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  • Oxford University Press  (29)
  • American Chemical Society (ACS)  (1)
  • Taylor & Francis  (1)
  • 1
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    Testing differential networks with applications to the detection of gene-gene interactions (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-24
    Description: Model organisms and human studies have yielded increasing empirical evidence that interactions among genes contribute broadly to genetic variation of complex traits. In the presence of gene-gene interactions, the dimensionality of the feature space becomes extremely high relative to the sample size. This poses a significant methodological challenge in the identification of gene-gene interactions. In this paper, by using a Gaussian graphical model framework, we translate the problem of identifying gene-gene interactions associated with a binary trait D into an inference problem on the difference of two high-dimensional precision matrices that summarize the conditional dependence network structures of the genes. We propose a procedure for testing the differential network globally, which is particularly powerful against sparse alternatives. In addition, a multiple testing procedure with false discovery rate control is developed to infer the specific structure of the differential network. Theoretical justification is provided to ensure the validity of the proposed tests, and optimality results are derived under sparsity assumptions. Through a simulation study we demonstrate that the proposed tests maintain the desired error rates under the null hypothesis and have good power under the alternative hypothesis. The methods are applied to a breast cancer gene expression study.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 2
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    Dose-effect relationships of nucleoplasmic bridges and complex nuclear anomalies in human peripheral lymphocytes exposed to 60Co {gamma}-rays at a relatively low dose (2016)
    Oxford University Press
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    Publication Date: 2016-06-23
    Description: The dose effect between nucleoplasmic bridges (NPB) and relatively low doses of ionising radiation remains unknown. Accordingly, this study investigated the NPB frequencies in human peripheral blood lymphocytes exposed to low-dose 60 Co -rays. Complex anomalies, including fused nuclei (FUS), horse-shoe nuclei (HS) and circular nuclei (CIR), which possibly originated from multiple NPBs, were also scored. Human peripheral blood samples were collected from three healthy males and irradiated with 0–1 and 0–0.4 Gy 60 Co -rays. A cytokinesis-block micronucleus cytome assay was then conducted to analyse NPB, PFHC (NPB plus three complex nuclear anomalies) and micronucleus (MN) in binucleated cells. All dose–response curves followed the linear model for both NPB frequency and PFHC cell frequency. The dose–response curves between NPB frequency and absorbed dose at 0–1 and 0–0.4 Gy were y = 0.0037 x + 0.0005 ( R 2 = 0.979, P 〈 0.05) and y = 0.0043 x + 0.0004 ( R 2 = 0.941, P 〈 0.05), respectively. The dose–response curves between PFHC cell frequency and absorbed dose at 0–1 and 0–0.4 Gy were y = 0.0044 x + 0.0007 ( R 2 = 0.982, P 〈 0.05) and y = 0.0059 x + 0.0005 ( R 2 = 0.969, P 〈 0.05), respectively. The statistical significance of differences between the irradiated groups (0–0.4 Gy) and background levels of NPB, PFHC and MN were also analysed. The lowest analysable doses of NPB, PFHC and MN were 0.12, 0.08 and 0.08 Gy, respectively. In conclusion, NPBs and PFHC positively correlated with the absorbed radiation at a relatively low dose.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Two novel NAC transcription factors regulate gene expression and flowering time by associating with the histone demethylase JMJ14 (2015)
    Oxford University Press
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    Publication Date: 2015-02-18
    Description: The histone demethylase JMJ14 catalyzes histone demethylation at lysine 4 of histone 3 and is involved in transcriptional repression and flowering time control in Arabidopsis . Here, we report that JMJ14 is physically associated with two previously uncharacterized NAC transcription factors, NAC050 and NAC052. The NAC050/052-RNAi plants and the CRISPR-CAS9-mediated nac050/052 double mutant plants show an early flowering phenotype, which is similar to the phenotype of jmj14 , suggesting a functional association between JMJ14 and NAC050/052. RNA-seq data indicated that hundreds of common target genes are co-regulated by JMJ14 and NAC50/052. Our ChIP analysis demonstrated that JMJ14 and NAC050 directly bind to co-upregulated genes shared in jmj14 and NAC050/052-RNAi , thereby facilitating H3K4 demethylation and transcriptional repression. The NAC050/052 recognition DNA cis-element was identified by an electrophoretic mobility shift assay at the promoters of its target genes. Together, our study identifies two novel NAC transcription repressors and demonstrates that they are involved in transcriptional repression and flowering time control by associating with the histone demethylase JMJ14.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Observation of Surface/Defect States of SnO2 Nanowires on Different Substrates from X-ray Excited Optical Luminescence (2011)
    American Chemical Society (ACS)
    Details
    Publication Date: 2011-12-08
    Description: Crystal Growth & Design DOI: 10.1021/cg2011919
    Print ISSN: 1528-7483
    Electronic ISSN: 1528-7505
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by American Chemical Society (ACS)
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  • 5
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    Covariate-adjusted precision matrix estimation with an application in genetical genomics (2013)
    Oxford University Press
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    Publication Date: 2013-02-24
    Description: Motivated by analysis of genetical genomics data, we introduce a sparse high-dimensional multivariate regression model for studying conditional independence relationships among a set of genes adjusting for possible genetic effects. The precision matrix in the model specifies a covariate-adjusted Gaussian graph, which presents the conditional dependence structure of gene expression after the confounding genetic effects on gene expression are taken into account. We present a covariate-adjusted precision matrix estimation method using a constrained 1 minimization, which can be easily implemented by linear programming. Asymptotic convergence rates in various matrix norms and sign consistency are established for the estimators of the regression coefficients and the precision matrix, allowing both the number of genes and the number of the genetic variants to diverge. Simulation shows that the proposed method results in significant improvements in both precision matrix estimation and graphical structure selection when compared to the standard Gaussian graphical model assuming constant means. The proposed method is applied to yeast genetical genomics data for the identification of the gene network among a set of genes in the mitogen-activated protein kinase pathway.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 6
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    Simultaneous discovery of rare and common segment variants (2013)
    Oxford University Press
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    Publication Date: 2013-02-24
    Description: Copy number variant is an important type of genetic structural variation appearing in germline DNA, ranging from common to rare in a population. Both rare and common copy number variants have been reported to be associated with complex diseases, so it is important to identify both simultaneously based on a large set of population samples. We develop a proportion adaptive segment selection procedure that automatically adjusts to the unknown proportions of the carriers of the segment variants. We characterize the detection boundary that separates the region where a segment variant is detectable by some method from the region where it cannot be detected. Although the detection boundaries are very different for the rare and common segment variants, it is shown that the proposed procedure can reliably identify both whenever they are detectable. Compared with methods for single-sample analysis, this procedure gains power by pooling information from multiple samples. The method is applied to analyse neuroblastoma samples and identifies a large number of copy number variants that are missed by single-sample methods.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 7
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    Variation in water potential, hydraulic characteristics and water source use in montane Douglas-fir and lodgepole pine trees in southwestern Alberta and consequences for seasonal changes in photosynthetic capacity (2012)
    Oxford University Press
    Details
    Publication Date: 2012-03-02
    Description: Tree species response to climate change-induced shifts in the hydrological cycle depends on many physiological traits, particularly variation in water relations characteristics. We evaluated differences in shoot water potential, vulnerability of branches to reductions in hydraulic conductivity, and water source use between Pinus contorta Dougl. ex Loud. var. latifolia Engelm. (lodgepole pine) and Pseudotsuga menziesii (Mirb.) Franco (interior Douglas-fir), and determined the consequences for seasonal changes in photosynthetic capacity. The Douglas-fir site had soil with greater depth, finer texture and higher organic matter content than soil at the lodgepole pine site, all factors that increased the storage of soil moisture. While the measured xylem vulnerability curves were quite similar for the two species, Douglas-fir had lower average midday shoot water potentials than did lodgepole pine. This implied that lodgepole pine exhibited stronger stomatal control of transpiration than Douglas-fir, which helped to reduce the magnitude of the water potential gradient required to access water from drying soil. Stable hydrogen isotope measurements indicated that Douglas-fir increased the use of groundwater during mid-summer when precipitation inputs were low, while lodgepole pine did not. There was a greater reduction of photosynthetic carbon gain in lodgepole pine compared with Douglas-fir when the two tree species were exposed to seasonal declines in soil water content. The contrasting patterns of seasonal variation in photosynthetic capacity observed for the two species were a combined result of differences in soil characteristics at the separate sites and the inherent physiological differences between the species.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Published by Oxford University Press
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  • 8
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    The PRP6-like splicing factor STA1 is involved in RNA-directed DNA methylation by facilitating the production of Pol V-dependent scaffold RNAs (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-08
    Description: DNA methylation is a conserved epigenetic marker in plants and animals. In Arabidopsis , DNA methylation can be established through an RNA-directed DNA methylation (RdDM) pathway. By screening for suppressors of ros1 , we identified STA1, a PRP6-like splicing factor, as a new RdDM regulator. Whole-genome bisulfite sequencing suggested that STA1 and the RdDM pathway share a large number of common targets in the Arabidopsis genome. Small RNA deep sequencing demonstrated that STA1 is predominantly involved in the accumulation of the siRNAs that depend on both Pol IV and Pol V. Moreover, the sta1 mutation partially reduces the levels of Pol V-dependent RNA transcripts. Immunolocalization assay indicated that STA1 signals are exclusively present in the Cajal body and overlap with AGO4 in most nuclei. STA1 signals are also partially overlap with NRPE1. Localization of STA1 to AGO4 and NRPE1 signals is probably related to the function of STA1 in the RdDM pathway. Based on these results, we propose that STA1 acts downstream of siRNA biogenesis and facilitates the production of Pol V-dependent RNA transcripts in the RdDM pathway.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Numerical analysis of non-local convection (2014)
    Oxford University Press
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    Publication Date: 2014-08-13
    Description: In order to examine the numerical instability in 1D non-local turbulent theory, an attempt was made to solve a simplified version of Xiong's non-local turbulent model taking into account the equation of conservation of energy. Using a finite-difference method and staggered grid, the structures of three main configurations of stellar convective zones were calculated. The numerical results show that the convective flux becomes negative and the radiative flux exhibits bumps across the boundaries of the convectively unstable zone. The turbulent velocity decreases rapidly in the upward direction when the pressure decreases to a certain level. In A–F type stars, the convective zones are separated when the temperature gradient is taken as a proxy, but merge when the turbulent velocity is taken as a proxy. The anisotropic treatment of turbulent convection facilitates the non-local effect at the upper boundary of the convection zone.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Optimal stratification in outcome prediction using baseline information (2016)
    Oxford University Press
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    Publication Date: 2016-12-10
    Description: A common practice in predictive medicine is to use current study data to construct a stratification procedure, which groups subjects according to baseline information and forms stratum-specific prevention or intervention strategies. A desirable stratification scheme would not only have small intra-stratum variation but also have a clinically meaningful discriminatory capability. We show how to obtain optimal stratification rules with such desirable properties from fitting a set of regression models relating the outcome to baseline covariates and creating scoring systems for predicting potential outcomes. We propose that all available optimal stratifications be evaluated with an independent dataset to select a final stratification. Lastly, we obtain inferential results for this selected stratification scheme with a holdout dataset. When only one study of moderate size is available, we combine the first two steps via crossvalidation. Extensive simulation studies are used to compare the proposed stratification strategy with alternatives. We illustrate the new proposal using an AIDS clinical trial for binary outcomes and a cardiovascular clinical study for censored event time outcomes.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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