265 research outputs found

    Bayesian Hierarchical Modelling for Two-Dimensional Blood Pressure Data

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    Many real-world phenomena are naturally bivariate. This includes blood pressure, which comprises systolic and diastolic levels. Here, we develop a Bayesian hierarchical model that estimates these values and their interactions simultaneously, using sparse data that vary substantially between groups and over time. A key element of the model is a two-dimensional second-order Intrinsic Gaussian Markov Random Field (IGMRF), which captures non-linear trends in the variables and their interactions. The model is fitted using Markov chain Monte Carlo methods, with a block Metropolis-Hastings algorithm providing efficient updates. Performance is demonstrated using simulated and real data. Furthermore, IGMRFs can be used to induce conditional dependence in Bayesian hierarchical models. IGMRFs have both a precision matrix, which defines the neighbourhood structure of the model, and a precision, or scaling, parameter. Previous studies have shown the importance of selecting the prior of this scaling parameter appropriately for different types of IGMRF, as it can have a substantial impact on posterior results. The focus is on the two-dimensional case, where tuning of the parameter’s prior is achieved by mapping it to the marginal standard deviation of a two-dimensional IGMRF. We compare the effects of scaling various classes of IGMRF, to the application of blood pressure data

    Scaling priors for intrinsic Gaussian Markov random fields applied to blood pressure data

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    An Intrinsic Gaussian Markov Random Field (IGMRF) can be used to induce conditional dependence in Bayesian hierarchical models. IGMRFs have both a precision matrix, which defines the neighborhood structure of the model, and a precision, or scaling, parameter. Previous studies have shown the importance of selecting the prior for this scaling parameter appropriately for different types of IGMRF, as it can have a substantial impact on posterior estimates. Here, we focus on cases in one and two dimensions, where tuning of the prior is achieved by mapping it to the marginal SD of an IGMRF of corresponding dimensionality. We compare the effects of scaling various IGMRFs, including an application to real two‐dimensional blood pressure data using MCMC methods

    A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon

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    Purpose: IFNa was the first cytokine to demonstrate anti-tumor activity in advanced melanoma. Despite the ability of high-dose IFNa reducing relapse and mortality by up to 33%, large majority of patients experience side effects and toxicity which outweigh the benefits. The current study attempts to identify genetic markers likely to be associated with benefit from IFN-a2b treatment and predictive for survival. Experimental design: We tested the association of variants in FOXP3 microsatellites, CTLA4 SNPs and HLA genotype in 284 melanoma patients and their association with prognosis and survival of melanoma patients who received IFNa adjuvant therapy. Results: Univariate survival analysis suggested that patients bearing either the DRB1*15 or HLA-Cw7 allele suffered worse OS while patients bearing either HLA-Cw6 or HLA-B44 enjoyed better OS. DRB1*15 positive patients suffered also worse RFS and conversely HLA-Cw6 positive patients had better RFS. Multivariate analysis revealed that a five-marker genotyping signature was prognostic of OS independent of disease stage. In the multivariate Cox regression model, HLA-B38 (p = 0.021), HLA-C15 (p = 0.025), HLA-C3 (p = 0.014), DRB1*15 (p = 0.005) and CT60*G/G (0.081) were significantly associated with OS with risk ratio of 0.097 (95% CI, 0.013-0.709), 0.387 (95% CI, 0.169-0.889), 0.449 (95% CI, 0.237-0.851), 1.948 (95% CI, 1.221-3.109) and 1.484 (95% IC, 0.953-2.312) respectively. Conclusion: These results suggest that gene polymorphisms relevant to a biological occurrence are more likely to be informative when studied in concert to address potential redundant or conflicting functions that may limit each gene individual contribution. The five markers identified here exemplify this concept though prospective validation in independent cohorts is needed

    The tomato terpene synthase gene family

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    Compounds of the terpenoid class play numerous roles in the interactions of plants with their environment, such as attracting pollinators and defending the plant against pests. We show here that the genome of cultivated tomato (Solanum lycopersicum) contains 44 terpene synthase (TPS) genes, including 29 that are functional or potentially functional. Of these 29 TPS genes, 26 were expressed in at least some organs or tissues of the plant. The enzymatic functions of eight of the TPS proteins were previously reported, and here we report the specific in vitro catalytic activity of 10 additional tomato terpene synthases. Many of the tomato TPS genes are found in clusters, notably on chromosomes 1, 2, 6, 8, and 10. All TPS family clades previously identified in angiosperms are also present in tomato. The largest clade of functional TPS genes found in tomato, with 12 members, is the TPS-a clade, and it appears to encode only sesquiterpene synthases, one of which is localized to the mitochondria, while the rest are likely cytosolic. A few additional sesquiterpene synthases are encoded by TPS-b clade genes. Some of the tomato sesquiterpene synthases use z,z-farnesyl diphosphate in vitro as well, or more efficiently than, the e,e-farnesyl diphosphate substrate. Genes encoding monoterpene synthases are also prevalent, and they fall into three clades: TPS-b, TPS-g, and TPS-e/f. With the exception of two enzymes involved in the synthesis of ent-kaurene, the precursor of gibberellins, no other tomato TPS genes could be demonstrated to encode diterpene synthases so far
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