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The UCSC Genome Browser database: extensions and updates 2013 (2012)

Meyer, L. R., Zweig, A. S., Hinrichs, A. S., Karolchik, D., Kuhn, R. M., Wong, M., Sloan, C. A., Rosenbloom, K. R., Roe, G., Rhead, B., Raney, B. J., Pohl, A., Malladi, V. S., Li, C. H., Lee, B. T., Learned, K., Kirkup, V., Hsu, F., Heitner, S., Harte, R. A., Haeussler, M., Guruvadoo, L., Goldman, M., Giardine, B. M., Fujita, P. A., Dreszer, T. R., Diekhans, M., Cline, M. S., Clawson, H., Barber, G. P., Haussler, D., Kent, W. J.

Oxford University Press

In: Nucleic Acids Research

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Publikationsdatum: 2012-12-20

Beschreibung: The University of California Santa Cruz (UCSC) Genome Browser ( http://genome.ucsc.edu ) offers online public access to a growing database of genomic sequence and annotations for a wide variety of organisms. The Browser is an integrated tool set for visualizing, comparing, analysing and sharing both publicly available and user-generated genomic datasets. As of September 2012, genomic sequence and a basic set of annotation ‘tracks’ are provided for 63 organisms, including 26 mammals, 13 non-mammal vertebrates, 3 invertebrate deuterostomes, 13 insects, 6 worms, yeast and sea hare. In the past year 19 new genome assemblies have been added, and we anticipate releasing another 28 in early 2013. Further, a large number of annotation tracks have been either added, updated by contributors or remapped to the latest human reference genome. Among these are an updated UCSC Genes track for human and mouse assemblies. We have also introduced several features to improve usability, including new navigation menus. This article provides an update to the UCSC Genome Browser database, which has been previously featured in the Database issue of this journal.

Print ISSN: 0305-1048

Digitale ISSN: 1362-4962

Thema: Biologie

Publiziert von Oxford University Press

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Mitochondrial dynamics and autophagy aid in removal of persistent mitochondrial DNA damage in Caenorhabditis elegans (2012)

Bess, A. S., Crocker, T. L., Ryde, I. T., Meyer, J. N.

Oxford University Press

In: Nucleic Acids Research

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Publikationsdatum: 2012-09-13

Beschreibung: Mitochondria lack the ability to repair certain helix-distorting lesions that are induced at high levels in mitochondrial DNA (mtDNA) by important environmental genotoxins and endogenous metabolites. These lesions are irreparable and persistent in the short term, but their long-term fate is unknown. We report that removal of such mtDNA damage is detectable by 48 h in Caenorhabditis elegans , and requires mitochondrial fusion, fission and autophagy, providing genetic evidence for a novel mtDNA damage removal pathway. Furthermore, mutations in genes involved in these processes as well as pharmacological inhibition of autophagy exacerbated mtDNA damage-mediated larval arrest, illustrating the in vivo relevance of removal of persistent mtDNA damage. Mutations in genes in these pathways exist in the human population, demonstrating the potential for important gene–environment interactions affecting mitochondrial health after genotoxin exposure.

Print ISSN: 0305-1048

Digitale ISSN: 1362-4962

Thema: Biologie

Publiziert von Oxford University Press

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R-CHIE: a web server and R package for visualizing RNA secondary structures (2012)

Lai, D., Proctor, J. R., Zhu, J. Y. A., Meyer, I. M.

Oxford University Press

In: Nucleic Acids Research

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Publikationsdatum: 2012-06-28

Beschreibung: Visually examining RNA structures can greatly aid in understanding their potential functional roles and in evaluating the performance of structure prediction algorithms. As many functional roles of RNA structures can already be studied given the secondary structure of the RNA, various methods have been devised for visualizing RNA secondary structures. Most of these methods depict a given RNA secondary structure as a planar graph consisting of base-paired stems interconnected by roundish loops. In this article, we present an alternative method of depicting RNA secondary structure as arc diagrams. This is well suited for structures that are difficult or impossible to represent as planar stem-loop diagrams. Arc diagrams can intuitively display pseudo-knotted structures, as well as transient and alternative structural features. In addition, they facilitate the comparison of known and predicted RNA secondary structures. An added benefit is that structure information can be displayed in conjunction with a corresponding multiple sequence alignments, thereby highlighting structure and primary sequence conservation and variation. We have implemented the visualization algorithm as a web server R- chie as well as a corresponding R package called R4RNA, which allows users to run the software locally and across a range of common operating systems.

Schlagwort(e): Nucleic acid structure, Computational Methods

Print ISSN: 0305-1048

Digitale ISSN: 1362-4962

Thema: Biologie

Publiziert von Oxford University Press

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Computational inference of mRNA stability from histone modification and transcriptome profiles (2012)

Wang, C., Tian, R., Zhao, Q., Xu, H., Meyer, C. A., Li, C., Zhang, Y., Liu, X. S.

Oxford University Press

In: Nucleic Acids Research

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Publikationsdatum: 2012-08-08

Beschreibung: Histone modifications play important roles in regulating eukaryotic gene expression and have been used to model expression levels. Here, we present a regression model to systematically infer mRNA stability by comparing transcriptome profiles with ChIP-seq of H3K4me3, H3K27me3 and H3K36me3. The results from multiple human and mouse cell lines show that the inferred unstable mRNAs have significantly longer 3'Untranslated Regions (UTRs) and more microRNA binding sites within 3'UTR than the inferred stable mRNAs. Regression residuals derived from RNA-seq, but not from GRO-seq, are highly correlated with the half-lives measured by pulse-labeling experiments, supporting the rationale of our inference. Whereas, the functions enriched in the inferred stable and unstable mRNAs are consistent with those from pulse-labeling experiments, we found the unstable mRNAs have higher cell-type specificity under functional constraint. We conclude that the systematical use of histone modifications can differentiate non-expressed mRNAs from unstable mRNAs, and distinguish stable mRNAs from highly expressed ones. In summary, we represent the first computational model of mRNA stability inference that compares transcriptome and epigenome profiles, and provides an alternative strategy for directing experimental measurements.

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Digitale ISSN: 1362-4962

Thema: Biologie

Publiziert von Oxford University Press

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