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  • Articles  (78)
  • Oxford University Press  (78)
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  • Articles  (78)
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  • 1
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    RAPTR-SV: a hybrid method for the detection of structural variants (2015)
    Oxford University Press
    Details
    Publication Date: 2015-06-27
    Description: Motivation: Identification of structural variants (SVs) in sequence data results in a large number of false positive calls using existing software, which overburdens subsequent validation. Results: Simulations using RAPTR-SV and other, similar algorithms for SV detection revealed that RAPTR-SV had superior sensitivity and precision, as it recovered 66.4% of simulated tandem duplications with a precision of 99.2%. When compared with calls made by Delly and LUMPY on available datasets from the 1000 genomes project, RAPTR-SV showed superior sensitivity for tandem duplications, as it identified 2-fold more duplications than Delly, while making ~85% fewer duplication predictions. Availability and implementation: RAPTR-SV is written in Java and uses new features in the collections framework in the latest release of the Java version 8 language specifications. A compiled version of the software, instructions for usage and test results files are available on the GitHub repository page: https://github.com/njdbickhart/RAPTR-SV. Contact : derek.bickhart@ars.usda.gov
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension (2015)
    Oxford University Press
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    Publication Date: 2015-01-13
    Description: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant ( P 〈 5.0 x 10 –8 ) associations with blood pressure, which included variants at three new loci ( CACNA1D , CYP21A2 , and MED13L ) and a newly discovered variant near SLC4A7 . We also replicated 14 previously reported loci, 8 ( CASZ1 , MOV10 , FGF5 , CYP17A1 , SOX6 , ATP2B1 , ALDH2 , and JAG1 ) at genome-wide significance, and 6 ( FIGN , ULK4 , GUCY1A3 , HFE , TBX3-TBX5 , and TBX3 ) at a suggestive level of P = 1.81 x 10 –3 to 5.16 x 10 –8 . These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Stabilization of one-dimensional wave equations coupled with an ODE system on general tree-shaped networks (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-15
    Description: By the theory of Sturm–Liouville eigenvalue problems, it is shown that the stability of one-dimensional wave equations with variable coefficients coupled with an ordinary differential equation (ODE) system on general tree-shaped networks is equivalent to that of its subsystem (called the base system). Thus, it is proved that the coupled system can arrive at asymptotical stability, if, for every interior vertex of the subsystem, the spectra of any two edges joined one common interior vertex of the subsystem are disjoint. Especially, the coupled system with one fixed root is exponentially stable. In the end, a star with three edges and a tree-shaped networks with 10 edges are given to verify the theoretical results.
    Print ISSN: 0265-0754
    Electronic ISSN: 1471-6887
    Topics: Mathematics
    Published by Oxford University Press
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  • 4
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    Forced second-order consensus in directed networks with time delays (2013)
    Oxford University Press
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    Publication Date: 2013-09-18
    Description: This paper investigates the forced second-order consensus problem in directed networks with time delays. First, a general forced consensus protocol is studied and some sufficient and necessary conditions on control parameters are obtained to guarantee the forced consensus; based on these conditions, several convenient methods for choosing parameters are provided. Then, by analysing the poles of the closed-loop system, the delay sensitivity of the protocol is investigated. The maximal upper bound of the allowable delays is provided. Simulation examples are presented to illustrate the effectiveness of the theoretical results.
    Print ISSN: 0265-0754
    Electronic ISSN: 1471-6887
    Topics: Mathematics
    Published by Oxford University Press
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  • 5
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    A study of multifrequency polarization pulse profiles of millisecond pulsars (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-10
    Description: We present high signal-to-noise ratio, multifrequency polarization pulse profiles for 24 millisecond pulsars that are being observed as part of the Parkes Pulsar Timing Array project. The pulsars are observed in three bands, centred close to 730, 1400 and 3100 MHz, using a dual-band 10 cm/50 cm receiver and the central beam of the 20-cm multibeam receiver. Observations spanning approximately six years have been carefully calibrated and summed to produce high S/N profiles. This allows us to study the individual profile components and in particular how they evolve with frequency. We also identify previously undetected profile features. For many pulsars we show that pulsed emission extends across almost the entire pulse profile. The pulse component widths and component separations follow a complex evolution with frequency; in some cases these parameters increase and in other cases they decrease with increasing frequency. The evolution with frequency of the polarization properties of the profile is also non-trivial. We provide evidence that the pre- and post-cursors generally have higher fractional linear polarization than the main pulse. We have obtained the spectral index and rotation measure for each pulsar by fitting across all three observing bands. For the majority of pulsars, the spectra follow a single power-law and the position angles follow a 2 relation, as expected. However, clear deviations are seen for some pulsars. We also present phase-resolved measurements of the spectral index, fractional linear polarization and rotation measure. All these properties are shown to vary systematically over the pulse profile.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    tRF2Cancer: A web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-06
    Description: tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers. The binomial test was introduced to evaluate whether reads from a small RNA-seq data set represent tRFs or degraded fragments. A classification method was then used to annotate the types of tRFs based on their sites of origin in pre-tRNA or mature tRNA. We applied the pipeline to analyze 10 991 data sets from 32 types of cancers and identified thousands of expressed tRFs. A tool called ‘tRFinCancer’ was developed to facilitate the users to inspect the expression of tRFs across different types of cancers. Another tool called ‘tRFBrowser’ shows both the sites of origin and the distribution of chemical modification sites in tRFs on their source tRNA. The tRF2Cancer web server is available at http://rna.sysu.edu.cn/tRFfinder/ .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    O-GlcNAcylation of histone deacetylases 1 in hepatocellular carcinoma promotes cancer progression (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-11
    Description: Hepatocellular carcinoma (HCC) is a malignant tumor originating in the liver. Previous studies have indicated that O-GlcNAc transferase (OGT) and histone deacetylase-1 (HDAC1) play important roles in the pathogenesis of HCC. In the present study, we investigated the physical link between OGT and HDAC1. The O-GlcNAcylation of HDAC1 is overexpressed in HCC. We found that HDAC1 has two major sites of O-GlcNAcylation in its histone deacetylase domain. HDAC1 O-GlcNAcylation increases the activated phosphorylation of HDAC1, which enhances its enzyme activity. HDAC1 O-GlcNAc mutants promote the p21 transcription regulation through affecting the acetylation levels of histones from chromosome, and then influence the proliferation of HCC cells. We also found that mutants of O-GlcNAcylation site of HDAC1 affect invasion and migration of HepG2 cells. E-cadherin level is highly up-regulated in HDAC1 O-GlcNAc mutant-treated liver cancer cells, which inhibit the occurrence and development of HCC. Our findings suggest that OGT promotes the O-GlcNAc modification of HDAC1in the development of HCC. Therefore, inhibiting O-GlcNAcylation of HDAC1 may repress the progression of HCC.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    RCP: a novel probe design bias correction method for Illumina Methylation BeadChip (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-02
    Description: Motivation: The Illumina HumanMethylation450 BeadChip has been extensively utilized in epigenome-wide association studies. This array and its successor, the MethylationEPIC array, use two types of probes—Infinium I (type I) and Infinium II (type II)—in order to increase genome coverage but differences in probe chemistries result in different type I and II distributions of methylation values. Ignoring the difference in distributions between the two probe types may bias downstream analysis. Results: Here, we developed a novel method, called Regression on Correlated Probes (RCP), which uses the existing correlation between pairs of nearby type I and II probes to adjust the beta values of all type II probes. We evaluate the effect of this adjustment on reducing probe design type bias, reducing technical variation in duplicate samples, improving accuracy of measurements against known standards, and retention of biological signal. We find that RCP is statistically significantly better than unadjusted data or adjustment with alternative methods including SWAN and BMIQ. Availability: We incorporated the method into the R package ENmix , which is freely available from the Bioconductor website ( https://www.bioconductor.org/packages/release/bioc/html/ENmix.html ). Contact: niulg@ucmail.uc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 9
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    Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion (2015)
    Oxford University Press
    Details
    Publication Date: 2015-06-24
    Description: With the aim of broadening the versatility of lentiviral vectors as a tool in nucleic acid research, we expanded the genetic code in the propagation of lentiviral vectors for site-specific incorporation of chemical moieties with unique properties. Through systematic exploration of the structure–function relationship of lentiviral VSVg envelope by site-specific mutagenesis and incorporation of residues displaying azide- and diazirine-moieties, the modifiable sites on the vector surface were identified, with most at the PH domain that neither affects the expression of envelope protein nor propagation or infectivity of the progeny virus. Furthermore, via the incorporation of such chemical moieties, a variety of fluorescence probes, ligands, PEG and other functional molecules are conjugated, orthogonally and stoichiometrically, to the lentiviral vector. Using this methodology, a facile platform is established that is useful for tracking virus movement, targeting gene delivery and detecting virus–host interactions. This study may provide a new direction for rational design of lentiviral vectors, with significant impact on both basic research and therapeutic applications.
    Keywords: Cell biology, DNA-Mediated Cell Transformation and Nucleic Acids Transfer
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    A systematic survey of the Cys2His2 zinc finger DNA-binding landscape (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-18
    Description: Cys 2 His 2 zinc fingers (C2H2-ZFs) comprise the largest class of metazoan DNA-binding domains. Despite this domain's well-defined DNA-recognition interface, and its successful use in the design of chimeric proteins capable of targeting genomic regions of interest, much remains unknown about its DNA-binding landscape. To help bridge this gap in fundamental knowledge and to provide a resource for design-oriented applications, we screened large synthetic protein libraries to select binding C2H2-ZF domains for each possible three base pair target. The resulting data consist of 〉160 000 unique domain–DNA interactions and comprise the most comprehensive investigation of C2H2-ZF DNA-binding interactions to date. An integrated analysis of these independent screens yielded DNA-binding profiles for tens of thousands of domains and led to the successful design and prediction of C2H2-ZF DNA-binding specificities. Computational analyses uncovered important aspects of C2H2-ZF domain–DNA interactions, including the roles of within-finger context and domain position on base recognition. We observed the existence of numerous distinct binding strategies for each possible three base pair target and an apparent balance between affinity and specificity of binding. In sum, our comprehensive data help elucidate the complex binding landscape of C2H2-ZF domains and provide a foundation for efforts to determine, predict and engineer their DNA-binding specificities.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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