the norm of errors in inverse form. This fact avoids the peaking transient behavior in the time evolution of weights that accelerates the convergence of identification error. A numerical example demonstrates the improvements achieved by the algorithm introduced in this paper compared with classical schemes with no-normalized continuous learning methods. A comparison of the identification performance achieved by the no-normalized identifier and the ones developed in this paper shows the benefits of the learning law proposed in this paper.

  19. A Non-parametric Approach to Measuring the $k^{-}\\pi^{+}$ Amplitudes in $D^{+} \\to K^{-}K^{+}\\pi{+}$ Decay

    CERN Document Server

    Link, J M; Alimonti, G; Anjos, J C; Arena, V; Barberis, S; Bediaga, I; Benussi, L; Bianco, S; Boca, G; Bonomi, G; Boschini, M; Butler, J N; Carrillo, S; Casimiro, E; Castromonte, C; Cawlfield, C; Cerutti, A; Cheung, H W K; Chiodini, G; Cho, K; Chung, Y S; Cinquini, L; Cuautle, E; Cumalat, J P; D'Angelo, P; Davenport, T F; De Miranda, J M; Di Corato, M; Dini, P; Dos Reis, A C; Edera, L; Engh, D; Erba, S; Fabbri, F L; Frisullo, V; Gaines, I; Garbincius, P H; Gardner, R; Garren, L A; Gianini, G; Gottschalk, E; Göbel, C; Handler, T; Hernández, H; Hosack, M; Inzani, P; Johns, W E; Kang, J S; Kasper, P H; Kim, D Y; Ko, B R; Kreymer, A E; Kryemadhi, A; Kutschke, R; Kwak, J W; Lee, K B; Leveraro, F; Liguori, G; Lopes-Pegna, D; Luiggi, E; López, A M; Machado, A A; Magnin, J; Malvezzi, S; Massafferri, A; Menasce, D; Merlo, M M; Mezzadri, M; Mitchell, R; Moroni, L; Méndez, H; Nehring, M; O'Reilly, B; Otalora, J; Pantea, D; Paris, A; Park, H; Pedrini, D; Pepe, I M; Polycarpo, E; Pontoglio, C; Prelz, F; Quinones, J; Rahimi, A; Ramírez, J E; Ratti, S P; Reyes, M; Riccardi, C; Rovere, M; Sala, S; Segoni, I; Sheaff, M; Sheldon, P D; Stenson, K; Sánchez-Hernández, A; Uribe, C; Vaandering, E W; Vitulo, P; Vázquez, F; Wang, M; Webster, M; Wilson, J R; Wiss, J; Yager, P M; Zallo, A; Zhang, Y

    2007-01-01

    Using a large sample of \\dpkkpi{} decays collected by the FOCUS photoproduction experiment at Fermilab, we present the first non-parametric analysis of the \\kpi{} amplitudes in \\dpkkpi{} decay. The technique is similar to the technique used for our non-parametric measurements of the \\krzmndk{} form factors. Although these results are in rough agreement with those of E687, we observe a wider S-wave contribution for the \\ksw{} contribution than the standard, PDG \\cite{pdg} Breit-Wigner parameterization. We have some weaker evidence for the existence of a new, D-wave component at low values of the $K^- \\pi^+$ mass.

  20. Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.

    Directory of Open Access Journals (Sweden)

    Mine S Cicek

    Full Text Available A substantial proportion of familial colorectal cancer (CRC is not a consequence of known susceptibility loci, such as mismatch repair (MMR genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI-high tumors, or no evidence of linkage to MMR genes. Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR, the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142 and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093. Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively. Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036. These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.

  1. Nonparametric Kernel Smoothing Methods. The sm library in Xlisp-Stat

    Directory of Open Access Journals (Sweden)

    Luca Scrucca

    2001-06-01

    Full Text Available In this paper we describe the Xlisp-Stat version of the sm library, a software for applying nonparametric kernel smoothing methods. The original version of the sm library was written by Bowman and Azzalini in S-Plus, and it is documented in their book Applied Smoothing Techniques for Data Analysis (1997. This is also the main reference for a complete description of the statistical methods implemented. The sm library provides kernel smoothing methods for obtaining nonparametric estimates of density functions and regression curves for different data structures. Smoothing techniques may be employed as a descriptive graphical tool for exploratory data analysis. Furthermore, they can also serve for inferential purposes as, for instance, when a nonparametric estimate is used for checking a proposed parametric model. The Xlisp-Stat version includes some extensions to the original sm library, mainly in the area of local likelihood estimation for generalized linear models. The Xlisp-Stat version of the sm library has been written following an object-oriented approach. This should allow experienced Xlisp-Stat users to implement easily their own methods and new research ideas into the built-in prototypes.

  2. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    Directory of Open Access Journals (Sweden)

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  3. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry.

    Science.gov (United States)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus J; Kozubal, Mark A; Rusch, Douglas B; Tringe, Susannah G; Macur, Richard E; Jennings, Ryan deM; Boyd, Eric S; Spear, John R; Roberto, Francisco F

    2013-01-01

    Geothermal habitats in Yellowstone National Park (YNP) provide an unparalleled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze, and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH). These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high-temperature systems of YNP.

  4. A scoping analysis of peer-reviewed literature about linkages between aquaculture and determinants of human health.

    Science.gov (United States)

    Burns, Theresa E; Wade, Joy; Stephen, Craig; Toews, Lorraine

    2014-06-01

    For many of the world's poor, aquatic products are critical for food security and health. Because the global population is increasing as wild aquatic stocks are declining, aquaculture is an increasingly important source of aquatic products. We undertook a scoping review of the English-language peer-reviewed literature to evaluate how the research community has examined the impacts of aquaculture on four key determinants of human health: poverty, food security, food production sustainability, and gender equality. The review returned 156 primary research articles. Most research (75%) was focused in Asia, with limited research from Africa (10%) and South America (2%). Most research (80%) focused on freshwater finfish and shrimp production. We used qualitative content analysis of records which revealed 11 themes: famer income; the common environment; shared resources; integrated farming/ polyculture; employment; extensive vs. intensive production; local vs. distant ownership; food security; income equity; gender equality; and input costs. We used quantitative content analysis of records and full-text publications about freshwater finfish and shrimp aquaculture to record the frequency with which themes were represented and the positive or negative impacts of aquaculture associated with each theme. Scatter plots showed that no theme was identified in more than half of all articles and publications for both production types. Farmer income was a theme that was identified commonly and was positively impacted by both shrimp and fresh water finfish aquaculture. Polyculture, employment, and local ownership were identified less often as themes, but were also associated with positive impacts. The common environment and shared resources were more common themes in shrimp aquaculture than freshwater finfish aquaculture research, while polyculture and local ownership were more common themes in freshwater finfish aquaculture than shrimp aquaculture. Gender equality, employment, and

  5. 维基百科链接网络实证分析%Structural analysis on Wikipedia linkage network

    Institute of Scientific and Technical Information of China (English)

    王辉; 徐晓旻; 施佺

    2012-01-01

    理解维基百科词条链接网络的结构特征是深入而有效地应用维基百科的前提.基于2010年1月的数据,从度分布、权分布、宏观结构特征等角度对维基百科词条链接网络的结构特征展开实证分析.相关结果与2006年之前的维基百科词条链接网络展开对比,发现当前的维基百科网络仍然具有无标度网络特性;其宏观结构总体上满足bow-tie模型,但模型中的各组成部分比例发生了显著变化.因此,该研究对深入解析维基百科词条链接网络的结构特性具有理论和现实意义.%In order to make better use of Wikipedia, it is necessary to have a clear understanding of the structural features of word entry hyperlink network of Wikipedia. This paper conducted brief experimental analysis in aspects of degree distribution, weight distribution and marco structural analysis on Wikipedia crawled on January 2010. By comparing these characteristic with previous works done before 2006, it found that the Wikipedia hyperlink network still followed power-law distribution on degree and the marco structure still obeyed bow-tie model, however, the proportion of different components defined in bow-tie model varied significantly.

  6. Toward the Integrated Framework Analysis of Linkages among Agrobiodiversity, Livelihood Diversification, Ecological Systems, and Sustainability amid Global Change

    Directory of Open Access Journals (Sweden)

    Karl S. Zimmerer

    2016-04-01

    Full Text Available Scientific and policy interest in the biological diversity of agriculture (agrobiodiversity is expanding amid global socioeconomic and environmental changes and sustainability interests. The majority of global agrobiodiversity is produced in smallholder food-growing. We use meta-analyses in an integrated framework to examine the interactions of smallholder agrobiodiversity with: (1 livelihood processes, especially migration, including impacts on agrobiodiversity as well as the interconnected resource systems of soil, water, and uncultivated habitats; and (2 plant-soil ecological systems. We hypothesize these interactions depend on: (1 scope of livelihood diversification and type resource system; and (2 plant residues and above-/belowground component ecological specificity. Findings show: (1 livelihood diversification is linked to varied environmental factors that range from rampant degradation to enhancing sustainability; and (2 significant ecological coupling of aboveground and soil agrobiodiversity (AGSOBIO assemblages. The environmental impacts of livelihood interactions correspond to variation of diversification (migration, on-farm diversification and resource system (i.e., agrobiodiversity per se, soil, water. Our findings also reveal mutually dependent interactions of aboveground and soil agrobiodiversity. Results identify livelihood diversification-induced reduction of environmental resource quality with lagged agrobiodiversity declines as a potentially major avenue of global change. Our contribution re-frames livelihood interactions to include both agrobiodiversity and ecological systems. We discuss this integrated social-environmental re-framing through the proposed spatial geographic schema of regional agri-food spaces with distinctive matrices of livelihood strategies and relations to biodiversity and resources. This re-framing can be used to integrate livelihood, agrobiodiversity, and ecological analysis and to guide policy and

  7. Linkage of organic anion transporter-1 to metabolic pathways through integrated "omics"-driven network and functional analysis.

    Science.gov (United States)

    Ahn, Sun-Young; Jamshidi, Neema; Mo, Monica L; Wu, Wei; Eraly, Satish A; Dnyanmote, Ankur; Bush, Kevin T; Gallegos, Tom F; Sweet, Douglas H; Palsson, Bernhard Ø; Nigam, Sanjay K

    2011-09-09

    The main kidney transporter of many commonly prescribed drugs (e.g. penicillins, diuretics, antivirals, methotrexate, and non-steroidal anti-inflammatory drugs) is organic anion transporter-1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478). Targeted metabolomics in knockouts have shown that OAT1 mediates the secretion or reabsorption of many important metabolites, including intermediates in carbohydrate, fatty acid, and amino acid metabolism. This observation raises the possibility that OAT1 helps regulate broader metabolic activities. We therefore examined the potential roles of OAT1 in metabolic pathways using Recon 1, a functionally tested genome-scale reconstruction of human metabolism. A computational approach was used to analyze in vivo metabolomic as well as transcriptomic data from wild-type and OAT1 knock-out animals, resulting in the implication of several metabolic pathways, including the citric acid cycle, polyamine, and fatty acid metabolism. Validation by in vitro and ex vivo analysis using Xenopus oocyte, cell culture, and kidney tissue assays demonstrated interactions between OAT1 and key intermediates in these metabolic pathways, including previously unknown substrates, such as polyamines (e.g. spermine and spermidine). A genome-scale metabolic network reconstruction generated some experimentally supported predictions for metabolic pathways linked to OAT1-related transport. The data support the possibility that the SLC22 and other families of transporters, known to be expressed in many tissues and primarily known for drug and toxin clearance, are integral to a number of endogenous pathways and may be involved in a larger remote sensing and signaling system (Ahn, S. Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481-490, and Wu, W., Dnyanmote, A. V., and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795-805). Drugs may alter metabolism by

  8. A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies

    NARCIS (Netherlands)

    Lange, C; Lyon, H; DeMeo, D; Raby, B; Silverman, EK; Weiss, ST

    2003-01-01

    We introduce a new powerful nonparametric testing strategy for family-based association studies in which multiple quantitative traits are recorded and the phenotype with the strongest genetic component is not known prior to the analysis. In the first stage, using a population-based test based on the

  9. Predicting Market Impact Costs Using Nonparametric Machine Learning Models.

    Directory of Open Access Journals (Sweden)

    Saerom Park

    Full Text Available Market impact cost is the most significant portion of implicit transaction costs that can reduce the overall transaction cost, although it cannot be measured directly. In this paper, we employed the state-of-the-art nonparametric machine learning models: neural networks, Bayesian neural network, Gaussian process, and support vector regression, to predict market impact cost accurately and to provide the predictive model that is versatile in the number of variables. We collected a large amount of real single transaction data of US stock market from Bloomberg Terminal and generated three independent input variables. As a result, most nonparametric machine learning models outperformed a-state-of-the-art benchmark parametric model such as I-star model in four error measures. Although these models encounter certain difficulties in separating the permanent and temporary cost directly, nonparametric machine learning models can be good alternatives in reducing transaction costs by considerably improving in prediction performance.

  10. Predicting Market Impact Costs Using Nonparametric Machine Learning Models.

    Science.gov (United States)

    Park, Saerom; Lee, Jaewook; Son, Youngdoo

    2016-01-01

    Market impact cost is the most significant portion of implicit transaction costs that can reduce the overall transaction cost, although it cannot be measured directly. In this paper, we employed the state-of-the-art nonparametric machine learning models: neural networks, Bayesian neural network, Gaussian process, and support vector regression, to predict market impact cost accurately and to provide the predictive model that is versatile in the number of variables. We collected a large amount of real single transaction data of US stock market from Bloomberg Terminal and generated three independent input variables. As a result, most nonparametric machine learning models outperformed a-state-of-the-art benchmark parametric model such as I-star model in four error measures. Although these models encounter certain difficulties in separating the permanent and temporary cost directly, nonparametric machine learning models can be good alternatives in reducing transaction costs by considerably improving in prediction performance.

  11. The properties and mechanism of long-term memory in nonparametric volatility

    Science.gov (United States)

    Li, Handong; Cao, Shi-Nan; Wang, Yan

    2010-08-01

    Recent empirical literature documents the presence of long-term memory in return volatility. But the mechanism of the existence of long-term memory is still unclear. In this paper, we investigate the origin and properties of long-term memory with nonparametric volatility, using high-frequency time series data of the Chinese Shanghai Composite Stock Price Index. We perform Detrended Fluctuation Analysis (DFA) on three different nonparametric volatility estimators with different sampling frequencies. For the same volatility series, the Hurst exponents reduce as the sampling time interval increases, but they are still larger than 1/2, which means that no matter how the interval changes, it still cannot change the existence of long memory. RRV presents a relatively stable property on long-term memory and is less influenced by sampling frequency. RV and RBV have some evolutionary trends depending on time intervals, which indicating that the jump component has no significant impact on the long-term memory property. This suggests that the presence of long-term memory in nonparametric volatility can be contributed to the integrated variance component. Considering the impact of microstructure noise, RBV and RRV still present long-term memory under various time intervals. We can infer that the presence of long-term memory in realized volatility is not affected by market microstructure noise. Our findings imply that the long-term memory phenomenon is an inherent characteristic of the data generating process, not a result of microstructure noise or volatility clustering.

  12. Bayesian Nonparametric Estimation for Dynamic Treatment Regimes with Sequential Transition Times.

    Science.gov (United States)

    Xu, Yanxun; Müller, Peter; Wahed, Abdus S; Thall, Peter F

    2016-01-01

    We analyze a dataset arising from a clinical trial involving multi-stage chemotherapy regimes for acute leukemia. The trial design was a 2 × 2 factorial for frontline therapies only. Motivated by the idea that subsequent salvage treatments affect survival time, we model therapy as a dynamic treatment regime (DTR), that is, an alternating sequence of adaptive treatments or other actions and transition times between disease states. These sequences may vary substantially between patients, depending on how the regime plays out. To evaluate the regimes, mean overall survival time is expressed as a weighted average of the means of all possible sums of successive transitions times. We assume a Bayesian nonparametric survival regression model for each transition time, with a dependent Dirichlet process prior and Gaussian process base measure (DDP-GP). Posterior simulation is implemented by Markov chain Monte Carlo (MCMC) sampling. We provide general guidelines for constructing a prior using empirical Bayes methods. The proposed approach is compared with inverse probability of treatment weighting, including a doubly robust augmented version of this approach, for both single-stage and multi-stage regimes with treatment assignment depending on baseline covariates. The simulations show that the proposed nonparametric Bayesian approach can substantially improve inference compared to existing methods. An R program for implementing the DDP-GP-based Bayesian nonparametric analysis is freely available at https://www.ma.utexas.edu/users/yxu/.

  13. Proteasome modulator 9 gene SNPs, responsible for anti-depressant response, are in linkage with generalized anxiety disorder.

    Science.gov (United States)

    Gragnoli, Claudia

    2014-09-01

    Proteasome modulator 9 (PSMD9) gene single nucleotide polymorphism (SNP) rs1043307/rs2514259 (E197G) is associated with significant clinical response to the anti-depressant desipramine. PSMD9 SNP rs74421874 [intervening sequence (IVS) 3 + nt460 G>A], rs3825172 (IVS3 + nt437 C>T) and rs1043307/rs2514259 (E197G A>G) are all linked to type 2 diabetes (T2D), maturity-onset-diabetes-of the young 3 (MODY3), obesity and waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular and T2D-microvascular disease, T2D-neuropathy, T2D-carpal tunnel syndrome, T2D-nephropathy, T2D-retinopathy, non-diabetic retinopathy and depression. PSMD9 rs149556654 rare SNP (N166S A>G) and the variant S143G A>G also contribute to T2D. PSMD9 is located in the chromosome 12q24 locus, which per se is in linkage with depression, bipolar disorder and anxiety. In the present study, we wanted to determine whether PSMD9 is linked to general anxiety disorder in Italian T2D families. Two-hundred Italian T2D families were phenotyped for generalized anxiety disorder, using the diagnostic criteria of DSM-IV. When the diagnosis was unavailable or unclear, the trait was reported as unknown. The 200 Italians families were tested for the PSMD9 T2D risk SNPs rs74421874 (IVS3 + nt460 G>A), rs3825172 (IVS3 +nt437 T>C) and for the T2D risk and anti-depressant response SNP rs1043307/rs2514259 (E197G A>G) for evidence of linkage with generalized anxiety disorder. Non-parametric linkage analysis was executed via Merlin software. One-thousand simulation tests were performed to exclude results due to random chance. In our study, the PSMD9 gene SNPs rs74421874, rs3825172, and rs1043307/rs2514259 result in linkage to generalized anxiety disorder. This is the first report describing PSMD9 gene SNPs in linkage to generalized anxiety disorder in T2D families.

  14. Nonparametric estimation of a convex bathtub-shaped hazard function.

    Science.gov (United States)

    Jankowski, Hanna K; Wellner, Jon A

    2009-11-01

    In this paper, we study the nonparametric maximum likelihood estimator (MLE) of a convex hazard function. We show that the MLE is consistent and converges at a local rate of n(2/5) at points x(0) where the true hazard function is positive and strictly convex. Moreover, we establish the pointwise asymptotic distribution theory of our estimator under these same assumptions. One notable feature of the nonparametric MLE studied here is that no arbitrary choice of tuning parameter (or complicated data-adaptive selection of the tuning parameter) is required.

  15. Giant cell tumor occurring in familial Paget's disease of bone: report of clinical characteristics and linkage analysis of a large pedigree.

    Science.gov (United States)

    Gianfrancesco, Fernando; Rendina, Domenico; Merlotti, Daniela; Esposito, Teresa; Amyere, Mustapha; Formicola, Daniela; Muscariello, Riccardo; De Filippo, Gianpaolo; Strazzullo, Pasquale; Nuti, Ranuccio; Vikkula, Mikka; Gennari, Luigi

    2013-02-01

    Neoplastic degeneration represents a rare but serious complication of Paget's disease of bone (PDB). Although osteosarcomas have been described in up to 1% of PDB cases, giant cell tumors are less frequent and mainly occur in patients with polyostotic disease. We recently characterized a large pedigree with 14 affected members of whom four developed giant cell tumors at pagetic sites. The high number of affected subjects across multiple generations allowed us to better characterize the clinical phenotype and look for possible susceptibility loci. Of interest, all the affected members had polyostotic PDB, but subjects developing giant cell tumors showed an increased disease severity with a reduced clinical response to bisphosphonate treatment and an increased prevalence of bone pain, deformities, and fractures. Together with an increased occurrence of common pagetic complications, affected patients of this pedigree also evidenced a fivefold higher prevalence of coronary artery disease with respect to either the unaffected family members or a comparative cohort of 150 unrelated PDB cases from the same geographical area. This association was further enhanced in the four cases with PDB and giant cell tumors, all of them developing coronary artery disease before 60 years of age. Despite the early onset and the severe phenotype, PDB patients from this pedigree were negative for the presence of SQSTM1 or TNFRSF11A mutations, previously associated with enhanced disease severity. Genome-wide linkage analysis identified six possible candidate regions on chromosomes 1, 5, 6, 8, 10, and 20. Because the chromosome 8 and 10 loci were next to the TNFRSF11B and OPTN genes, we extended the genetic screening to these two genes, but we failed to identify any causative mutation at both the genomic and transcription level, suggesting that a different genetic defect is associated with PDB and potentially giant cell tumor of bone in this pedigree. Copyright © 2013 American Society for

  16. ANALYSIS OF CONTRIBUTIONS AND LINKAGES

    African Journals Online (AJOL)

    the other hand, Asawase Estate typifies control, rigid and top-down ... Kumasi is the second largest city in Ghana and the estwhile capital of the great ... of clothes and food etc. Currently, most ... photography and dressing making shops. These.

  17. Linkage analysis of bipolar illness with X-chromosome DNA markers: A susceptibility gene in Xq27-q28 cannot be excluded

    Energy Technology Data Exchange (ETDEWEB)

    De bruyn, A.; Raeymaekers, P.; Raes, G. [Univ. of Antwerp (Belgium)] [and others

    1994-12-15

    Transmission studies have supported the presence of a susceptibility gene for bipolar (BP) illness on the X-chromosome. Initial linkage studies with color blindness (CB), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the blood coagulation factor IX (F9) have suggested that a gene for BP illness is located in the Xq27-q28 region. We tested linkage with several DNA markers located in Xq27-q28 in 2 families, MAD3 and MAD4, that previously were linked to F9, and 7 newly ascertained families of BP probands. Linkage was also examined with the gene encoding the {alpha}3 subunit of the gamma-amino butyric acid receptor (GABRA3), a candidate gene for BP illness located in this region. The genetic data were analyzed with the LOD score method using age-dependent penetrance of an autosomal dominant disease gene and narrow and broad clinical models. In MAD3 and MAD4 the multipoint LOD score data suggested a localization of a BPI gene again near F9. In the 7 new families the overall linkage data excluded the Xq27-q28 region. However, if the families were grouped according to their proband`s phenotype BPI or BPII, a susceptibility gene for BPI disorder at the DXS52-F8 cluster could not be excluded. 48 refs., 2 figs., 3 tabs.

  18. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    NARCIS (Netherlands)

    A. González-Neira (Anna); J.M. Rosa-Rosa; A. Osorio (Ana); E. Gonzalez (Emilio); M.C. Southey (Melissa); O. Sinilnikova (Olga); H. Lynch (Henry); R.A. Oldenburg (Rogier); C.J. van Asperen (Christi); N. Hoogerbrugge (Nicoline); G. Pita (G.); P. Devilee (Peter); D. Goldgar (David); J. Benítez (Javier)

    2007-01-01

    textabstractBackground: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BR

  19. Construction of an intra-specific sweet cherry (Prunus avium L.) genetic linkage map and synteny analysis with the Prunus reference map

    Science.gov (United States)

    Linkage maps of the sweet cherry cultivar ‘Emperor Francis’ (EF) and the wild forest cherry ‘New York 54’ (NY) were constructed using primarily simple sequence repeat (SSR) markers and gene-derived markers with known positions on the Prunus reference map. The success rate for identifying SSR markers...

  20. Prenatal diagnosis of the carbohydrate-deficient glycoprotein syndrome type 1A (CDG1A) by a combination of enzymology and genetic linkage analysis after amniocentesis or chorionic villus sampling.

    Science.gov (United States)

    Charlwood, J; Clayton, P; Keir, G; Mian, N; Young, E; Winchester, B

    1998-07-01

    Two pregnancies at risk for the carbohydrate-deficient glycoprotein syndrome Type 1A (CDG1A, phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fetus was predicted in family 1 following amniocentesis. Normal PMM activity was found in cultured amniotic fluid cells and there was no elevation of lysosomal enzymes in the amniotic fluid. Genetic linkage analysis using microsatellite markers closely linked to the CDG1A gene confirmed this prediction. A healthy child was born. In the second family direct assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM was confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combination of biochemical and molecular genetic tests.