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Phenotypes measured in counts are commonly observed in nature. Statistical methods for mapping quantitative trait loci (QTL) underlying count traits are documented in the literature. The majority of them assume that the count phenotype follows a Poisson distribution with appropriate techniques being applied to handle data dispersion. When a count trait has a genetic basis, “naturally occurring” zero status also reflects the underlying gene effects. Simply ignoring or miss-handling the zero data may lead to wrong QTL inference. In this article, we propose an interval mapping approach for mapping QTL underlying count phenotypes containing many zeros. The effects of QTLs on the zero-inflated count trait are modelled through the zero-inflated generalized Poisson regression mixture model, which can handle the zero inflation and Poisson dispersion in the same distribution. We implement the approach using the EM algorithm with the Newton-Raphson algorithm embedded in the M-step, and provide a genome-wide scan for testing and estimating the QTL effects. The performance of the proposed method is evaluated through extensive simulation studies. Extensions to composite and multiple interval mapping are discussed. The utility of the developed approach is illustrated through a mouse F2 intercross data set. Significant QTLs are detected to control mouse cholesterol gallstone formation. 相似文献
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目的 通过观察MAN2C1转基因小鼠对H5N1高致病性禽流感病毒的易感性,以了解此转基因小鼠的免疫应答情况和MAN2C1基因在病毒感染中的作用。方法 以H5N1高致病性禽流感病毒滴鼻感染MAN2C1转基因小鼠,HE染色观察小鼠肺组织病理变化;RT-PCR和免疫组织化学方法检测小鼠肺组织H5N1病毒载量;间接ELISA方法 检测小鼠血清抗体滴度变化。结果 与对照组小鼠比较,MAN2C1转基因小鼠表现为更为严重的间质性肺炎,肺组织病毒载量增加,外周血中性粒细胞数目降低,淋巴细胞数量增加,血清IgG抗体滴度降低。结论 MAN2C1基因抑制了小鼠的体液免疫。 相似文献
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Marcos O. Prates Robert H. Aseltine Jr. Dipak K. Dey Jun Yan 《Biometrical journal. Biometrische Zeitschrift》2013,55(6):912-924
Unhealthy alcohol use is one of the leading causes of morbidity and mortality in the United States. Brief interventions with high‐risk drinkers during an emergency department (ED) visit are of great interest due to their possible efficacy and low cost. In a collaborative study with patients recruited at 14 academic ED across the United States, we examined the self‐reported number of drinks per week by each patient following the exposure to a brief intervention. Count data with overdispersion have been mostly analyzed with generalized linear mixed models (GLMMs), of which only a limited number of link functions are available. Different choices of link function provide different fit and predictive power for a particular dataset. We propose a class of link functions from an alternative way to incorporate random effects in a GLMM, which encompasses many existing link functions as special cases. The methodology is naturally implemented in a Bayesian framework, with competing links selected with Bayesian model selection criteria such as the conditional predictive ordinate (CPO). In application to the ED intervention study, all models suggest that the intervention was effective in reducing the number of drinks, but some new models are found to significantly outperform the traditional model as measured by CPO. The validity of CPO in link selection is confirmed in a simulation study that shared the same characteristics as the count data from high‐risk drinkers. The dataset and the source code for the best fitting model are available in Supporting Information. 相似文献
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We describe a method for modeling carcinogenicity from animal studies where the data consist of counts of the number of tumors present over time. The research is motivated by applications to transgenic rodent studies, which have emerged as an alternative to chronic bioassays for screening possible carcinogens. In transgenic mouse studies, the endpoint of interest is frequently skin papilloma, with weekly examinations determining how many papillomas each animal has at a particular point in time. It is assumed that each animal has two unobservable latent variables at each time point. The first indicates whether or not the tumors are in a multiplying state and the second is the potential number of additional tumors if the tumors are in a multiplying state. The product of these variables follows a zero-inflated Poisson distribution, and the EM algorithm can be used to maximize the observed-data pseudo-likelihood, based on the latent variables. A generalized estimating equations robust variance estimator adjusts for dependency among outcomes within individual animals. The method is applied to testing for a dose-related trend in both tumor incidence and multiplicity in carcinogenicity studies. 相似文献
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Summary As most georeferenced data sets are multivariate and concern variables of different types, spatial mapping methods must be able to deal with such data. The main difficulties are the prediction of non‐Gaussian variables and the modeling of the dependence between processes. The aim of this article is to present a new hierarchical Bayesian approach that permits simultaneous modeling of dependent Gaussian, count, and ordinal spatial fields. This approach is based on spatial generalized linear mixed models. We use a moving average approach to model the spatial dependence between the processes. The method is first validated through a simulation study. We show that the multivariate model has better predictive abilities than the univariate one. Then the multivariate spatial hierarchical model is applied to a real data set collected in French Guiana to predict topsoil patterns. 相似文献
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689 boys and 644 girls of a northern Greek children population have been studied concerning the head and face shape by means of principal component analysis. From the morphological patterns show a homogenic population with small shape differences due mainly to vertical and ear variables. Size differences appear to be responsible for the variability of the population. 相似文献
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Katiane S. Conceição Marinho G. Andrade Francisco Louzada 《Biometrical journal. Biometrische Zeitschrift》2013,55(5):661-678
In this paper, a Bayesian method for inference is developed for the zero‐modified Poisson (ZMP) regression model. This model is very flexible for analyzing count data without requiring any information about inflation or deflation of zeros in the sample. A general class of prior densities based on an information matrix is considered for the model parameters. A sensitivity study to detect influential cases that can change the results is performed based on the Kullback–Leibler divergence. Simulation studies are presented in order to illustrate the performance of the developed methodology. Two real datasets on leptospirosis notification in Bahia State (Brazil) are analyzed using the proposed methodology for the ZMP model. 相似文献
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A群及C群流脑多糖抗原用 10 0 0 0 0×g离心或不经超速离心处理 ,经用鲎试验法测定内毒素含量 ,2种工艺生产的A群及C群流脑多糖抗原的内毒素含量均很低。用未经超速离心处理的A群及C群流脑多糖抗原制成的A C群流脑多糖菌苗 ,经鲎试验法测定 ,内毒素含量也很低 ;经家兔升温法进行热原质试验 ,家兔体温未明显升高。证明A C群流脑多糖菌苗生产工艺不经 10 0 0 0 0×g离心去除内毒素步骤是可行的。所制备的流脑多糖抗原内毒素含量符合要求。 相似文献
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The combination of redox potentiometry with low temperature electron spin resonance (ESR) spectroscopy has led to further characterization of electron transfer components of Chromatium D. These include the readily buffer-soluble cytochromes c553 and c′ and the high-potential iron-sulfur protein in the isolated state and associated with the chromatophore membrane. Buffer-insoluble cytochrome c553, cytochro—me c555, bacteriochlorophyll and the primary electron acceptor have been characterized both in the chromatophore membrane and also in a sodium dodecylsulfate detergent-solubilized subchromatophore preparation. Two iron-sulfur proteins have been revealed which are present in the chromatophore membrane but are released on treatment with sodium dodecylsulfate. They have central g values at 1.90 and 1.94 and have estimated midpoint potentials at pH 7.4 (Em7·4) at +280 mV and ?100 mV, respectively, when associated with the chromatophore.In the membrane associated state the apparent Em of cytochrome c′ is approximately 200 mV more positive than the Em values reported for the free state; this implies either that the reduced form of cytochrome c′ binds to the membrane (or to a component therein) to a degree which is > 103 times greater than that of the oxidized form or that the Em shift results from membrane solvation. In the case of the high-potential iron-sulfur protein however, its Em when associated with the chromatophore membrane is similar to that reported in the isolated state. The light-induced oxidation of the high-potential iron-sulfur protein at room temperature appears to be linked only to the oxidation of cytochrome c555; it could serve as an electron pool in equilibrium with cytochrome c555 in the cyclic electron flow system.The redox component defined in the reduced state by its gy = 1.82 and gx = 1.62 ESR spectrum satisfies the following criteria for its identification as the primary electron acceptor of P883. (a) The Em7·4 value of the g = 1.82 component is ?120 ± 25mV. (b) At ?70 mV, where the g = 1.82 component is mainly oxidized in the dark, brief illumination at low temperature which causes the irreversible oxidation of one cytochrome c553 heme, also induces the permanent reduction of the g = 1.82 component; the extent of reduction after brief illumination, given by the g = 1.82 signal height, is the same as that induced chemically at ?270 mV showing it to be fully reduced by the receipt of a single electron. (c) At more positive potentials where cytochrome c553 is oxidized and is not involved in low-temperature reactions, the light-induced low-temperature kinetics of the g = 1.82 signal are reversible; the flash-induced g = 1.82 formation and subsequent dark decay are the same as those for the flash-induced P+883 (g = 2) formation and dark decay. We suggest that until a full physical-chemical characterization is completed this g = 1.82 component be designated “photoredoxin”. 相似文献
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八角属(八角科)三种植物之小记 总被引:3,自引:3,他引:3
根据对腊叶标本的研究,将少药八角Illicium oligandrum Merrill & Chun、I. parvifolium Merrill subsp. oligandrum(Merrill & Chun)Q. Lin作为小叶八角I. parvifolium Merrill的新异名,将苏门答腊八角I. sumatranum A. C. Smith作为里德利八角I. ridleyanum A. C. Smith的新异名,发现厚皮香八角I. ternstroemioides A. C. Smith在越南的新记录。 相似文献
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A fundamental methodology in neurophysiology involves recording the electrical signals associated with individual neurons within brains of awake behaving animals. Traditional statistical analyses have relied mainly on mean firing rates over some epoch (often several hundred milliseconds) that are compared across experimental conditions by analysis of variance. Often, however, the time course of the neuronal firing patterns is of interest, and a more refined procedure can produce substantial additional information. In this paper we compare neuronal firing in the supplementary eye field of a macaque monkey across two experimental conditions. We take the electrical discharges, or 'spikes', to be arrivals in a inhomogeneous Poisson process and then model the firing intensity function using both a simple parametric form and more flexible splines. Our main interest is in making inferences about certain characteristics of the intensity, including the timing of the maximal firing rate. We examine data from 84 neurons individually and also combine results into a hierarchical model. We use Bayesian estimation methods and frequentist significance tests based on a nonparametric bootstrap procedure. We are thereby able to conclude that a substantial fraction of the neurons exhibit important temporal differences in firing intensity across the two conditions, and we quantify the effect across the population of neurons. 相似文献
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G. Savitha D. Leonidas K. R. Acharya M. A. Viswamitra 《Acta Crystallographica. Section D, Structural Biology》2001,57(6):873-875
Repeat units based on the telomeric sequence of the ciliated protozoan Tetrahymena, d(C4A2)2, have been crystallized. Cytosine‐rich DNA stretches are known to reside in telomeres and centromeres of eukaryotic chromosomes, playing crucial roles in the structural stability of the chromosome in addition to their connection with cancer and aging. Preliminary investigations on the telomeric repeat sequence C4A2C4A2 from CD studies and X‐ray crystal data suggest it to be a right‐handed interdigitated tetraplex structure with hemiprotonated C·C+ base pairs. The molecules appear to be packed one on top of another forming a discontinuous helix along c simulating a poly‐C fibre, an arrangement which maximizes the number of cytosines stacked. 相似文献
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Marianna Biadene Pierre Montaville George M. Sheldrick Stefan Becker 《Acta Crystallographica. Section D, Structural Biology》2006,62(7):793-799
Rabphilin‐3A is a neuronal protein containing a C2‐domain tandem. To date, only the structure of the C2B domain has been solved. The crystal structure of the Ca2+‐free C2A domain has been solved by molecular replacement and refined to 1.92 Å resolution. It adopts the classical C2‐domain fold consisting of an eight‐stranded antiparallel β‐sandwich with type I topology. In agreement with its Ca2+‐dependent negatively charged membrane‐binding properties, this C2 domain contains all the conserved acidic residues responsible for calcium binding. However, the replacement of a conserved aspartic acid residue by glutamic acid allows formation of an additional strong hydrogen bond, resulting in increased rigidity of calcium‐binding loop 1. The electrostatic surface of the C2A domain consists of a large positively charged belt surrounded by two negatively charged patches located at both tips of the domain. In comparison, the structurally very similar C2A domain of synaptotagmin I has a highly acidic electrostatic surface, suggesting completely unrelated functions for these two C2A domains. 相似文献