The Generic Model Organism System Database Project (GMOD) seeks to develop reusable software components for model organism system databases. In this paper we describe the Generic Genome Browser ...(GBrowse), a Web-based application for displaying genomic annotations and other features. For the end user, features of the browser include the ability to scroll and zoom through arbitrary regions of a genome, to enter a region of the genome by searching for a landmark or performing a full text search of all features, and the ability to enable and disable tracks and change their relative order and appearance. The user can upload private annotations to view them in the context of the public ones, and publish those annotations to the community. For the data provider, features of the browser software include reliance on readily available open source components, simple installation, flexible configuration, and easy integration with other components of a model organism system Web site. GBrowse is freely available under an open source license. The software, its documentation, and support are available at http://www.gmod.org.
Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically ...driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
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•Hypoxic microenvironment is essential for propagation and growth of PFA ependymoma•Hypoxia controls metabolic intermediates that maintain an H3K27 hypomethylated genome•Inhibition or potentiation of histone lysine methylation diminishes PFA survival•Gliogenic lineage of developing fetal hindbrain mirrors PFA metabolic alterations
Hypoxia reprograms the cellular metabolome and epigenome to promote growth of the most lethal ependymomas.
Recent years have seen an explosion in the amount of available biological data. More and more genomes are being sequenced and annotated, and protein and gene interaction data are accumulating. ...Biological databases have been invaluable for managing these data and for making them accessible. Depending on the data that they contain, the databases fulfil different functions. But, although they are architecturally similar, so far their integration has proved problematic.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The HapMap Web site at http://www.hapmap.org is the primary portal to genotype data produced as part of the International Haplotype Map Project. In phase I of the project, >1.1 million SNPs were ...genotyped in 270 individuals from four worldwide populations. The HapMap Web site provides researchers with a number of tools that allow them to analyze the data as well as download data for local analyses. This paper presents step-by-step guides to using those tools, including guides for retrieving genotype and frequency data, picking tag-SNPs for use in association studies, viewing haplotypes graphically, and examining marker-to-marker LD patterns.
Background
Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been ...extensively explored for detection of recurrence in head and neck cancer.
Methods
Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient‐specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre‐treatment blood samples and longitudinally during standard follow‐up. Circulating tumor DNA status during follow‐up was correlated to disease recurrence.
Results
Samples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence.
Conclusion
Circulating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.
Caenorhabditis elegans mutants deleted for TDP‐1, an ortholog of the neurodegeneration‐associated RNA‐binding protein TDP‐43, display only mild phenotypes. Nevertheless, transcriptome sequencing ...revealed that many RNAs were altered in accumulation and/or processing in the mutant. Analysis of these transcriptional abnormalities demonstrates that a primary function of TDP‐1 is to limit formation or stability of double‐stranded RNA. Specifically, we found that deletion of tdp‐1: (1) preferentially alters the accumulation of RNAs with inherent double‐stranded structure (dsRNA); (2) increases the accumulation of nuclear dsRNA foci; (3) enhances the frequency of adenosine‐to‐inosine RNA editing; and (4) dramatically increases the amount of transcripts immunoprecipitable with a dsRNA‐specific antibody, including intronic sequences, RNAs with antisense overlap to another transcript, and transposons. We also show that TDP‐43 knockdown in human cells results in accumulation of dsRNA, indicating that suppression of dsRNA is a conserved function of TDP‐43 in mammals. Altered accumulation of structured RNA may account for some of the previously described molecular phenotypes (e.g., altered splicing) resulting from reduction of TDP‐43 function.
Synopsis
Mutations in RNA‐binding protein TDP‐43 are linked to ALS. This study reports that the worm homolog of TDP‐43, TDP‐1, limits the accumulation of double‐stranded RNAs, offering insight on the potential contribution of TDP‐43/TDP‐1 to disease onset.
TDP‐1 acts co‐transcriptionally to limit the accumulation of dsRNA
TDP‐1 limits A‐to‐I RNA editing
TDP‐1 maintains chemotaxis by limiting the action of RNA interference
Knockdown of TDP‐43 in human cells leads to an increase in dsRNA, potentially inducing an interferon response
Human TDP‐43 can act as an RNA chaperone in vitro
Mutations in RNA‐binding protein TDP‐43 are linked to ALS. This study reports that the worm homolog of TDP‐43, TDP‐1, limits the accumulation of double‐stranded RNAs, offering insight on the potential contribution of TDP‐43/TDP‐1 to disease onset.
Plant Reactome (http://plantreactome.gramene.org/) is a free, open-source, curated plant pathway database portal, provided as part of the Gramene project. The database provides intuitive ...bioinformatics tools for the visualization, analysis and interpretation of pathway knowledge to support genome annotation, genome analysis, modeling, systems biology, basic research and education. Plant Reactome employs the structural framework of a plant cell to show metabolic, transport, genetic, developmental and signaling pathways. We manually curate molecular details of pathways in these domains for reference species Oryza sativa (rice) supported by published literature and annotation of well-characterized genes. Two hundred twenty-two rice pathways, 1025 reactions associated with 1173 proteins, 907 small molecules and 256 literature references have been curated to date. These reference annotations were used to project pathways for 62 model, crop and evolutionarily significant plant species based on gene homology. Database users can search and browse various components of the database, visualize curated baseline expression of pathway-associated genes provided by the Expression Atlas and upload and analyze their Omics datasets. The database also offers data access via Application Programming Interfaces (APIs) and in various standardized pathway formats, such as SBML and BioPAX.
The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of ...Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.
The binding of PRDM9 to chromatin is a key step in the induction of DNA double-strand breaks associated with meiotic recombination hotspots; it is normally expressed solely in germ cells. We ...interrogated 1879 cancer samples in 39 different cancer types and found that
is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of
in tumors are significantly higher than those found in healthy neighboring tissues and in healthy nongerm tissue databases. Recurrently mutated regions located within 5 Mb of the
loci, as well as differentially expressed genes in meiotic pathways, correlate with
expression. In samples with aberrant
expression, structural variant breakpoints frequently neighbor the DNA motif recognized by PRDM9, and there is an enrichment of structural variants at sites of known meiotic PRDM9 activity. This study is the first to provide evidence of an association between aberrant expression of the meiosis-specific gene
with genomic instability in cancer.
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